[Based on 2013 PUBMED DATA]

some fascinating insights here ... detailed discussion to follow


Applied Research,Concepts, Heuristics, Systems, Innovation, Exploration

current initiatives







Meta-analyses are now widely used in medical/clinical research. It is interesting to speculate about what we can find from doing

an analysis (or meta-analysis) of meta-analysis. This is some initial raw data to get this area going ... we are starting with recent 2013 abstracts pulled from PUBMED ... other years will follow ... (thoughts? send a note)


(2013). "Association of all-cause mortality with overweight and obesity using standard body mass index categories. A systematic review and meta-analysis." Br Dent J 214(3): 113.

'...lower mortality among overweight and moderately obese patients' but higher mortality for those with a BMI >35.

(2013). "Early interventions to prevent psychosis: systematic review and meta-analysis." BMJ 346: f762.

(2013). "Elective high-frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants." Neonatology 103(1): 7-8; discussion 8-9.

BACKGROUND: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation in neonates with respiratory failure saves lives, its use is associated with lung injury and chronic lung disease (CLD). A newer form of ventilation called high-frequency oscillatory ventilation (HFOV) has been shown to result in less lung injury in experimental studies. OBJECTIVES: The objective of this review is to determine the effect of the elective use of HFOV as compared to conventional ventilation (CV) on the incidence of CLD, mortality and other complications associated with prematurity and assisted ventilation in preterm infants who are mechanically ventilated for respiratory distress syndrome (RDS). SEARCH METHODS: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross-references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in January 2009. SELECTION CRITERIA: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who required assisted ventilation. Randomization and commencement of treatment needed to be as soon as possible after the start of CV and usually in the first 12 h of life. DATA COLLECTION AND ANALYSIS: The methodological quality of each trial was independently reviewed by the various authors. The standard effect measures are relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat to produce one outcome were calculated. For all measures of effect, 95% confidence intervals were used. In subgroup analyses the 99% CIs are also given for summary RRs in the text. Meta-analysis was performed using a fixed effect model. Where heterogeneity was over 50%, the random effects RR is also given. MAIN RESULTS: Seventeen eligible studies of 3,652 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28-30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The effect of HFOV on CLD in survivors at term equivalent gestational age was inconsistent across studies and the reduction was of borderline significance overall. The effect was similar in trials with a high lung volume strategy for HFOV targeting at very low FiO(2) and trials with a high lung volume strategy with somewhat higher or unspecified target FiO(2). Subgroups of trials showed a significant reduction in CLD with HFOV when no surfactant was used, when piston oscillators were used for HFOV, when lung protective strategies for CV were not used, when randomization occurred at two to six hours of age, and when inspiratory:expiratory ratio of 1:2 was used for HFOV. In the meta-analysis of all trials, pulmonary air leaks occurred more frequently in the HFOV group. In some studies, short-term neurological morbidity with HFOV was found, but this effect was not statistically significant overall. The subgroup of two trials not using a high-volume strategy with HFOV found increased rates of grade 3 or 4 intraventricular hemorrhage and of periventricular leukomalacia. An adverse effect of HFOV on long-term neurodevelopment was found in one large trial but not in the five other trials that reported this outcome. The rate of retinopathy of prematurity is reduced overall in the HFOV group.

(2013). "Evaluation of the role of HTR1A C-1019G polymorphism in antidepressant efficacy: a meta-analysis." Pharmacogenomics 14(2): 130.

(2013). "Obesity and dental caries in children: a systematic review and meta-analysis." Br Dent J 214(3): 113.

There is an association between dental caries and obesity in children from industrialised countries but not from newly industrialised countries.

(2013). "Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis." BMJ 346: f903.

A, H., D. D, et al. (2013). "Clinicopathological characteristics of Posttransplant Lymphoproliferative Disorders of T-cell origin: single center series of 9 cases and meta-analysis of 147 reported cases." Leuk Lymphoma.

Abstract T-cell or natural killer (NK)-cell posttransplant lymphoproliferative disorder (T-PTLD) is a rare but severe complication after transplantation. Here we present the clinicopathological features of a single center series of 9 cases. Additionally, we summarize the clinicopathological findings of 147 T/NK-cell PTLDs reported in the literature in an attempt to define subtype-specific characteristics. T/NK-cell PTLD occurs in patients of all ages, usually extranodally, and most frequently after kidney transplantation. Organ specific incidence however is highest following heart transplantation. Approximately one third of T-cell PTLDs are Epstein-Barr virus (EBV)-related, with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) being the most prevalent EBV-associated T-cell PTLD. A male predominance was observed, which is most striking in the EBV (+) group, particularly in PTCL, NOS. With a median posttransplantation interval of 72 months T-cell PTLDs are among the late occurring PTLDs. Of the most common T-cell PTLDs, anaplastic large cell lymphoma (ALCL) has the best prognosis, whereas PTCL, NOS and hepatosplenic T-cell lymphoma (HSTCL) have the worst prognosis. EBV (+) cases seem to have a longer survival than EBV (-) cases, suggesting a different pathogenetic mechanism.

Abaci, A., S. Unlu, et al. (2013). "Short and long term complications of device closure of atrial septal defect and patent foramen ovale: Meta-analysis of 28,142 patients from 203 studies." Catheter Cardiovasc Interv.

Background. Device closure of atrial septal defect (ASD) and patent foramen ovale (PFO) are both associated with short- and long-term complications. Our knowledge of the complication rates of ASD and PFO closure is limited. Our objective was to review the peri-procedural and long-term complications of ASD and PFO closure. Methods. Medline, EMBASE, and Scopus databases were searched between 1973 and 2012. A total of 28142 patients from 203 case series were included. Of these 203 articles, 111 were reporting ASD closure, 61 were reporting PFO closure, and 31 were reporting both. Pooled incidence rates of cardiac complications were calculated separately for peri-procedural and at follow-up. Results. Peri-procedural major complications were reported from 0% to 9.4%, with a pooled estimate rate of 1.4% (95% CI: 1.3% to 1.6%). It was 1.6% (95% CI, 1.4-1.8) in ASD group, 1.1% (95% CI, 0.9-1.3) in PFO group, and 1.3% (95% CI, 0.9-1.9) in ASD/PFO group. The most common major complication was the device embolization requiring surgery. Peri-procedural minor complications were reported with a pooled estimate rate of 1.4% (95% CI, 1.2-1.7). It was 1.6% (95% CI, 1.2-2.1) in ASD group, 1.3% (95% CI, 1.0-1.7) in PFO group, and 1.5% (95% CI, 1.1-1.2.1) in ASD/PFO group. The most frequent major complications at follow-up were cerebrovascular events (1.3% (95% CI: 1.1% to 1.6%)) and device thrombosis (1.2% (95% CI: 1.0% to 1.4%)). Both were more frequent in PFO group. Conclusion. Device closure of ASD and PFO are associated with non-negligible serious complications, both in early and long-term. (c) 2013 Wiley Periodicals, Inc.

Abdelaal, E., S. V. Rao, et al. (2013). "Same-day discharge compared with overnight hospitalization after uncomplicated percutaneous coronary intervention: a systematic review and meta-analysis." JACC Cardiovasc Interv 6(2): 99-112.

OBJECTIVES: This study sought to evaluate outcomes of same-day discharge (SDD) following percutaneous coronary intervention (PCI) versus overnight hospitalization (ON). BACKGROUND: Although there are data on the safety and feasibility of SDD after PCI, ON continues to be prevalent. METHODS: The Cochrane search strategy was used to search the PubMed database, EMBASE, and the Cochrane Library for relevant literature. Thirteen studies (5 randomized and 8 observational) of SDD after uncomplicated PCI versus ON met inclusion criteria. Data were pooled using a random effects model, and reported as odds ratios (OR) with their 95% confidence intervals (CI). The primary outcomes were incidence of total complications, major adverse cardiovascular events (MACE), and rehospitalization within 30 days after PCI. RESULTS: A total of 13 studies, involving 111,830 patients were pooled. There was significant variation in the definition of outcomes across studies. For total complications, the strategy of SDD compared with ON after PCI had an estimated OR of 1.20 (95% CI: 0.82 to 1.74) in randomized and 0.67 (95% CI: 0.27 to 1.66) in observational studies. Similar results were found for MACE (randomized, OR: 0.99, 95% CI: 0.45 to 2.18; observational, OR: 0.59, 95% CI: 0.06 to 5.57) and rehospitalizations (randomized, OR: 1.10, 95% CI: 0.70 to 1.74; observational, OR: 0.62, 95% CI: 0.10 to 3.98) at 30 days post PCI. CONCLUSIONS: There is considerable heterogeneity across published studies comparing SDD with ON. This, coupled with the low event rate and wide corresponding CIs, suggest that an adequately powered multicenter randomized trial comparing SDD with ON would require a very large sample size (>17,000). Until such a trial is completed, SDD after uncomplicated PCI seems a reasonable approach in selected patients.

Abou-Setta, A. M., B. Houston, et al. (2013). "Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery." Cochrane Database Syst Rev 1: CD005072.

BACKGROUND: Various options exist for treating endometriosis, including surgical, medical, such as ovarian suppression, or a combination of these strategies. Surgical treatment of endometriosis aims to remove visible areas of endometriosis. The aim of medical therapy is to inhibit growth of endometriotic implants by induction of a hypo-estrogenic state. Treatment with a hormone-releasing intrauterine device, using levonorgestrel (LNG-IUD), has also been suggested. OBJECTIVES: To determine whether postoperative LNG-IUD insertion in women with endometriosis improves pain and reduces recurrence of symptoms compared with no postoperative treatment, postoperative insertion of a placebo, or postoperative therapy. SEARCH METHODS: The following databases were searched from inception to June 2012: Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, CINAHL, and the World Health Organization (WHO) International Clinical Trials Registry Platform. EMBASE was searched from 2010 to June 2012. The citation lists of relevant publications, review articles, abstracts of scientific meetings, and included studies were also searched. SELECTION CRITERIA: Trials were included if they compared women undergoing surgical treatment for endometriosis with uterine preservation and then randomised within three months to LNG-IUD insertion versus no postoperative treatment, placebo (inert IUD), or other treatment. Diagnostic laparoscopy alone was not considered suitable treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted data to allow for an intention-to-treat analysis. For dichotomous data, the risk ratio (RR) and 95% confidence interval (CI) were calculated using the Mantel-Haenszel random-effects method. For continuous data, the mean difference (MD) and 95% CI were calculated using the inverse variance random-effects method. MAIN RESULTS: Three randomised controlled trials were included. In two trials, there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUD group compared with expectant management (RR 0.22, 95% CI 0.08 to 0.60, 95 women, I(2) = 0%, moderate strength of evidence). The proportion of women who were satisfied with their treatment was also higher in the LNG-IUD group but did not reach statistical significance (RR 1.21, 95% CI 0.80 to 1.82, 95 women, I(2) = 0%). The number of women reporting a change in menstruation was significantly higher in the LNG-IUD group (RR 37.80, 95% CI 5.40 to 264.60, 95 women, I(2) = 0%) but the number of women not completing the allocated treatment did not differ between groups (RR 0.66, 95% CI 0.08 to 5.25, I(2) = 43%).In one trial, women receiving LNG-IUD noted lower pain scores compared with women receiving gonadotrophin-releasing hormone agonists (MD -0.16, 95% CI -2.02 to 1.70, 40 women) but this did not reach statistical significance. AUTHORS' CONCLUSIONS: There is limited but consistent evidence showing that postoperative LNG-IUD use reduces the recurrence of painful periods in women with endometriosis. Further well-designed RCTs are needed to confirm these findings.

Abozaid, S. M., M. Shoukri, et al. (2013). "Prevailing genotypes of hepatitis C virus in Saudi Arabia: a systematic analysis of evidence." Ann Saudi Med 33(1): 1-5.

BACKGROUND AND OBJECTIVES: Although hepatitis C virus (HCV) genotype 4 has been reported to be prevalent in some countries of the Middle East, the genotype distribution in some geographical areas is not conclusive. We aimed to perform a meta-analysis on available literature on this issue in an attempt to identify or confirm the prevailing HCV genotypes in Saudi Arabia. METHODS: We searched for reports describing genotypes in Saudi Arabia. A meta-analysis was performed on the samples in 18 studies, published between 1995 and 2011, in which HCV genotypes were identified. RESULTS: A total of 2277 specimens from 18 studies showed that 617, 82, 119 and 1198 subjects were HCV-positive for genotypes 1, 2, 3 and 4, respectively. The meta-analyses showed that there is a great deal of heterogeneity in estimated prevalence among the studies. The highest prevalence was found in genotype HCV-4, followed by HCV-1, HCV-3, and HCV-2. CONCLUSION: Our meta-analysei emphasizes that HCV genotype 4 is the most prevalent, followed by genotype 1. Further studies on genotype determination and subtype distribution are warranted.

Abramovici, A. and S. Jenkins (2013). "Network meta-analysis shows that prostaglandin inhibitors and nifedipine are best short-term tocolytics for preterm delivery." Evid Based Med.

Achana, F. A., N. J. Cooper, et al. (2013). "Extending methods for investigating the relationship between treatment effect and baseline risk from pairwise meta-analysis to network meta-analysis." Stat Med 32(5): 752-71.

Baseline risk is a proxy for unmeasured but important patient-level characteristics, which may be modifiers of treatment effect, and is a potential source of heterogeneity in meta-analysis. Models adjusting for baseline risk have been developed for pairwise meta-analysis using the observed event rate in the placebo arm and taking into account the measurement error in the covariate to ensure that an unbiased estimate of the relationship is obtained. Our objective is to extend these methods to network meta-analysis where it is of interest to adjust for baseline imbalances in the non-intervention group event rate to reduce both heterogeneity and possibly inconsistency. This objective is complicated in network meta-analysis by this covariate being sometimes missing, because of the fact that not all studies in a network may have a non-active intervention arm. A random-effects meta-regression model allowing for inclusion of multi-arm trials and trials without a 'non-intervention' arm is developed. Analyses are conducted within a Bayesian framework using the WinBUGS software. The method is illustrated using two examples: (i) interventions to promote functional smoke alarm ownership by households with children and (ii) analgesics to reduce post-operative morphine consumption following a major surgery. The results showed no evidence of baseline effect in the smoke alarm example, but the analgesics example shows that the adjustment can greatly reduce heterogeneity and improve overall model fit. Copyright (c) 2012 John Wiley & Sons, Ltd.

Adams, S. T., M. Salhab, et al. (2013). "Roux-en-Y gastric bypass for morbid obesity: what are the preoperative predictors of weight loss?" Postgrad Med J.

Obesity has become an increasingly important health problem over the past 30 years. Presently around a quarter of the UK adult population are obese and this figure is set to increase further in the coming decades. The health consequences of obesity on multiple body systems have been well established as has the financial cost of the condition to both the individuals affected as well as to society as a whole. Bariatric surgery has been shown to be the only long term effective solution in terms of sustained weight loss and comorbidity resolution. The commonest bariatric procedure in the UK is the Roux-en-y gastric bypass which consistently results in the loss of 70%-80% of excess bodyweight. Results however are variable and in order to optimise resource allocation and avoid exposing patients unlikely to benefit from surgery to its inherent risks, much research has been done to try to identify those patients most likely to obtain a good result. The only factor which has been subjected to meta-analysis is that of preoperative weight loss which shows a positive association with postoperative weight loss following bypass surgery. Although the remaining data are not based on level 1 evidence those other preoperatively identifiable factors which are associated with an improved outcome include Caucasian or Hispanic ethnicity, higher educational status, non-shift-work working patterns, female gender and divorced or single marital status. Similarly increased levels of preoperative physical activity and an absence of binge eating behaviour are consistent with a favourable result whereas increased age, smoking and other socioeconomic factors have not been shown to have a significant impact. Conversely diabetes mellitus seems to have a slight negative correlation with postoperative weight loss; however, a history of sexual abuse or psychiatric illness has not been shown to have a lasting influence.

Adams, V., B. Mathisen, et al. (2013). "A Systematic Review and Meta-analysis of Measurements of Tongue and Hand Strength and Endurance Using the Iowa Oral Performance Instrument (IOPI)." Dysphagia.

The purpose of this systematic review was to examine the evidence for the use of the Iowa Oral Performance Instrument (IOPI) to measure strength and endurance of the tongue and hand in healthy populations and those with medical conditions. A systematic search of the scientific literature published since 1991 yielded 38 studies that addressed this purpose. The IOPI was used primarily for tongue strength (38 studies) and endurance (15 studies) measurement; relatively few studies measured hand strength (9 studies) or endurance (6 studies). The majority of the studies identified used the IOPI as an evaluation tool, although four used it as an intervention tool. Half the studies were conducted in healthy people, primarily adults. Most of the other participants had disorders with dysphagia, primarily Parkinson's disease or head or neck cancer. Age and gender, as well as a number of medical conditions, influence the values of tongue and hand strength. There is sufficient evidence to support the use of the IOPI as a suitable tool for measuring tongue strength and endurance and as an assessment tool for intervention studies, and there is growing support for its use to assess hand strength and endurance in healthy and clinical populations.

Agathokleous, M., P. Chaveeva, et al. (2013). "Meta-analysis of second-trimester markers for trisomy 21." Ultrasound Obstet Gynecol 41(3): 247-61.

OBJECTIVE: To summarize by meta-analysis the accumulated data on the screening performance of second-trimester sonographic markers for fetal trisomy 21. METHODS: We conducted a literature search to identify studies between 1995 and September 2012 that provided data on the incidence of sonographic markers in trisomy 21 and euploid fetuses at 14-24 weeks' gestation. Weighted independent estimates of detection rate, false-positive rate and positive and negative likelihood ratios (LR) of markers were calculated. RESULTS: A total of 48 studies was included in the analysis. The pooled estimates of positive and negative LR were, respectively: 5.83 (95% CI, 5.02-6.77) and 0.80 (95% CI, 0.75-0.86) for intracardiac echogenic focus; 27.52 (95% CI, 13.61-55.68) and 0.94 (95% CI, 0.91-0.98) for ventriculomegaly; 23.30 (95% CI, 14.35-37.83) and 0.80 (95% CI, 0.74-0.85) for increased nuchal fold; 11.44 (95% CI, 9.05-14.47) and 0.90 (95% CI, 0.86-0.94) for hyperechogenic bowel; 7.63 (95% CI, 6.11-9.51) and 0.92 (95% CI, 0.89-0.96) for mild hydronephrosis; 3.72 (95% CI, 2.79-4.97) and 0.80 (95% CI, 0.73-0.88) for short femur; 4.81 (95% CI, 3.49-6.62) and 0.74 (95% CI, 0.63-0.88) for short humerus; 21.48 (95% CI, 11.48-40.19) and 0.71 (95% CI, 0.57-0.88) for aberrant right subclavian artery (ARSA); and 23.27 (95% CI, 14.23-38.06) and 0.46 (95% CI, 0.36-0.58) for absent or hypoplastic nasal bone. The combined negative LR, obtained by multiplying the values of individual markers, was 0.13 (95% CI, 0.05-0.29) when short femur but not short humerus was included and 0.12 (95% CI, 0.06-0.29) when short humerus but not short femur was included. CONCLUSION: The presence of sonographic markers increases, and absence of such markers decreases, the risk for trisomy 21. In the case of most isolated markers there is only a small effect on modifying the pre-test odds for trisomy 21, but with ventriculomegaly, nuchal fold thickness and ARSA there is a 3-4-fold increase in risk and with hypoplastic nasal bone a 6-7-fold increase. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Aguilera, I., M. Pedersen, et al. (2013). "Early-Life Exposure to Outdoor Air Pollution and Respiratory Health, Ear Infections, and Eczema in Infants from the INMA Study." Environ Health Perspect 121(3): 387-92.

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health.Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12-18 months of age in a Spanish birth cohort of 2,199 infants.Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO2) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations.Results: A 10-microg/m3 increase in average NO2 during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO2 were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO2, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period.Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.

Aguirre, E., R. T. Woods, et al. (2013). "Cognitive stimulation for dementia: a systematic review of the evidence of effectiveness from randomised controlled trials." Ageing Res Rev 12(1): 253-62.

Cognitive stimulation is a psychological intervention widely used in dementia care, which offers a range of activities for people with dementia and provides general stimulation of cognitive abilities. This systematic review evaluates the effectiveness of cognitive stimulation in dementia. The review included studies from the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, called ALOIS. This yielded ninety-four studies, of which fifteen were randomised controlled trials meeting the inclusion criteria. The analysis included 718 subjects (407 receiving cognitive stimulation and 311 in control groups). Results were subjected to a meta-analysis. A consistent significant benefit to cognitive function was identified following treatment and the benefits appeared to be over and above any medication effects. This remained evident at follow-up up to three months after the end of treatment. In secondary analyses, with smaller total sample sizes, significant benefits were also noted for quality of life and well-being, and on staff ratings of communication and social interaction. No differences in relation to mood, activities of daily living or challenging behaviour were noted. There is consistent evidence that cognitive stimulation interventions benefit cognitive function and aspects of well-being. Cognitive stimulation should be made more widely available in dementia care.

Ahmad Kiadaliri, A., J. Jarl, et al. (2013). "Alcohol drinking cessation and the risk of laryngeal and pharyngeal cancers: a systematic review and meta-analysis." PLoS One 8(3): e58158.

OBJECTIVE: To evaluate the effect of alcohol cessation on the risk of developing laryngeal and pharyngeal cancers, combining available evidence in the scientific literature in a meta-analysis. METHODS: A systematic literature review was conducted, and a meta-analysis was applied on the retrieved studies. The generalised least squares method was used to estimate the trend from dose-response data to assess changes in the risks of laryngeal and pharyngeal cancers after drinking cessation. RESULTS: A total of 9 case-control studies were included in the meta-analysis (4 and 8 estimates for laryngeal and pharyngeal cancers, respectively). On average, alcohol drinking cessation was associated with a 2% yearly reduction in the risk of developing laryngeal and pharyngeal cancers. There was a considerable heterogeneity between the studies of pharyngeal cancer, but this was mostly due to two studies. The increased risk of laryngeal and pharyngeal cancers caused by alcohol was reversible; the time periods until the risks became equal to those of never drinkers were 36 (95% CI 11-106) and 39 (95% CI 13-103) years, respectively. Moreover, 5 years of drinking cessation was associated with a reduction of around 15% in the alcohol-related elevated risk of laryngeal and pharyngeal cancers. CONCLUSION: Although a long time period is required to completely eliminate the alcohol-related elevated risk of laryngeal and pharyngeal cancers, a substantial risk reduction can be seen in the short term (5-10 years), and drinking cessation should therefore be encouraged to reduce the incidence of these cancers.

Ahmadi, H. and S. Daneshmand (2013). "Androgen deprivation therapy: evidence-based management of side effects." BJU Int.

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The benefits of androgen deprivation therapy (ADT) are well recognized and a multitude of studies have documented the benefits of ADT in conjunction with other therapies. Given the widespread use of ADT due to its important clinical implications, it is imperative that clinicians understand the side effects to limit treatment-related morbidity. There are numerous well recognized adverse effects of ADT, including vasomotor flushing, loss of libido and impotence, fatigue, gynaecomastia, anaemia, osteoporosis and metabolic complications, as well as effects on cardiovascular health and bone density. Present study focuses on the most recent evidence-based treatment options for various side effects of ADT. OBJECTIVE: To familiarize clinicians with the various side effects of androgen deprivation therapy (ADT). The present study focuses on the most recent evidence-based treatment strategies for the common side effects of ADT. METHODS: A PubMed database search was conducted from 2000 to 2012. All prospective clinical studies were selected, including randomized and non-randomized clinical trials, as well as meta-analysis studies concerning preventive and therapeutic interventions for various side effects of ADT. 'The Oxford 2011 Levels of Evidence' classification system for treatment benefits was used to categorize selected studies. RESULTS: Gabapentin shows moderate efficacy for the long-term treatment of hot flashes in a dose-dependent manner. A combined resistance/aerobic exercise programme leads to significant improvement in fatigue, sexual function and cognitive function. A home-based/group exercise programme also improves fatigue and unfavourable metabolic changes. Denosumab increases lumbar spine, hip and radius bone mass density, and also reduces the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Metformin coupled with lifestyle intervention is a safe, well-tolerated intervention for adverse metabolic changes. Toremifene improves the lipid profile. Intermittent ADT improves early side effects, such as hot flashes, sexual activity, fatigue, and quality of life, although its effect on long-term side effects remains inconclusive. CONCLUSION: Despite significant improvement in management strategies for the side effects of ADT, the best way of preventing side effects is to use ADT only when it is absolutely indicated.

Ahmed, K., H. Ashrafian, et al. (2013). "Safety of training and assessment in operating theatres--a systematic review and meta-analysis." Perfusion 28(1): 76-87.

OBJECTIVE: Procedural outcomes can be used to assess the performance of specialists and trainees. This article establishes a systematic evidence base for the safety of training in the operating theatre. It also explores the possibility of using early, intermediate and late procedural outcomes of cardiac surgical operations to evaluate the performance of the clinicians and the healthcare system. METHODS: Medline, EMBASE and PsycINFO databases were searched. Comparative studies evaluating quality indicators of cardiac surgical procedures (coronary artery bypass grafting (CABG) and valve surgery) were included. guidelines from the preferred reporting items for systematic reviews and meta-analyses (PRISMA) were used. RESULTS: Fourteen studies met the inclusion criteria. For CABG, meta-analysis of outcomes did not show any significant differences between the technical and non-technical skills of trainees versus specialists apart from bypass time (less for specialists) and intensive care unit (ICU) length of stay (less for trainees). Studies reporting outcomes on valve surgery also did not report any statistically significant differences amongst the outcomes. CONCLUSION: This systematic review did not discern any significant differences between the procedural outcomes of trainees and specialists, which indicates that trainees are safe to operate under senior supervision. In addition, this article recommends that various procedural outcomes can be used to evaluate the performance of clinicians and healthcare systems. Prospective studies need to be performed, taking into account the specific contribution of trainees and specialists during the procedure. This will give a clearer indication of safety and performance of trainees and specialists in the operating theatre.

Ajala, O., P. English, et al. (2013). "Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes." Am J Clin Nutr 97(3): 505-16.

BACKGROUND: There is evidence that reducing blood glucose concentrations, inducing weight loss, and improving the lipid profile reduces cardiovascular risk in people with type 2 diabetes. OBJECTIVE: We assessed the effect of various diets on glycemic control, lipids, and weight loss. DESIGN: We conducted searches of PubMed, Embase, and Google Scholar to August 2011. We included randomized controlled trials (RCTs) with interventions that lasted >/=6 mo that compared low-carbohydrate, vegetarian, vegan, low-glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets. RESULTS: A total of 20 RCTs were included (n = 3073 included in final analyses across 3460 randomly assigned individuals). The low-carbohydrate, low-GI, Mediterranean, and high-protein diets all led to a greater improvement in glycemic control [glycated hemoglobin reductions of -0.12% (P = 0.04), -0.14% (P = 0.008), -0.47% (P < 0.00001), and -0.28% (P < 0.00001), respectively] compared with their respective control diets, with the largest effect size seen in the Mediterranean diet. Low-carbohydrate and Mediterranean diets led to greater weight loss [-0.69 kg (P = 0.21) and -1.84 kg (P < 0.00001), respectively], with an increase in HDL seen in all diets except the high-protein diet. CONCLUSION: Low-carbohydrate, low-GI, Mediterranean, and high-protein diets are effective in improving various markers of cardiovascular risk in people with diabetes and should be considered in the overall strategy of diabetes management.

Akbar, A., B. K. Abu Dayyeh, et al. (2013). "Rectal NSAIDs are Superior to Pancreatic Duct Stents in Preventing Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography: A Network Meta-Analysis." Clin Gastroenterol Hepatol.

BACKGROUND & AIMS: Placement of pancreatic duct stents prevents pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). There is evidence that rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) also prevents post-ERCP pancreatitis, but the 2 approaches alone have not been compared directly. We conducted a network meta-analysis to indirectly compare the efficacies of these procedures. METHODS: PubMed and Embase were searched by 2 independent reviewers to identify full-length clinical studies, published in English, investigating use of pancreatic duct stent placement and rectal NSAIDs to prevent post-ERCP pancreatitis. We identified 29 studies (22 of pancreatic duct stents and 7 of NSAIDs). We used network meta-analysis to compare rates of post-ERCP pancreatitis among patients that received only rectal NSAIDs, only pancreatic duct stents, or both. RESULTS: Placement of pancreatic duct stents and rectal administration of NSAIDs were each superior to placebo in preventing post-ERCP pancreatitis. The combination of rectal NSAIDs and stents was not superior to either approach alone. Pooled results showed that rectal NSAIDs alone were superior to pancreatic duct stents alone in preventing PEP (odds ratio, 0.48; 95% confidence interval, 0.26-0.87). CONCLUSIONS: Based on a network meta-analysis, rectal NSAIDs alone are superior to PD stents alone in preventing post-ERCP pancreatitis, and should be considered first-line therapy for selected patients. However, these findings are limited by the small number of studies assessed (29), potential publication bias, and the indirect nature of the comparison. High-quality randomized controlled trials are needed to compare these 2 interventions and confirm these findings.

Akbari, M., S. Shah, et al. (2013). "Systematic Review and Meta-analysis on the Effects of Thiopurines on Birth Outcomes from Female and Male Patients with Inflammatory Bowel Disease." Inflamm Bowel Dis 19(1): 15-22.

BACKGROUND: : Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD. METHODS: : A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities. RESULTS: : In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25). CONCLUSIONS: : Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

Akhtar, S. (2013). "Areca nut chewing and esophageal squamous-cell carcinoma risk in Asians: a meta-analysis of case-control studies." Cancer Causes Control 24(2): 257-65.

PURPOSE: This meta-anlaysis quantitatively assessed an overall independent association between areca nut chewing and esophageal squamous-cell carcinoma in Asians. METHODS: Studies (case-control and/or cohort) were identified by searching the PubMed, Medline, and Embase databases through 30 September, 2012, using the keywords o/esophageal squamous-cell carcinoma, o/esophageal cancer, chewing areca nut, betel quid without tobacco, Asia, and the reference lists of retrieved articles. Random-effects model was used to compute adjusted summary OR(RE) for the main effect of areca nut chewing and additive (biological) interaction between areca nut chewing and tobacco smoking along with their corresponding 95 % confidence intervals (CI). To quantify the impact of between-study heterogeneity on adjusted main-effect summary OR(RE), Higgins' H and I (2) statistics along with their 95 % uncertainty intervals were used. Funnel plot and Egger's test were used to evaluate publication bias. RESULTS: Meta-analysis of 12 case-control studies (2,836 cases; 9,553 controls) showed that areca nut chewing was significantly and independently associated with an increased risk of esophageal squamous-cell carcinoma (adjusted main-effect summary OR(RE) = 3.05; 95 % CI 2.41, 3.87). Furthermore, pooled analysis of additive interaction between areca nut chewing and tobacco smoking reported by six of the included studies revealed manifold increased risk of esophageal squamous-cell carcinoma among those who indulged in both the practices compared with those who practiced none (adjusted additive interaction-effect summary OR(RE) = 6.79; 95 % CI 4.71, 9.79). There was no significant publication bias (p = 0.289). CONCLUSIONS: Areca nut chewing was significantly and independently associated with an increased risk of esophageal squamous-cell carcinoma in Asians. Additionally, individuals who indulged in both areca nut chewing and tobacco smoking had manifold increased risk of esophageal squamous-cell carcinoma. The efforts aimed at curtailing the addiction to areca nut chewing may contribute to lower the incidence of esophageal squamous-cell carcinoma and related mortality in Asians.

Akin, S., T. Yetgin, et al. (2013). "Effect of collaterals on deaths and re-infarctions in patients with coronary artery disease: a meta-analysis." Neth Heart J 21(3): 146-51.

BACKGROUND: It is generally believed that there is a beneficial effect of collaterals on death and re-infarction statistics in patients with coronary artery disease (CAD) but studies to date are small and inconsistent. OBJECTIVE: To meta-analyse the studies published in this field in order to obtain more powerful information. METHODS: We searched Medline and major journals (2000 to 2011) for studies evaluating the effect of coronary collaterals on mortality. Publication bias, lack of heterogeneity, and lack of robustness were assessed using the standard procedures for such purposes. RESULTS: A total of 10 studies describing mortality, enrolling 6791 participants, were included in this analysis. In patients with collateralisation a significant relation with reduced mortality was seen compared with those without collateralisation, at an odds ratio of 0.47, p < 0.0001, and a reduction in deaths and re-infarctions at 0.54, p < 0.0001. Some publication bias, some heterogeneity and some lack of robustness were demonstrated. A meta-regression with the odds ratios of the presence of traditional atherosclerotic risk factors as predictors and the odds ratios of mortality and the composite deaths and re-infarctions as outcome showed no relationships. CONCLUSIONS: In CAD patients from the post-percutaneous coronary intervention era the presence of collaterals reduced mortality by 0.47 (p < 0.0001) and deaths and re-infarctions by 0.54 (p < 0.0001). Furthermore, in the present meta-data, the atherosclerotic risk factors were no more present in patients with collaterals than they were in those without.

Akin, Y. and S. Yucel (2013). "Is avocado a real expulsive therapy in ureterolithiasis?" J Endourol.

At the 30thWorld Congress of Endourology, dietary supplement with terpene compound drug (avocado) as an expulsive therapy for ureterolithiasis came into question again. Chua et al presented a meta-analysis of "terpene compound drug as medical expulsive therapy for ureterolithiasis".1 Additionally, recently published study by Ortiz-Alvarado et al supports dietary supplements on urinary stones.2,3 However, there is information regarding side effects or precautions on phytotherapy alternatives.

Akl, E. A., B. C. Johnston, et al. (2013). "Addressing dichotomous data for participants excluded from trial analysis: a guide for systematic reviewers." PLoS One 8(2): e57132.

INTRODUCTION: Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data. OBJECTIVE: The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials. METHODS: This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered 'non-adherent to the protocol' but for whom data are available, and participants with missing data. RESULTS: Systematic reviewer authors should include data from 'non-adherent' participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events. CONCLUSIONS: This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.

Al Rawahi, T., A. D. Lopes, et al. (2013). "Surgical cytoreduction for recurrent epithelial ovarian cancer." Cochrane Database Syst Rev 2: CD008765.

BACKGROUND: The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival. OBJECTIVES: To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly. SELECTION CRITERIA: Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm. DATA COLLECTION AND ANALYSIS: Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. MAIN RESULTS: There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.Adverse events, quality of life and cost-effectiveness were not reported in any of the studies. AUTHORS' CONCLUSIONS: In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

Al-Abbad, H. and J. V. Simon (2013). "The effectiveness of extracorporeal shock wave therapy on chronic achilles tendinopathy: a systematic review." Foot Ankle Int 34(1): 33-41.

BACKGROUND: Achilles tendinopathy is a pathological state resulting from repetitive loading or stress on the tendon. Extracorporeal shock wave therapy (ESWT) is hypothesized to be an effective alternative intervention to surgery when other conservative therapies fail. This systematic review investigated the effectiveness of ESWT in the treatment of insertional and noninsertional Achilles tendinopathies. METHODS: Articles were electronically searched from the Cochrane Controlled Trials Register, MEDLINE, CINAHL, EMBASE, and SPORTDiscus using a comprehensive search strategy. Studies were included if they were prospective clinical trials examining the effectiveness of ESWT for insertional or noninsertional Achilles tendinopathies. Methodological quality of included studies was assessed using PEDro scale and Modified McMaster tool. The strength of the evidence was reported using the National Health and Medical Research Council body of evidence framework. A narrative summary of the findings was presented. RESULTS: Four of the included studies were randomized controlled trials, and 2 were pre-post study designs. Common methodological deficiencies included not blinding the clinician and participants. There was consistent evidence from 4 reviewed studies on the effectiveness of ESWT in the management of patients with chronic Achilles tendinopathies at a minimum 3 months' follow-up. CONCLUSION: Overall, our review showed satisfactory evidence for the effectiveness of low-energy ESWT in the treatment of chronic insertional and noninsertional Achilles tendinopathies at a minimum 3 months' follow-up before considering surgery if other conservative management fails. However, combining ESWT with eccentric loading appears to show superior results. LEVEL OF EVIDENCE: Level 1, systematic meta-analysis.

Aladro-Gonzalvo, A. R., G. A. Araya-Vargas, et al. (2013). "Pilates-based exercise for persistent, non-specific low back pain and associated functional disability: a meta-analysis with meta-regression." J Bodyw Mov Ther 17(1): 125-36.

OBJECTIVE: The purposes of this study were to systematically review and apply regression analysis to randomised controlled trials [RCTs] that evaluated the effectiveness of Pilates exercise in improving persistent, non-specific low back pain and functional disability. METHODS: Electronic databases were searched from January 1950 to March 2011. Articles were eligible for inclusion if they were RCTs comparing Pilates exercise with a placebo treatment [PT], minimal intervention [MI] or another physiotherapeutic treatment [APT]. RESULTS: Nine trials were included. Pilates was moderately superior to APT (pooled Effect Size [ES] weighted = -0.55, 95% confidence interval [CI] = -0.08 to -1.03) in reducing disability but not for pain relief. Pilates provided moderate to superior pain relief compared to MI (pooled ES weighted = -0.44, 95% CI = -0.09 to -0.80) and a similar decrease in disability. The statistical model used did not detect any predictor variable. CONCLUSIONS: Due to the presence of co-interventions and the low methodological quality of some studies, these conclusions should be interpreted with caution.

Alam, M., H. D. Huang, et al. (2013). "Percutaneous coronary intervention vs. coronary artery bypass graft surgery for unprotected left main coronary artery disease in the drug-eluting stents era--an aggregate data meta-analysis of 11,148 patients." Circ J 77(2): 372-82.

BACKGROUND: Patients with unprotected left main coronary artery (LMCA) disease are increasingly treated with percutaneous coronary intervention (PCI) using drug-eluting stents (DES), but its benefits compared with coronary artery bypass grafting (CABG) remain controversial. We hypothesized that PCI with DES for unprotected LMCA disease is safe and effective compared with CABG. METHODS AND RESULTS: We performed aggregate data meta-analyses of clinical outcomes [death; non-fatal myocardial infarction (MI); stroke; repeat revascularization; and major adverse cardiac and cerebrovascular events (MACCE)] in studies comparing PCI with DES vs. CABG in patients with LMCA disease. A comprehensive literature search (01/01/2003 to 12/01/2011) identified 27 studies comparing PCI and CABG (11,148 patients). Summary odds ratios (OR) were calculated using a random-effects model. At 30 days, PCI for unprotected LMCA disease was associated with lower MACCE [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.36-0.89) and stroke rates (OR 0.22, 95% CI 0.11-0.44) compared with CABG. At 12 months, the PCI group experienced higher rates of repeat revascularization (OR 3.72, 95% CI 2.75-5.03), but lower rates of stroke (OR 0.25, 95% CI 0.14-0.44) and all-cause death (OR 0.69, 95% CI 0.49-0.97). At the longest follow-up of 60 months, PCI was associated with equivalent mortality, lower rates of stroke (OR 0.42, 95% CI 0.28-0.62) and higher rates of MACCE (OR 1.30, 95% CI 1.10-1.55) and repeat revascularization (OR 3.54, 95% CI 2.75-4.54). CONCLUSIONS: In the DES era, PCI for unprotected LMCA disease is associated with equivalent mortality and MI, lower stroke rates and higher rates of repeat revascularization compared with CABG.

Albanna, A. S., B. M. Smith, et al. (2013). "Fixed dose combination anti-tuberculosis therapy: a systematic review and meta-analysis." Eur Respir J.

Fixed-dose combination (FDC) formulations are currently recommended for treatment of active tuberculosis. We have conducted a systematic review to evaluate the risk of treatment failure or disease relapse, acquired drug resistance, bacterial conversion after two months of treatment, adverse events, adherence, and treatment satisfaction associated with treatment of active tuberculosis using FDC or separate drug formulations.We searched four electronic databases for randomized controlled trials and cohort studies. Results from trials that directly compared FDC to separate drug formulations were pooled. Results from other studies were reported separately.We identified 2450 citations from which 15 controlled trials and four additional relevant studies were included. In the 15 trials there were no differences in acquired drug resistance, bacterial conversion after two months of treatment, or adverse drug reactions with FDC or separate drug formulations. There was a trend toward higher risk of failure or relapse with FDC (pooled RR, 1.28 [95% CI: 0.99, 1.7]). Based on individual study results, only one of two trials that assessed treatment satisfaction, and none of five that assessed patient adherence favored FDC's.Although FDC formulations simplify tuberculosis therapy, the current evidence does not indicate that these formulations improve treatment outcomes among patients with active tuberculosis.

Albergotti, W. G., S. A. Nguyen, et al. (2013). "In response to extracapsular dissection for benign parotid tumors: A meta-analysis." Laryngoscope.

Alberts, N. M., H. D. Hadjistavropoulos, et al. (2013). "The Short Health Anxiety Inventory: A systematic review and meta-analysis." J Anxiety Disord 27(1): 68-78.

INTRODUCTION: The Short Health Anxiety Inventory (SHAI) measures health anxiety in medical and non-medical contexts. OBJECTIVE: To review the literature pertaining to the psychometric properties of the SHAI in non-clinical, clinical, and medical samples. Meta-analysis was also conducted to examine the strength of associations between the SHAI and other constructs. METHODS: Direct search of digital databases for papers that cited the original SHAI publication. RESULTS: Seventy-eight papers were identified, with 42 providing relevant information. The SHAI has acceptable Cronbach's alpha scores, strong construct validity, and is sensitive to treatment. Discrepancies have been observed between the findings of factor analytic studies, largely as a result of varying methods used. Overall, there appears to be greatest support for the original two factors, with one factor assessing health anxiety and one factor assessing negative consequences of illness. As expected, individuals with hypochondriasis score higher as compared to non-clinical samples. The strongest association was observed between the SHAI and other measures of health anxiety, followed by measures related to health anxiety vulnerability, and then general anxiety and worry. CONCLUSIONS: The SHAI is a psychometrically sound tool for assessing health anxiety across samples. Future studies are needed, however, to assess test-retest reliability, incremental validity, and cut-off scores as well as use of the SHAI among diverse samples.

Albertsen, H. M., R. Chettier, et al. (2013). "Genome-wide association study link novel Loci to endometriosis." PLoS One 8(3): e58257.

Endometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endometriosis is, on average, delayed by 7-10 years from the onset of symptoms. Absence of a timely and non-invasive diagnostic tool is presently the greatest barrier to the identification and treatment of endometriosis. Twin and family studies have documented an increased relative risk in families. To identify genetic factors that contribute to endometriosis we conducted a two-stage genome-wide association study (GWAS) of a European cohort including 2,019 surgically confirmed endometriosis cases and 14,471 controls. Three of the SNPs we identify associated at P<5x10 in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P = 8.65x10, OR = 1.29, CI = 1.18-1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P = 4.70x10, OR = 1.20, Cl = 1.13-1.29, and rs6757804; P = 4.05x10, OR = 1.20, Cl = 1.13-1.29). Using an adjusted Bonferoni significance threshold of 4.51x10 we identify two additional loci in our meta-analysis that associate with endometriosis:, RNF144B-ID4 on 6p22.3 (rs6907340; P = 2.19x10, OR = 1.20, Cl = 1.12-1.28), and HNRNPA3P1-LOC100130539 on 10q11.21 (rs10508881; P = 4.08x10, OR = 1.19, Cl = 1.11-1.27). Consistent with previously suggested associations to WNT4 our study implicate a 150 kb region around WNT4 that also include LINC00339 and CDC42. A univariate analysis of documented infertility, age at menarche, and family history did not show allelic association with these SNP markers. Clinical data from patients in our study reveal an average delay in diagnosis of 8.4 years and confirm a strong correlation between endometriosis severity and infertility (n = 1182, P<0.001, OR = 2.18). This GWAS of endometriosis was conducted with high diagnostic certainty in cases, and with stringent handling of population substructure. Our findings broaden the understanding of the genetic factors that play a role in endometriosis.

Albertsen, I. E., L. H. Rasmussen, et al. (2013). "Risk of Stroke or Systemic Embolism in Atrial Fibrillation Patients Treated With Warfarin: A Systematic Review and Meta-analysis." Stroke.

BACKGROUND AND PURPOSE: Although oral anticoagulants (OACs) are highly effective in reducing stroke risk in atrial fibrillation, some patients still sustain stroke despite being on an OAC. Our aim was to identify the risk factors that contribute to stroke risk in atrial fibrillation, although patients were taking OACs in a clinical trial setting. METHODS: We identified contemporary clinical trials that investigated OACs in patients with atrial fibrillation. Event rates per year from each study and pooled event rates and relative risks, all with a 95% confidence interval, were calculated. Statistical heterogeneity was assessed using the I2 test. RESULTS: Six trials were included in the meta-analysis, with a total of 58 883 patients randomized. Characteristics associated with a higher relative risk of stroke while on an OAC included age >/=75 years (relative risk, 1.46 [95% confidence interval, 1.25-1.69]), female sex (1.30 [1.15-1.49]), previous stroke/transient ischemic attack (1.85 [1.32-2.60]), vitamin K-antagonist naive status (for vitamin K antagonist experienced, 0.85 [0.74-0.97]), moderate and severe renal impairment (1.54 [1.30-1.81] and 2.22 [1.85-2.66], respectively, compared with normal renal function), previous aspirin use (1.19 [1.04-1.37]), Asian race (1.70 [1.42-2.03]), and a CHADS2 score of >/=3 (1.64 [1.18-2.27]). CONCLUSIONS: Stroke rates are higher on OACs with some patient clinical characteristics, that is, older age, female sex, previous stroke/transient ischemic attack, vitamin K-antagonist naive status, renal impairment, previous aspirin use, and higher CHADS2 score. The identified risk factors for stroke while on an OAC could potentially be used to consider a risk assessment tool to flag up high-risk patients while on an OAC (in this case, warfarin). Whether these risk factors apply to novel OACs is uncertain.

Albrecht, E., K. R. Kirkham, et al. (2013). "Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis." Anaesthesia 68(1): 79-90.

Intravenous magnesium has been reported to improve postoperative pain; however, the evidence is inconsistent. The objective of this quantitative systematic review is to evaluate whether or not the peri-operative administration of intravenous magnesium can reduce postoperative pain. Twenty-five trials comparing magnesium with placebo were identified. Independent of the mode of administration (bolus or continuous infusion), peri-operative magnesium reduced cumulative intravenous morphine consumption by 24.4% (mean difference: 7.6 mg, 95% CI -9.5 to -5.8 mg; p < 0.00001) at 24 h postoperatively. Numeric pain scores at rest and on movement at 24 h postoperatively were reduced by 4.2 (95% CI -6.3 to -2.1; p < 0.0001) and 9.2 (95% CI -16.1 to -2.3; p = 0.009) out of 100, respectively. We conclude that peri-operative intravenous magnesium reduces opioid consumption, and to a lesser extent, pain scores, in the first 24 h postoperatively, without any reported serious adverse effects.

Albuquerque, L. E., L. O. Tso, et al. (2013). "Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles." Cochrane Database Syst Rev 1: CD002808.

BACKGROUND: Gonadotrophin-releasing hormone agonist (GnRHa) is commonly used to switch off (down regulate) the pituitary gland and thus suppress ovarian activity in women undergoing in vitro fertilisation (IVF). Other fertility drugs (gonadotrophins) are then used to stimulate ovulation in a controlled manner. Among the various types of pituitary down regulation protocols in use, the long protocol achieves the best clinical pregnancy rate. The long protocol requires GnRHa administration until suppression of ovarian activity occurs, within approximately 14 days. GnRHa can be used either as daily low-dose injections or through a single injection containing higher doses of the drug (depot). It is unclear which of these two forms of administration is best, and whether single depot administration may require higher doses of gonadotrophins. OBJECTIVES: To compare the effectiveness and safety of a single depot dose of GHRHa versus daily GnRHa doses in women undergoing IVF. SEARCH METHODS: We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to July 2012), EMBASE (1980 to July 2012) and LILACS (1982 to July 2012). We also screened the reference lists of articles. SELECTION CRITERIA: We included RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles in couples with any cause of infertility, using various methods of ovarian stimulation. The primary review outcomes were live birth or ongoing pregnancy, clinical pregnancy and ovarian hyperstimulation syndrome (OHSS). Other outcomes included number of oocytes retrieved, miscarriage, multiple pregnancy, number of gonadotrophin (FSH) units used for ovarian stimulation, duration of gonadotrophin treatment, cost and patient convenience. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed study quality. For dichotomous outcomes, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) per woman randomised. Where appropriate, we pooled studies. MAIN RESULTS: Sixteen studies were eligible for inclusion (n = 1811 participants), 12 (n = 1366 participants) of which were suitable for meta-analysis. No significant heterogeneity was detected.There were no significant differences between depot GnRHa and daily GnRHa in live birth/ongoing pregnancy rates (OR 0.95, 95% CI 0.70 to 1.31, seven studies, 873 women), but substantial differences could not be ruled out. Thus for a woman with a 24% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 18% and 29%.There was no significant difference between the groups in clinical pregnancy rate (OR 0.96, 95% CI 0.75 to 1.23, 11 studies, 1259 women). For a woman with a 30% chance of achieving clinical pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 25% and 35%.There was no significant difference between the groups in the rate of severe OHSS (OR 0.84, 95% CI 0.29 to 2.42, five studies, 570 women), but substantial differences could not be ruled out. For a woman with a 3% chance of severe OHSS using daily GnRHa injections, the corresponding risk using GnRHa depot would be between 1% and 6%.Compared to women using daily GnRHa, those on depot administration required significantly more gonadotrophin units for ovarian stimulation (standardised mean difference (SMD) 0.26, 95% CI 0.08 to 0.43, 11 studies, 1143 women) and a significantly longer duration of gonadotrophin use (mean difference (MD) 0.65, 95% CI 0.46 to 0.84, 10 studies, 1033 women).Study quality was unclear due to poor reporting. Only four studies reported live births as an outcome and only five described adequate methods for concealment of allocation. AUTHORS' CONCLUSIONS: We found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment.

Alcoba, G., M. Kerac, et al. (2013). "Do children with uncomplicated severe acute malnutrition need antibiotics? A systematic review and meta-analysis." PLoS One 8(1): e53184.

BACKGROUND: Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation. METHODS AND FINDINGS: OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27-55%) vs 22% (IQR 17-23%) and population-weighted-means 52.9% (range 23-57%) vs 35.4% (range 6.7-42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM. CONCLUSIONS: The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable monitoring, we believe that there is sufficient equipoise for placebo controlled RCTs, the only robust way to demonstrate true efficacy.

Al-Dakkak, I., S. Patel, et al. (2013). "The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: A systematic review and meta-analysis." AIDS Care 25(4): 400-14.

Abstract Poor adherence to antiretroviral therapies (ARTs) in human immunodeficiency virus (HIV)-infected patients increases the risk of incomplete viral suppression, development of viral resistance, progression to acquired immune deficiency syndrome and death. This study assesses the impact of specific treatment-related adverse events (AEs) on adherence to ART in the adult HIV patient population. A systematic review of studies involving adult HIV-infected patients aged >/= 16 years that reported an odds ratio (OR) for factors affecting adherence to ART was conducted through a search of the EMBASE(R) and Medline(R) databases. Database searches were complemented with a search of titles in the bibliographies of review papers. Studies conducted in populations limited to a particular demographic characteristic or behavioural risk were excluded. To qualify for inclusion into a meta-analysis, treatment-related AEs had to be defined similarly across studies. Also, multiple ORs from the same study were included where study sub-groups were distinct. Random effects models were used to pool ORs. In total, 19 studies and 18 ART-related AEs were included in meta-analyses. Adherence to ART was significantly lower in patients with non-specific AEs than in patients who did not experience AEs [OR = 0.623; 95% confidence interval (CI): 0.465-0.834]. Patients with specific AEs such as fatigue (OR = 0.631; 95% CI: 0.433-0.918), confusion (OR = 0.349; 95% CI: 0.184-0.661), taste disturbances (OR = 0.485; 95% CI: 0.303-0.775) and nausea (OR = 0.574; 95% CI: 0.427-0.772) were significantly less likely to adhere to ART compared to patients without these AEs. Knowledge of specific treatment-related AEs may allow for targeted management of these events and a careful consideration of well-tolerated treatment regimens to improve ART adherence and clinical outcomes.

Alfred, T., Y. Ben-Shlomo, et al. (2013). "Genetic markers of bone and joint health and physical capability in older adults: the HALCyon programme." Bone 52(1): 278-85.

BACKGROUND: Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability. METHODS: As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90+ years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance. RESULTS: Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p=0.05, n=11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures. CONCLUSION: Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.

Alfred, T., Y. Ben-Shlomo, et al. (2013). "Genetic Variants Influencing Biomarkers of Nutrition Are Not Associated with Cognitive Capability in Middle-Aged and Older Adults." J Nutr.

Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and beta-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled beta on z-score for carriers vs. noncarriers: -0.05 (95% CI: -0.09, -0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D-raising allele of rs2282679 [pooled beta per T allele: -0.03 (95% CI: -0.05, -0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.

Alhazzani, W., F. Alenezi, et al. (2013). "Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis*." Crit Care Med 41(3): 693-705.

BACKGROUND: : Critically ill patients may develop bleeding caused by stress ulceration. Acid suppression is commonly prescribed for patients at risk of stress ulcer bleeding. Whether proton pump inhibitors are more effective than histamine 2 receptor antagonists is unclear. OBJECTIVES: : To determine the efficacy and safety of proton pump inhibitors vs. histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in the ICU. SEARCH METHODS: : We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles. SELECTION CRITERIA: Randomized controlled parallel group trials comparing proton pump inhibitors to histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in critically ill patients, published before March 2012. DATA COLLECTION AND ANALYSIS: : Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were clinically important upper gastrointestinal bleeding and overt upper gastrointestinal bleeding; secondary outcomes were nosocomial pneumonia, ICU mortality, ICU length of stay, and Clostridium difficile infection. Trial authors were contacted for additional or clarifying information. RESULTS: : Fourteen trials enrolling a total of 1,720 patients were included. Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19-0.68; p = 0.002; I = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21-0.59; p < 0.0001; I = 15%). There were no differences between proton pump inhibitors and histamine 2 receptor antagonists in the risk of nosocomial pneumonia (relative risk 1.06; 95% confidence interval 0.73-1.52; p = 0.76; I = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83-1.24; p = 0.91; I = 0%), or ICU length of stay (mean difference -0.54 days; 95% confidence interval -2.20 to 1.13; p = 0.53; I = 39%). No trials reported on C. difficile infection. CONCLUSIONS: : In critically ill patients, proton pump inhibitors seem to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding. The robustness of this conclusion is limited by the trial methodology, differences between lower and higher quality trials, sparse data, and possible publication bias. We observed no differences between drugs in the risk of pneumonia, death, or ICU length of stay.

Alhazzani, W., O. Smith, et al. (2013). "Toothbrushing for critically ill mechanically ventilated patients: a systematic review and meta-analysis of randomized trials evaluating ventilator-associated pneumonia." Crit Care Med 41(2): 646-55.

BACKGROUND: Oral care may decrease ventilator-associated pneumonia in the ICU. The objective of this review was to summarize and critically appraise randomized trials in mechanically ventilated patients in the ICU testing the effect of oral care strategies involving toothbrushing on ventilator-associated pneumonia. SEARCH METHODS: We searched EMBASE, MEDLINE, and the Cochrane Controlled Trials Register and Database of Systematic Reviews from 1980 until March 2012, independently and in duplicate, as well as personal files and reference lists. In duplicate, articles were selected if they were randomized trials, enrolled adult critically ill patients, compared any kind of oral care involving toothbrushing with any other kind of oral care or control with or without toothbrushing, and examined ventilator-associated pneumonia. In duplicate, we abstracted trial characteristics and quality using the Cochrane risk of bias tool. The results were combined using a random effects model. RESULTS: We included six trials enrolling 1,408 patients, five of which compared toothbrushing to usual oral care and one of which compared electric with manual toothbrushing. In four trials, there was a trend toward lower ventilator-associated pneumonia rates (risk ratio, 0.77; 95% confidence interval, 0.50-1.21; p = 0.26). This trend was also observed in one trial reporting fewer cases of ventilator-associated pneumonia per 1,000 ventilator days (20.68 vs. 25.89; p = 0.53) in patients receiving toothbrushing vs. no toothbrushing. The only trial with low risk of bias suggested that toothbrushing significantly reduced ventilator-associated pneumonia (risk ratio, 0.26; 95% confidence interval, 0.10-0.67; p = 0.006). Use of chlorhexidine antisepsis seems to attenuate the effect of toothbrushing on ventilator-associated pneumonia (p for the interaction = 0.02). One trial comparing electric vs. manual toothbrushing showed no difference in ventilator-associated pneumonia rates (risk ratio, 0.96; 95% confidence interval, 0.47-1.96; p = 0.91). Toothbrushing did not impact on length of ICU stay, or ICU or hospital mortality. CONCLUSIONS: In intubated, mechanically ventilated critically ill patients, toothbrushing did not significantly reduce the risk of ventilator-associated pneumonia overall. Toothbrushing has no effect on mortality or length of stay. Electric and manual toothbrushing seem to have similar effects. More research is needed on this aspect of oral care to evaluate its potential to decrease ventilator-associated pneumonia.

Ali, S., S. Mealing, et al. (2013). "The use of individual patient-level data (IPD) to quantify the impact of pretreatment predictors of response to treatment in chronic hepatitis B patients." BMJ Open 3(1).

OBJECTIVES: Evidence synthesis is an integral part decision-making by reimbursement agencies. When direct evidence is not available, network-meta-analysis (NMA) techniques are commonly used. This approach assumes that the trials are sufficiently similar in terms of treatment-effect modifiers. When imbalances in potential treatment-effect modifiers exist, the NMA approach may not produce fair comparisons. The objective of this study was to identify and quantify the interaction between treatment-effect and potential treatment-effect modifiers, including time-of-response measurement and baseline viral load in chronic hepatitis B (CHB) patients. DESIGN: Retrospective patient-level data econometric analysis. PARTICIPANTS: 1353 individuals from two randomised controlled trials of nucleoside-naive CHB taking 0.5 mg entecavir (n=679) or 100 mg lamivudine (n=668) daily for 48 weeks. INTERVENTIONS: Hepatitis B virus (HBV) DNA levels for both drugs were measured at baseline and weeks 24, 36 and 48. Generalised estimating equation for repeated binary responses was used to identify treatment-effect modifiers for response defined at </=400 or </=300 copies/ml. PRIMARY OUTCOME MEASURES: OR at 48 weeks. RESULTS: The OR for the time-of-response measurement and treatment-effect interaction term was 1.039 (p=0.00) and 1.035 (p=0.00) when response was defined at </=400 or </=300 copies/ml, respectively. The baseline HBV DNA and treatment-effect interaction OR was 0.94 (p=0.047) and 0.95 (p=0.096), respectively, for the two response definitions suggesting evidence of interaction between baseline disease activity and treatment effect. The interaction between HBeAg status and treatment effect was not statistically significant. CONCLUSIONS: The measurement time point seems to modify the relative treatment effect of entacavir compared to lamivudine, measured on the OR scale. Evidence also suggested that differences in baseline viral load may also alter relative treatment effect. Meta-analyses should account for such modifiers when generating relative efficacy estimates.

Alijotas-Reig, J. (2013). "Treatment of refractory obstetric antiphospholipid syndrome: the state of the art and new trends in the therapeutic management." Lupus 22(1): 6-17.

OBJECTIVE: To date, there are no reliable data regarding the actual treatment received by women with refractory obstetric antiphospholipid syndrome (OAPS). The aim of this study was to assess current clinical evidence and new trends in the treatment of refractory OAPS. METHODS: A non-systematic but comprehensive literature search using relevant keywords was made to identify relevant articles published in English from different computerized databases: PubMed (Medline), Google Scholar electronic database search and The Cochrane Library, from January 2000 to March 2012. Studies on the treatment of poor obstetric outcomes in women with OAPS were included. Prospective randomized clinical trials, cohort studies, reviews, systematic reviews and meta-analysis were retrieved. RESULTS: A total of 130 articles were finally selected for this review, including 17 randomized clinical trials and four meta-analyses. The majority of articles were non-randomized original papers and basic and clinical reviews. CONCLUSION: Up to 20% of women with OAPS do not receive the currently recommended therapeutic regimen. Unfortunately, well-designed studies regarding the usefulness of new drugs in refractory OAPS are scarce. Hydroxychloroquine and low-dose prednisolone appear to be useful when added to standard therapy. Current data do not support the use of intravenous immunoglobulins in this field. The role played by double anti-aggregant therapy, fondaparinux, vitamin D, pentoxifylline and TNF-targeted therapies should be tested in well-designed studies.

Aljasir, B., J. P. Ioannidis, et al. (2013). "Assessment of systematic effects of methodological characteristics on candidate genetic associations." Hum Genet 132(2): 167-78.

Candidate genetic association studies have been found to have a low replication rate in the past. Here, we aimed to assess whether aspects of reported methodological characteristics in genetic association studies may be related to the magnitude of effects observed. An observational, literature-based investigation of 511 case-control studies of genetic association studies indexed in 2007, was undertaken. Meta-regression analyses were used to assess the relationship between 23 reported methodological characteristics and the magnitude of genetic associations. The 511 studies had been conducted in 52 countries and were published in 220 journals (median impact factor 5.1). The multivariate meta-regression model of methodological characteristics plus disease category accounted for 17.2 % of the between-study variance in the magnitude of the reported genetic associations. Our findings are consistent with the view that better conducted and better reported genetic association research may lead to less inflated results.

Aljumah, A. A. and M. H. Murad (2013). "Pegylated versus standard interferon plus ribavirin in chronic hepatitis C genotype 4: A systematic review and meta-analysis." Hepatol Res.

AIM: Treatment of hepatitis C genotype 4 (HCV-G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta-analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR). METHODS: We searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta-analysis was used to pool the risk ratio (RR) of achieving SVR across trials. RESULTS: Five RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR = 1.51, 95% confidence interval [CI] = 1.08-2.10). SVR was significantly higher in PEG IFN-alpha-2a compared to the -alpha-2b group (P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR (P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity. CONCLUSION: In treatment-naive patients with HCV-G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.

Alkharfy, T. M. (2013). "Induced hypothermia to treat neonatal hypoxic-ischemic encephalopathy. Review of literature with meta-analysis and development of national protocol." Neurosciences (Riyadh) 18(1): 18-26.

The efficacy of induced hypothermia to treat hypoxic-ischemic encephalopathy (HIE) in term infants has been evaluated in 6 multicenter randomized controlled trials. Meta-analysis of these trials shows that hypothermia in the first 6 hours after moderately severe HIE reduced the risk rate of death or neurological impairment at 18 months of age; risk ratio (RR): 0.81 (95% confidence interval [CI]: 0.71 to 0.93, p=0.002); risk difference -0.11 (95% CI: -0.18 to -0.04), with a number needed to treat of 9 (95% CI: 5-25). It also showed that treatment with hypothermia was associated with an increased rate of intact survival; RR: 1.53 (95% CI: 1.22-1.93, p<0.001); risk difference: 0.12 (95% CI: 0.06-0.18), with a number need to treat of 8 (95% CI: 5-17). We developed a national protocol using a simplified method of cooling. This protocol will hopefully lead to a widespread implementation of induced hypothermia in different settings within Saudi Arabia.

Alldred, D. P., D. K. Raynor, et al. (2013). "Interventions to optimise prescribing for older people in care homes." Cochrane Database Syst Rev 2: CD009095.

BACKGROUND: There is a substantial body of evidence that prescribing for care home residents is suboptimal and requires improvement. Consequently, there is a need to identify effective interventions to optimise prescribing and resident outcomes in this context. OBJECTIVES: The objective of the review was to determine the effect of interventions to optimise prescribing for older people living in care homes. SEARCH METHODS: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library (Issue 11, 2012); Cochrane Database of Systematic Reviews, The Cochrane Library (Issue 11, 2012); MEDLINE OvidSP (1980 on); EMBASE, OvidSP (1980 on); Ageline, EBSCO (1966 on); CINAHL, EBSCO (1980 on); International Pharmaceutical Abstracts, OvidSP (1980 on); PsycINFO, OvidSP (1980 on); conference proceedings in Web of Science, Conference Proceedings Citation Index - SSH & Science, ISI Web of Knowledge (1990 on); grey literature sources and trial registries; and contacted authors of relevant studies. We also reviewed the references lists of included studies and related reviews (search period November 2012). SELECTION CRITERIA: We included randomised controlled trials evaluating interventions aimed at optimising prescribing for older people (aged 65 years or older) living in institutionalised care facilities. Studies were included if they measured one or more of the following primary outcomes, adverse drug events; hospital admissions;mortality; or secondary outcomes, quality of life (using validated instrument); medication-related problems; medication appropriateness (using validated instrument); medicine costs. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. A narrative summary of results was presented. MAIN RESULTS: The eight included studies involved 7653 residents in 262 (range 1 to 85) care homes in six countries. Six studies were cluster-randomised controlled trials and two studies were patient-randomised controlled trials. The interventions evaluated were diverse and often multifaceted. Medication review was a component of seven studies, three studies involved multidisciplinary case-conferencing, two studies involved an educational element for care home staff and one study evaluated the use of clinical decision support technology. Due to heterogeneity, results were not combined in a meta-analysis. There was no evidence of an effect of the interventions on any of the primary outcomes of the review (adverse drug events, hospital admissions and mortality). No studies measured quality of life. There was evidence that the interventions led to the identification and resolution of medication-related problems. There was evidence from two studies that medication appropriateness was improved. The evidence for an effect on medicine costs was equivocal. AUTHORS' CONCLUSIONS: Robust conclusions could not be drawn from the evidence due to variability in design, interventions, outcomes and results. The interventions implemented in the studies in this review led to the identification and resolution of medication-related problems, however evidence of an effect on resident-related outcomes was not found. There is a need for high-quality cluster-randomised controlled trials testing clinical decision support systems and multidisciplinary interventions that measure well-defined, important resident-related outcomes.

Allebrandt, K. V., N. Amin, et al. (2013). "A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila." Mol Psychiatry 18(1): 122-32.

Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 x 10(-8)) in the ABCC9 gene that explains approximately 5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.

Allen-Petersen, B. L., C. J. Carter, et al. (2013). "Protein kinase Cdelta is required for ErbB2-driven mammary gland tumorigenesis and negatively correlates with prognosis in human breast cancer." Oncogene.

Protein kinase C delta (PKCdelta) regulates apoptosis in the mammary gland, however, the functional contribution of PKCdelta to the development or progression of breast cancer has yet to be determined. Meta-analysis of ErbB2-positive breast cancers shows increased PKCdelta expression, and a negative correlation between PKCdelta expression and prognosis. Here, we present in-vivo evidence that PKCdelta is essential for the development of mammary gland tumors in a ErbB2-overexpressing transgenic mouse model, and in-vitro evidence that PKCdelta is required for proliferative signaling downstream of the ErbB2 receptor. Mouse mammary tumor virus (MMTV)-ErbB2 mice lacking PKCdelta (deltaKO) have increased tumor latency compared with MMTV-ErbB2 wild-type (deltaWT) mice, and the tumors show a dramatic decrease in Ki-67 staining. To explore the relationship between PKCdelta and ErbB2-driven proliferation more directly, we used MCF-10A cells engineered to express a synthetic ligand-inducible form of the ErbB2 receptor. Depletion of PKCdelta with short hairpin RNA inhibited ligand-induced growth in both two-dimensional (2D) (plastic) and three-dimensional (3D) (Matrigel) culture, and correlated with decreased phosphorylation of the ErbB2 receptor and reduced activation of Src and MAPK/ERK pathways. Similarly, in human breast cancer cell lines in which ErbB2 is overexpressed, depletion of PKCdelta suppresses proliferation, Src and ERK activation. PKCdelta appears to drive proliferation through the formation of an active ErbB2/PKCdelta/Src signaling complex, as depletion of PKCdelta disrupts association of Src with the ErbB2 receptor. Taken together, our studies present the first evidence that PKCdelta is a critical regulator of ErbB2-mediated tumorigenesis, and suggest further investigation of PKCdelta as a target in ErbB2-positive breast cancer.Oncogene advance online publication, 11 March 2013; doi:10.1038/onc.2013.59.

Almadi, M. A., A. N. Barkun, et al. (2013). "No benefit of covered vs uncovered self-expandable metal stents in patients with malignant distal biliary obstruction: a meta-analysis." Clin Gastroenterol Hepatol 11(1): 27-37 e1.

BACKGROUND & AIMS: Self-expandable metal stents (SEMS) are used in patients with malignant distal biliary obstruction; trials that compared covered and uncovered SEMS reported different results because of heterogeneous designs and patient populations. These studies compared patency of uncovered SEMS and covered SEMS, along with rates of pancreatitis, cholecystitis, cholangitis, SEMS migration, bleeding, perforation, and recurrent biliary obstruction. METHODS: We performed a meta-analysis to compare the effects of covered and uncovered SEMS in patients with malignant distal biliary obstruction. We identified randomized controlled trials by using a literature search from 1980 through March 2012. We evaluated data from 5 full articles and 4 abstracts, comprising 1061 patients, and assessed statistical heterogeneity and publication bias. RESULTS: The weighted mean difference in the stent patency duration could only be calculated on the basis of 2 studies, but it was 67.9 days longer for covered SEMS than for uncovered SEMS (95% confidence interval [CI], 60.3-75.5). A summary analysis of data from 4 trials demonstrated no differences in patency of covered vs uncovered SEMS after 6 months (odds ratio [OR], 1.82; 95% CI, 0.62-5.25) or 12 months (OR, 1.25; 95% CI, 0.65-2.39). There were also no differences in the rates of pancreatitis, cholecystitis, perforation, bleeding, or cholangitis; length of hospital stay; or number of recurrent biliary obstructions. However, covered SEMS had a higher migration rate (OR, 7.13; 95% CI, 2.29-22.21). Patients with covered SEMS had a lower rate of tumor ingrowth (OR, 0.19; 95% CI, 0.07-0.55) but a higher rate of tumor overgrowth (OR, 1.88; 95% CI, 1.02-3.45). No summary calculations could be completed to confidently assess patient survival. CONCLUSIONS: The use of covered SEMS, compared with uncovered SEMS, in patients with distal malignant biliary obstruction is of unclear benefit; covered SEMS have a higher rate of migration and do not appear to have longer patency.

Al-Mandeel, H., M. Y. Alhindi, et al. (2013). "Effects of intentional delivery on maternal and neonatal outcomes in pregnancies with preterm prelabour rupture of membranes between 28 and 34 weeks of gestation: a systematic review and meta-analysis." J Matern Fetal Neonatal Med 26(1): 83-9.

OBJECTIVE: To assess the effects of intentional delivery (ID) over expectant management (EM) in pregnancies complicated by preterm prelabour rupture of membranes (PPROM) between 28 and 34 weeks of gestation on maternal and neonatal outcomes. METHODS: We searched Ovid MEDLINE, EMBASE, CINAHL, CENTRAL and Science Citation Index; contacted experts and checked reference lists of relevant studies. Studies were included if they were randomized controlled trials in all languages. RESULTS: Five randomized trials were included and 488 subjects were analyzed. Overall, the results showed significant heterogeneity. Maternal infection as well as respiratory distress syndrome (RDS) & neonatal sepsis (NS) were not different between the two groups. Neonatal death, however, was significantly higher (risk ratio: 5.81; 95% CI: 1.35-25.08; p = 0.03) in the ID group after excluding studies that gave antenatal steroids. Incidence of cesarean section was significantly higher in the intentional delivery group, as well (risk ratio: 1.35; 95% CI: 1.02-1.80; p = 0.03). CONCLUSION: Based on the available evidence, ID in pregnancies complicated with PPROM between 28 and 34 weeks carries some maternal and neonatal risks with no added benefits. Thus, this treatment should not be considered as an option for women with PPROM before 34 weeks of gestation in the absence of other indications for early delivery.

Almeamar, H. A., V. Ramachandran, et al. (2013). "Analysis of partial AZFc deletions in Malaysian infertile male subjects." Syst Biol Reprod Med 59(2): 99-107.

Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions.

Almekhlafi, M. A., B. K. Menon, et al. (2013). "A meta-analysis of observational intra-arterial stroke therapy studies using the Merci device, Penumbra system, and retrievable stents." AJNR Am J Neuroradiol 34(1): 140-5.

BACKGROUND AND PURPOSE: The time from arterial puncture to successful recanalization is an important milestone toward timely recanalization. With the significant improvement in recanalization rates by using thrombectomy devices, procedural time to recanalization is becoming a determinant factor in choosing among available devices. We aimed to assess the impact of time to recanalization on the outcome of intra-arterial stroke therapies. MATERIALS AND METHODS: We conducted a meta-analysis of studies reporting procedural times in patients with stroke treated with the MD, PS, and RS. RESULTS: We identified 16 eligible studies: 4 on the MD (n = 357), 8 on the PS (n = 455), and 4 on RS (n = 113). Merci device studies described total procedural duration, while PS and RS studies described puncture-to-recanalization times. With a random-effects model, mean procedural duration for the MD was 120 minutes (95% CI, 105.7-134.2 minutes). Mean puncture to recanalization time for the PS was 64.6 minutes (95% CI, 44.4-84.8 minutes) and 54.7 minutes for RS (95% CI, 47.3-62.2 minutes). Successful recanalization was achieved in 211 of 357 patients (59.1%) in the MD studies (95% CI, 49.3-77.7), 394 of 455 (86.6%) in the PS studies (95% CI, 84.1-93.8), and 105 of 113 (92.9%) in the RS studies (95% CI, 90.9-99.9). Functional independence (mRS </=2) was achieved in 31.5% of patients in the MD studies, 36.6% in the PS studies, and 46.9% in the RS studies. CONCLUSIONS: The use of the PS and RS was associated with comparable procedural time to recanalization. Available data did not allow this parameter to be determined for trials using the MD. Retrievable stents achieved the highest rate of successful recanalization and functional outcome and the lowest mortality.

Almenawer, S. A., I. Bogza, et al. (2013). "The value of scheduled repeat cranial computed tomography after mild head injury: single-center series and meta-analysis." Neurosurgery 72(1): 56-62; discussion 63-4.

BACKGROUND: After an initial computed tomography (CT) scan revealing intracranial hemorrhage resulting from traumatic brain injury, a standard of care in many trauma centers is to schedule a repeat CT scan to rule out possible progression of bleed. OBJECTIVE: To evaluate the utility of routine follow-up CT in changing the management of mild head injury patients despite clinical stability, although repeat imaging is indicated to assess a deteriorating patient. METHODS: The trauma database at our institution was retrospectively reviewed and the literature was searched to identify patients after mild head injury with positive initial CT finding and scheduled repeat scan. Patients were divided into 2 groups for comparison. Group A included patients who had intervention based on neurological examination changes. Group B comprised patients requiring a change in management according to CT results exclusively. The meta-analysis of the present cohort and included articles was performed with a random-effects model. RESULTS: Overall, 15 studies and 445 patients met our eligibility criteria, totaling 2693 patients. Intervention rates of groups A and B were 2.7% (95% confidence interval, 1.7-3.9; P = .003) and 0.6% (95% confidence interval, 0.3-1; P = .21), respectively. The statistical difference between both intervention rates was clinically significant with P < .001. CONCLUSION: The available evidence indicates that it is unnecessary to schedule a repeat CT scan after mild head injury when patients are unchanged or improving neurologically. In the absence of supporting data, we question the value of routine follow-up imaging given the associated accumulative increase in cost and risks.

Al-Momani, H. and B. M. Stephenson (2013). "Comparison of mesh-plug and Lichtenstein for inguinal hernia repair: a meta-analysis of randomized controlled trials. Li J, Ji Z, Li Y. Hernia 2012 Jul 28. doi: 10.1007/s10029-012-0974-6." Hernia 17(1): 151.

Al-Rubeaan, K., K. Siddiqui, et al. (2013). "ACE I/D and MTHFR C677T polymorphism are significantly associated with type 2 diabetes in Arab ethnicity: A Meta- analysis." Gene.

In this meta-analysis study, SNPs were investigated for their association with Type 2 Diabetes (T2D) in both Arab and Caucasian ethnicities. A total of 55 SNPs were analyzed, of which 11 fulfilled the selection criteria, and were used for analysis. It was found that TCF7L2 rs7903146 was significantly associated with a pooled OR of 1.155 (95%C.I.=1.059-1.259), p<0.0001 and I2=78.30% among the Arab population, whereas among Caucasians, the pooled OR was 1.45 (95%C.I.=1.386-1.516) , p<0.0001 and I2=77.20%. KCNJ11 rs5219 was significantly associated in both the populations with a pooled OR of 1.176(1.092-1.268), p<0.0001 and I2=32.40% in Caucasians and a pooled OR of 1.28(1.111-1.475), p=0.001 among Arabs. The ACE I/D polymorphism was found to be significantly associated with a pooled OR of 1.992 (95%C.I.=1.774-2.236), p<0.0001and I2=83.20% among Arab population, whereas among Caucasians, the pooled OR was 1.078 (95%C.I.=0.993-1.17), p=0.073 and I2=0%. Similarly, MTHFR C677T polymorphism was also found to be significantly associated among Arabs with a pooled OR of 1.924 (95%C.I.=1.606-2.304), p<0.0001 and I2=27.20%, whereas among Caucasians, the pooled OR was 0.986 (95%C.I.=0.868-1.122), p=0.835 and I2=0%. Meanwhile PPARG-2 Pro12Ala, CDKN2A/2B rs10811661, IGF2BP2 rs4402960, HHEX rs7923837, CDKAL1 rs7754840, EXT2 rs1113132 and SLC30A8 rs13266634 were found to have no significant association with T2D among Arabs. In conclusion, it seems from this study that both Arabs and Caucasians have different SNPs associated with T2D. Moreover; this study sheds light on the profound necessity for further investigations addressing the question of the genetic components of T2D in Arabs.

Alshaikh, B., K. Yusuf, et al. (2013). "Neurodevelopmental outcomes of very low birth weight infants with neonatal sepsis: systematic review and meta-analysis." J Perinatol.

OBJECTIVE:To study the impact of neonatal sepsis on the long-term neurodevelopmental outcome in very low birth weight (VLBW) infants.STUDY DESIGN:Systematic review and meta-analysis of observational studies comparing neurodevelopmental outcomes in VLBW infants exposed to culture-proven sepsis in the neonatal period with similar infants without sepsis.RESULT:Seventeen studies involving 15 331 infants were included in the meta-analysis. Sepsis in VLBW infants was associated with an increased risk of one or more long-term neurodevelopmental impairments (odds ratio (OR) 2.09; 95% confidence interval (CI) 1.65 to 2.65) including cerebral palsy (CP; OR 2.09; 95% CI 1.78 to 2.45). Heterogeneity (I(2)=36.9%; P=0.06) between the studies was significant and related to variations in patient characteristics, causative pathogens and follow-up methods. Sensitivity analyses based on study design, follow-up rate and year of birth were not significantly different from the overall analysis.CONCLUSION:The meta-analysis suggests that sepsis in VLBW infants is associated with a worse neurodevelopmental outcome including higher incidence of CP.Journal of Perinatology advance online publication, 17 January 2013; doi:10.1038/jp.2012.167.

Alul, F. Y., O. A. Shchelochkov, et al. (2013). "Genetic associations with neonatal thyroid-stimulating hormone levels." Pediatr Res.

Background:Elevations or deficits in thyroid hormone levels are responsible for a wide range of neonatal and adult phenotypes. Several genome-wide, candidate gene, and meta-analysis studies have examined thyroid hormones in adults; however, to our knowledge, no genetic association studies have been performed with neonatal thyroid levels.Methods:A population of Iowa neonates, term (n = 827) and preterm (n = 815), were genotyped for 45 single-nucleotide polymorphisms (SNPs). Thyroid-stimulating hormone (TSH) values were obtained from the Iowa Neonatal Metabolic Screening Program. ANOVA was performed to identify genetic associations with TSH concentrations.Results:The strongest association was rs4704397 in the PDE8B gene (P = 1.3 x 10-4), followed by rs965513 (P = 6.4 x 10-4) on chromosome 9 upstream of the FOXE1 gene. Both of these SNPs met statistical significance after correction for multiple testing. Six other SNPs were marginally significant (P < 0.05).Conclusion:We demonstrated for the first time two genetic associations with neonatal TSH levels that replicate findings with adult TSH levels. These SNPs should be considered early predictors of risk for adult diseases and conditions associated with thyroid hormone levels. Furthermore, this study provides a better understanding of the thyroid profile and potential risk for thyroid disorders in newborns.Pediatric Research (2013); doi:10.1038/pr.2013.18.

Alvarez, Y., C. Perez-Mana, et al. (2013). "Antipsychotic drugs in cocaine dependence: A systematic review and meta-analysis." J Subst Abuse Treat.

A systematic review and meta-analysis to evaluate the efficacy of antipsychotic drugs in subjects with cocaine dependence is presented. Twelve randomized, double-blind, placebo-controlled clinical trials involving 681 patients were included. Five outcome measures were evaluated: number of dropouts, cocaine use assessed by means of urine benzoylecgonine tests, self-reported cocaine use, craving and Addiction Severity Index. On average, 48% of the enrolled participants were lost to follow-up. In comparison to placebo, antipsychotics did not significantly reduce cocaine use (WMD=0.01, 95%CI=-0.12 to 0.13) or improve retention in treatment (RR 0.91, 95%CI=0.82-1.02). Risperidone reduced slightly dropouts in comparison to placebo (RR=0.87; 95%CI=0.79-0.97). To date there is insufficient evidence to justify the use of antipsychotic drugs for cocaine dependence.

Alviar, C. L., S. Devarapally, et al. (2013). "Efficacy and safety of dual calcium channel blockade for the treatment of hypertension: a meta-analysis." Am J Hypertens 26(2): 287-97.

BACKGROUND Dual calcium-channel blocker (CCB) with a dihydropyridine (DHP) and a nondihydropyridine (NDHP) has been proposed for hypertension treatment. However, the safety and efficacy of this approach is not well known. METHODS A MEDLINE/EMBASE/CENTRAL search for randomized clinical trials published on this topic from 1966 to February 2012 was performed. Efficacy outcomes of decrease in systolic (SBP) and diastolic (DBP) blood pressures from baseline, changes in heart rate (HR), and adverse effects were compared between dual CCB therapy vs. DHP or NDHP. SBP, DBP, and HR were expressed as weighted mean deviation (WMD). RESULTS A total of 6 studies with 153 patients were included. Dual CCB produced a significantly greater reduction in SBP (21.6+/-9.2 mmHg) from baseline than DHP (10.3+/-6.3 mmHg (WMD = 10.9 mmHg, P < 0.0001)) or NDHP (8.9+/-4.2 mmHg (WMD = 14.1 mmHg, P = 0.002)). Dual CCB therapy reduced DBP from baseline more than either monotherapy (dual CCB = 17.5+/-10.2 mmHg vs. DHP = 11.6+/-8.7 mmHg, WMD = 5.5 mmHg, P < 0.001; and NDHP = 10.5+/-5.6 mmHg, WMD = 5.3 mmHg, P = 0.03). Dual CCB therapy had significantly lower HR compared to DHP (P < 0.001) but was comparable to NDHP (P = 0.12) (Delta change dual CCB = -4.0+/-3.5 vs. DHP = -2.0+/-1.5 and NDHP = -6.0+/-5.0 beats/min). Dual CCB therapy did not increase adverse effects. CONCLUSIONS Dual CCB therapy lowers blood pressure significantly better than CCB monotherapy, without an increase in adverse events. However, given the lack of long-term outcome data on efficacy and safety, dual CCB therapy should be used with restraint, if at all. Large-scale long-term trials are needed to further evaluate such a strategy.

Amanzio, M., F. Benedetti, et al. (2013). "Activation likelihood estimation meta-analysis of brain correlates of placebo analgesia in human experimental pain." Hum Brain Mapp 34(3): 738-52.

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which areas consistently contribute to placebo analgesia-related networks. In the present study, we used activation likelihood estimation (ALE) meta-analysis, a state-of-the-art approach, to search for the cortical areas involved in PA in human experimental pain models. Nine fMRI studies and two PET studies investigating cerebral hemodynamic changes were included in the analysis. During expectation of analgesia, activated foci were found in the left anterior cingulate, right precentral, and lateral prefrontal cortex and in the left periaqueductal gray (PAG). During noxious stimulation, placebo-related activations were detected in the anterior cingulate and medial and lateral prefrontal cortices, in the left inferior parietal lobule and postcentral gyrus, anterior insula, thalamus, hypothalamus, PAG, and pons; deactivations were found in the left mid- and posterior cingulate cortex, superior temporal and precentral gyri, in the left anterior and right posterior insula, in the claustrum and putamen, and in the right thalamus and caudate body. Our results suggest on one hand that the modulatory cortical networks involved in PA largely overlap those involved in the regulation of emotional processes, on the other that brain nociceptive networks are downregulated in parallel with behavioral analgesia. Hum Brain Mapp, 2013. (c) 2011 Wiley Periodicals, Inc.

Amato, L., M. Davoli, et al. (2013). "Methadone at tapered doses for the management of opioid withdrawal." Cochrane Database Syst Rev 2: CD003409.

BACKGROUND: The evidence of tapered methadone's efficacy in managing opioid withdrawal has been systematically evaluated in the previous version of this review that needs to be updated OBJECTIVES: To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate. SEARCH METHODS: We searched: Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 4), PubMed (January 1966 to May 2012), EMBASE (January 1988 to May 2012), CINAHL (2003- December 2007), PsycINFO (January 1985 to December 2004), reference lists of articles. SELECTION CRITERIA: All randomised controlled trials that focused on the use of tapered methadone versus all other pharmacological detoxification treatments or placebo for the treatment of opiate withdrawal. DATA COLLECTION AND ANALYSIS: Two review authors assessed the included studies. Any doubts about how to rate the studies were resolved by discussion with a third review author. Study quality was assessed according to the criteria indicated in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: Twenty-three trials involving 2467 people were included. Comparing methadone versus any other pharmacological treatment, we observed no clinical difference between the two treatments in terms of completion of treatment, 16 studies 1381 participants, risk ratio (RR) 1.08 (95% confidence interval (CI) 0.97 to 1.21); number of participants abstinent at follow-up, three studies, 386 participants RR 0.98 (95% CI 0.70 to 1.37); degree of discomfort for withdrawal symptoms and adverse events, although it was impossible to pool data for the last two outcomes. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (eight studies), anxiolytic (two studies), paiduyangsheng (one study). Comparing methadone with placebo (two studies) more severe withdrawal and more drop-outs were found in the placebo group. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. AUTHORS' CONCLUSIONS: Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long- acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.

Amatya, B., F. Khan, et al. (2013). "Non pharmacological interventions for spasticity in multiple sclerosis." Cochrane Database Syst Rev 2: CD009974.

BACKGROUND: Spasticity is commonly experienced by people with multiple sclerosis (MS), and it contributes to overall disability in this population. A wide range of non pharmacological interventions are used in isolation or with pharmacological agents to treat spasticity in MS. Evidence for their effectiveness is yet to be determined. OBJECTIVES: To assess the effectiveness of various non pharmacological interventions for the treatment of spasticity in adults with MS. SEARCH METHODS: A literature search was performed using the Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group on using the Cochrane MS Group Trials Register which among other sources, contains CENTRAL, Medline, EMBASE, CINAHL, LILACS, PEDRO in June 2012. Manual searching in the relevant journals and screening of the reference lists of identified studies and reviews were carried out. Abstracts published in proceedings of conferences were also scrutinised. SELECTION CRITERIA: Randomised controlled trials (RCTs) that reported non pharmacological intervention/s for treatment of spasticity in adults with MS and compared them with some form of control intervention (such as sham/placebo interventions or lower level or different types of intervention, minimal intervention, waiting list controls or no treatment; interventions given in different settings), were included. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool for best-evidence synthesis. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. MAIN RESULTS: Nine RCTs (N = 341 participants, 301 included in analyses) investigated various types and intensities of non pharmacological interventions for treating spasticity in adults with MS. These interventions included: physical activity programmes (such as physiotherapy, structured exercise programme, sports climbing); transcranial magnetic stimulation (Intermittent Theta Burst Stimulation (iTBS), Repetitive Transcranial Magnetic Stimulation (rTMS)); electromagnetic therapy (pulsed electromagnetic therapy; magnetic pulsing device), Transcutaneous Electrical Nerve Stimulation (TENS); and Whole Body Vibration (WBV). All studies scored 'low' on the methodological quality assessment implying high risk of bias. There is 'low level' evidence for physical activity programmes used in isolation or in combination with other interventions (pharmacological or non pharmacological), and for repetitive magnetic stimulation (iTBS/rTMS) with or without adjuvant exercise therapy in improving spasticity in adults with MS. No evidence of benefit exists to support the use of TENS, sports climbing and vibration therapy for treating spasticity in this population. AUTHORS' CONCLUSIONS: There is 'low level' evidence for non pharmacological interventions such as physical activities given in conjunction with other interventions, and for magnetic stimulation and electromagnetic therapies for beneficial effects on spasticity outcomes in people with MS. A wide range of non pharmacological interventions are used for the treatment of spasticity in MS, but more robust trials are needed to build evidence about these interventions.

Ambrosi, P. (2013). "[Short-term clinical effects of periprocedural statin therapy]." Presse Med 42(3): 261-8.

In high-risk patients, long-term statin therapy prevents cardiovascular events. Short-term clinical benefit of statin therapy has been recently evaluated by randomized clinical trials in the setting of vascular surgery, coronary bypass surgery and percutaneous coronary interventions. According to the trial scheme, statin therapy was started either few weeks or few hours before the intervention. In the field of vascular surgery, the clinical benefit of preprocedure statin administration has been supported by DECREASE III trial. Fluvastatin significantly decreased the incidence of periprocedural myocardial ischemia as defined by ECG changes or troponin elevation. However, this study has methodological flaws, including primary endpoint modification during the trial and the lack of clinical relevance of this endpoint. The administration of statins before a coronary bypass could reduce the occurrence of postoperative atrial fibrillation, according to 4 randomized trials. This finding is discordant with the result of a recent meta-analysis of long-term published and unpublished long-term trials that showed no significant beneficial effects of statins on atrial fibrillation. Several trials have evaluated the usefulness of statin pretreatment before PCI. Most of them have found that statin pretreatment prevents periprocedural myocardial infarctions or major cardiac events. However, most of these events were isolated enzymatic elevations. Moreover, myocardial infarction definition was at odds with the recommendations in some of these trials. A recent meta-analysis of these trials has found that statin pretreatment leads to a 44% reduction in the incidence of major cardiac events at 30 days. The magnitude of this decrease is not consistent with the results of previous long-term trials evaluating statins after acute coronary syndromes. Current evidence does not strongly support short-term clinical benefit of pre-procedural statin administration.

Amin Al Olama, A., Z. Kote-Jarai, et al. (2013). "A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease." Hum Mol Genet 22(2): 408-15.

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 x 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

Amit, L., I. Ben-Aharon, et al. (2013). "The impact of Bevacizumab (Avastin) on survival in metastatic solid tumors--a meta-analysis and systematic review." PLoS One 8(1): e51780.

PURPOSE: To evaluate the effect of Bevacizumab in combination with chemotherapy on overall survival of patients with metastatic solid tumors. DESIGN: A systematic literature search to identify randomized trials comparing chemotherapy with and without Bevacizumab in metastatic cancer. The primary end point was overall survival (OS) and the secondary end points were progression free survival (PFS) and toxicity. A meta-analysis was performed for each tumor type and for the combination of all tumors. RESULTS: 24 randomized trials with 8 different types of malignancies were included in this meta-analysis. Patients treated with Bevacizumab had an OS benefit, hazard ratio (HR) 0.89 (95% CI 0.84-0.93, P<0.00001 I(2)-4%). The combined analysis showed a PFS benefit with a HR 0.71 (95% CI 0.68-0.74, P<0.00001, I(2)-54%). The toxicity analysis showed a statistically significant increase in fatal adverse events (FAEs) in the Bevacizumab treatment arm, risk ratio (RR) 1.47 (95% CI 1.1-1.98). A separate analysis of the lung cancer trials showed an increased risk of fatal pulmonary hemorrhage with a RR of 5.65 (95% CI 1.26-25.26). The risk of G3-4 adverse events was increased: RR 1.2 (95% CI 1.15-1.24). CONCLUSION: in this combined analysis Bevacizumab improved OS (with little heterogeneity) and PFS. These results should be considered in the light of lack of markers predictive of response and the increased severe and fatal toxicity seen with Bevacizumab treatment.

Amoretti, A., H. Laydner, et al. (2013). "Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis." J Am Acad Dermatol.

BACKGROUND: Androgenetic alopecia (AGA) is a genetically determined skin condition strongly age dependent and androgens are assumed to play an important role in its development. A link between AGA and prostate cancer has been hypothesized because of their similar risk factors. OBJECTIVE: We sought to systematically review the evidence available on the association between AGA and risk of prostate cancer. METHODS: We searched the electronic databases MEDLINE and Cochrane for studies examining the association between AGA and risk of prostate cancer. We estimated pooled odds ratios (OR) and 95% confidence intervals. We also analyzed the OR for individual hair loss patterns, as defined by the Hamilton scale. RESULTS: A total of 7 case-control studies including 8994 patients-4078 cases and 4916 controls-were reviewed. One cohort study was identified but did not meet our inclusion criteria. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58). LIMITATIONS: Only case-control studies, which may be subject to bias, met the inclusion criteria for this meta-analysis. CONCLUSIONS: Vertex pattern AGA was associated with a significant increased risk of prostate cancer. Any pattern AGA did not show a significant increase in the risk of prostate cancer.

Amorim, M. R. and M. A. Lima (2013). "MTRR 66A>G polymorphism as maternal risk factor for Down syndrome: a meta-analysis." Genet Test Mol Biomarkers 17(1): 69-73.

Down syndrome (DS) is the most common cause of mental retardation. Recent reports have investigated possible genetic factors that may increase maternal risk for DS. Methionine synthase reductase (5-methyltetrahydrofolate-homocysteine methyltransferase reductase MTRR) plays an important role in folic acid pathway and a common polymorphism (c.66A>G) has been associated with DS but results were controversial. This meta-analysis summarizes the available data concerning this association. Online major databases were searched to identify case-control studies regarding MTRR 66A>G polymorphism and DS. Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated for maternal risk to have a DS child both using fixed and random effects (RE) models. Eleven articles from six populations were identified, including 1226 DS mothers and 1533 control mothers. Heterogeneity among studies was significant (Q=29.7, DF=10, p=0.001; I(2)=66.3%). The pooled OR in a RE model showed an increase in the risk of having a DS child associated with the G allele (OR 1.23, 95% CI 1.02-1.49). The fixed effect pooled OR was 1.19 (95% CI 1.08-1.31). This meta-analysis indicates that maternal MTRR 66A>G polymorphism is associated with an increased risk of having a DS child.

An, X., X. Lin, et al. (2013). "Short term results of neoadjuvant chemoradiotherapy with fluoropyrimidine alone or in combination with oxaliplatin in locally advanced rectal cancer: A meta analysis." Eur J Cancer 49(4): 843-51.

BACKGROUND: Oxaliplatin (OX), in combination with fluoropyrimidine (5-fluorouracil or Capecitabine, FU)-based regimens and radiation, has been expected to both enhance primary tumour shrinkage and reduce micrometastases at distant sites in the neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, results in terms of pathologic complete response (pCR) and toxicities were inconsistent. The aim of this meta analysis was to evaluate the short term efficacy and toxicities of adding OX to FU in CRT for LARC. METHODS: We searched PubMed, EMBASE, ISI databases, Chinese Biomedical Literature Database and the Cochrane library before December, 2011. Additionally, abstracts presented at American Society of Clinical Oncology conferences held between January, 2000, and July, 2011, were searched to identify relevant clinical trials. Only randomised studies with an analysis by an intention-to-treat principle were included, and searches were restricted to those databases citing articles in English. Summary incidence rates and 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Four randomised clinical trials comparing OX/FU versus FU alone regimens in CRT for LARC met our search criteria and were assessed. A total of 3863 patients (FU, n=1937; OX/FU, n=1926) were included in the analysis. FINDINGS: The addition of OX to FU significantly improved pathologic complete response (pCR), and reduced peri-operative metastases (including intra-abdominal metastases) with an odd ratios (OR) for OX/FU compared with FU of 1.20 (95% CI, 1.01-1.42; P=0.04) and 0.51 (95% CI, 0.34-0.77; P=0.001), respectively. The grade 3/4 toxicity rate was significantly higher for OX/FU versus FU alone with an OR of 2.29 (95% CI, 1.31-4.00; P=0.004). There was no difference in the rates of positive circumferential resection margin, permanent stoma, surgical complication and death within 60d between the OX/FU and FU alone patients. The OR for the proportion of patients completing full-dose radiotherapy and completing full-dose chemotherapy were 0.32 (95% CI, 0.15-0.69; P=0.004), and 0.71 (95% CI, 0.35-1.42; P=0.33), respectively. INTERPRETATION: Adding weekly OX to FU in neoadjuvant CRT of LARC appeared to modestly increase the pCR rate and reduced the rate of intra-abdominal or peri-operative metastases in this meta analysis. Although OX/FU significantly increased grade 3/4 toxicity, it did not result in more surgical complications or postoperative deaths within 60d. The concept of combination of OX and FU in the pre-operative setting for LARC still seems promising, either with a modified schedule, or as induction therapy prior to CRT or after CRT, prior to surgery.

Anand, N., K. Sampath, et al. (2013). "Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: a Meta-Analysis." Clin Gastroenterol Hepatol.

BACKGROUND & AIMS: International guidelines for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of those with specific characteristics. We performed a meta-analysis to evaluate risk of malignancy associated with each of these features of IPMNs. METHODS: We performed a comprehensive search of MEDLINE from January 1, 1996 to November 11, 2011 for studies that included any of the features mentioned in the consensus guidelines for surgical resection of main duct and branch duct IPMNs. Data were analyzed from 41 studies for the following features: cyst size >3 cm, the presence of mural nodules, dilated main pancreatic duct, symptoms, and main duct vs branch duct IPMNs. Malignant IPMNs were defined as those with carcinoma in situ or more advanced histology. A separate meta-analysis was performed for each risk factor to calculate pooled odds ratios (ORs). A random-effects model was used, based on the assumption of variation among study populations. RESULTS: The risks of malignancy associated with individual cyst features were: cyst size >3 cm (OR, 62.4; 95% confidence interval [CI], 30.8-126.3), presence of a mural nodule (OR, 9.3; 95% CI, 5.3-16.1), dilatation of the main pancreatic duct (OR, 7.27; 95% CI, 3.0-17.4), and main vs branch duct IPMN (OR, 4.7; 95% CI, 3.3-6.9]. There was a moderate level of heterogeneity among studies (I(2) range, 34-67). CONCLUSIONS: Based on a meta-analysis, cyst features proposed by the international guidelines for resection of IPMN were highly associated with malignancy. However, based on our findings, not all cyst features should be weighted equally when considering risk of malignancy; cyst size >3 cm was most strongly associated with malignant IPMN.

Anandam, A., M. Akinnusi, et al. (2013). "Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis." Sleep Breath 17(1): 227-34.

PURPOSE: Clinical and epidemiologic investigations suggest a strong association between obesity and obstructive sleep apnea (OSA). The purpose of this study is to evaluate the currently available literature reporting on the effectiveness of dietary weight loss in treating OSA among obese patients. METHODS: Relevant studies were identified by computerized searches of PubMed, EMBASE, CINAHL, Web of Science, and The Cochrane Central Register of Controlled Trials through September 2011 as well as the reference lists of all obtained articles. Information on study design, patient characteristics, pre- and post-dietary weight loss measures of OSA and body mass index (BMI), and study quality was obtained. Data were extracted by two independent analysts. Weighted averages using a random-effects model are reported with 95 % confidence intervals. RESULTS: Nine articles representing 577 patients were selected. Dietary weight loss program resulted in a pooled mean BMI reduction of 4.8 kg/m(2) (95 % confidence interval [CI] 3.8-5.9). The random-effects pooled apnea hypopnea (AHI) indices at pre- and post-dietary intervention were 52.5 (range 10.0-91.0) and 28.3 events/h (range 5.4-64.5), respectively (p < 0.001). Compared to control, the weighted mean difference of AHI was decreased by -14.3 events/h (95 % CI -23.5 to -5.1; p = 0.002) in favor of the dietary weight loss programs. CONCLUSIONS: Dietary weight loss programs are effective in reducing the severity of OSA but not adequate in relieving all respiratory events. Weight reduction programs should be considered as adjunct rather than curative therapy.

Anastasiadis, K., P. Antonitsis, et al. (2013). "Use of minimal extracorporeal circulation improves outcome after heart surgery; a systematic review and meta-analysis of randomized controlled trials." Int J Cardiol 164(2): 158-69.

BACKGROUND: The question whether use of minimal extracorporeal circulation (MECC) influences patients' outcome remains unanswered. We performed a systemic review of the literature and a meta-analysis of randomized controlled trials to evaluate the impact of MECC compared to conventional extracorporeal circulation (CECC) on mortality and major adverse cardiovascular events in patients undergoing heart surgery. METHODS: We independently conducted a systemic review of English and non-English articles using Medline, Embase and Cochrane database. Random allocation to treatment with a minimum of 40 patients in both groups was considered mandatory for inclusion in the meta-analysis. Primary outcomes were operative mortality and major adverse cardiac and cerebrovascular events comprising death before discharge, myocardial infarction and neurologic damage. RESULTS: We included 24 studies comparing MECC vs. CECC with a total of 2770 patients. Use of MECC was associated with a significant decrease in mortality (0.5% vs. 1.7%, P=0.02), in the risk of postoperative myocardial infarction (1.0% vs. 3.8%, P=0.03) and reduced rate of neurologic events (2.3% vs. 4.0%, P=0.08). Additionally, MECC was associated with reduced systemic inflammatory response as measured by polymorphonuclear elastase, hemodilution as calculated by hematocrit drop after procedure, need for red blood cell transfusion, reduced levels of peak troponin release, incidence of low cardiac output syndrome, need for inotropic support, peak creatinine level, occurrence of postoperative atrial fibrillation, duration of mechanical ventilation and intensive care unit stay. CONCLUSIONS: Use of MECC in heart surgery resulted in improved short-term outcome as reflected by reduced mortality and morbidity compared with conventional extracorporeal circulation.

Anders, M., M. Fehlker, et al. (2013). "Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas." Mol Carcinog 52(1): 29-38.

Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray studies. Own microarray and quantitative RT-PCR data were obtained from a colorectal carcinoma cohort. Applying highly stringent inclusion criteria, 15 cancer array studies were suitable for our analysis. These studies provided 789 tumor specimens and 190 samples of healthy tissues yielding a total of approx. 1,000,000 gene expression measurements. Meta-analysis on the expression of 480 angiogenesis-related genes in 10 cancer types identified a characteristic, entity-independent "global" cancer expression signature of 25 angiogenesis-related genes showing high frequency down-regulation when compared to corresponding healthy tissues. Furthermore, we characterized 25 genes displaying frequent up-regulation, yet less often than the 25 down-regulated genes. Comparative inter-study cross-validation revealed that both signatures discriminate cancers from healthy tissues with high accuracy in independent test sets. Moreover, own microarray data of colorectal carcinomas confirmed the specific and sensitive discriminating potential of both signatures. These results were validated by quantitative RT-PCR for eight genes displaying the highest differences in the microarray analysis. Our study for the first time defines global gene expression signatures linked to angiogenesis in carcinomas. Our findings suggest that gene down-regulation may represent a central aspect of tumor angiogenesis.

Andersen, G., L. T. Dalgaard, et al. (2013). "The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17 636 Danes." Int J Obes (Lond) 37(2): 175-81.

CONTEXT: Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in beta-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus. OBJECTIVE: To determine the influence of a functional UCP2 promoter polymorphism (-866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes. DESIGN: We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations. RESULTS: We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05). CONCLUSIONS: The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.

Andersen, L. V., G. Y. Lip, et al. (2013). "Upper limb arterial thromboembolism: A systematic review on incidence, risk factors, and prognosis including a meta-analysis of risk-modifying drugs." J Thromb Haemost.

OBJECTIVES: The aim of this review is to focus on risk factors, risk-modifying drugs, prognosis, and relationship between atrial fibrillation (AF) and arterial thromboembolism of the upper limb. METHODS: We searched MEDLINE for studies on the epidemiology of upper limb thromboembolism from 1965 to June 2012. We also searched for contemporary, phase III randomized trial data on systemic (non-stroke) thromboembolism comparing warfarin to new oral anticoagulants (NOAC) in patients with atrial fibrillation published after the year 1999. RESULTS: The incidence of upper limb thromboembolectomy was 3.3 among men and 5.2 among women per 100,000 person-years; risk of limb amputation, stroke and death after thromboembolectomy was increased. There was an increased risk of thromboembolectomy of the upper limb in patients with AF diagnosed with hypertension (Hazard ratio (HR) 2.2-2.9), myocardial infarction (HR 2.9-3.9), heart failure (HR 1.6-1.9) and stroke (HR 2.2-3.8). For those diagnosed with diabetes mellitus, the risk was non-significantly increased by 1.2 to 1.4. Females had 1.8-fold (95% CI, 1.5-2.3) fold increased risk of thromboembolectomy compared to men. The risk reduction of systemic embolism with NOAC compared to warfarin in patients with AF is similar to that seen with warfarin (odds ratio 0.79 (95% CI 0.38, 1.64)). CONCLUSIONS: Age, female sex, AF, hypertension, diabetes, myocardial infarction, heart failure and stroke are most common risk factors for thromboembolectomy of the upper limb. The availability of NOAC holds promise in reducing the risk of systemic thromboembolism, but specific data are still limited. (c) 2013 International Society on Thrombosis and Haemostasis.

Andersen, V., R. Holst, et al. (2013). "Systematic review: diet-gene interactions and the risk of colorectal cancer." Aliment Pharmacol Ther 37(4): 383-91.

BACKGROUND: Diet contributes significantly to colorectal cancer (CRC) aetiology and may be potentially modifiable. AIM: To review diet-gene interactions, aiming to further the understanding of the underlying biological pathways in CRC development. METHODS: The PubMed and Medline were systematically searched for prospective studies in relation to diet, colorectal cancer and genetics. RESULTS: In a meta-analysis, no interaction between NAT1 phenotypes and meat intake in relation to risk of CRC was found (P-value for interaction 0.95). We found a trend towards interaction between NAT2 phenotypes and meat intake in relation to risk of CRC. High meat intake was not associated with risk of CRC among carriers of the slow NAT2 phenotype, whereas NAT2 fast acetylators with high meat intake were at increased risk of CRC (OR = 1.25; 95% confidence interval (CI): 0.92-2.01) compared with slow acetylators with low meat intake (reference), P-value for interaction = 0.07. Low meat intake in the studied populations may influence the result. Interactions between meat, cruciferous vegetables, fibres, calcium, vitamins, and alcohol and ABCB1, NFKB1, GSTM1, GSTT1, CCND1, VDR, MGTM, IL10 and PPARG are suggested. CONCLUSIONS: A number of interactions between genetic variation and diet are suggested, but the findings need replication in independent, prospective, and well-characterised cohorts before conclusions regarding the underlying biological mechanisms can be reached. When the above criteria are met, studies on diet-gene interactions may contribute valuable insight into the biological mechanisms underlying the role of various dietary items in colorectal carcinogenesis.

Anderson, L., M. O'Rorke, et al. (2013). "Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland: new data from northern Ireland and a systematic review and meta-analysis." J Med Virol 85(2): 295-308.

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta-analysis pooling the prevalence of high-risk (HR-HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas(R) 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta-analysis was used to calculate a pooled HR-HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (+/-SD 11.9 years; range 20-64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high-grade cytological findings, respectively. Crude HR-HPV prevalence was 13.2% (95% CI, 12.7-13.7) among women with normal cytology and increased with cytological grade. In meta-analysis the pooled HR-HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10-0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02-0.05) and 0.01 (95% CI, 0.01-0.02), respectively. The findings of this Northern Ireland study and meta-analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type-specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR-HPV types other than HPV 16 and 18.

Anderson, P. A., A. B. Froyshteter, et al. (2013). "Meta-analysis of vertebral augmentation compared with conservative treatment for osteoporotic spinal fractures." J Bone Miner Res 28(2): 372-82.

Cement augmentation is a controversial treatment for painful vertebral compression fractures (VCF). Our research questions for the meta-analysis were: Is there a clinical and statistical difference in pain relief, functional improvement, and quality of life between conservative care and cement augmentation for VCF and, if so, are they maintained at longer time points? We conducted a search of MEDLINE from January 1980 to July 2011 using PubMed, Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE. Searches were performed from medical subject headings. Terms "vertebroplasty" and "compression fracture" were used. The outcome variables of pain, functional measures, health-related quality of life (HRQOL), and new fracture risk were analyzed. A random effects model was chosen. Continuous variables were calculated using the standardized mean difference comparing improvement from baseline of the experimental group with the control group. New vertebral fracture risk was calculated using log odds ratio. Six studies met the criteria. The pain visual analog scale (VAS) mean difference was 0.73 (confidence interval [CI] 0.35, 1.10) for early (<12 weeks) and 0.58 (CI 0.19, 0.97) for late time points (6 to 12 months), favoring vertebroplasty (p < 0.001). The functional outcomes at early and late time points were statistically significant with 1.08 (CI 0.33, 1.82) and 1.16 (CI 0.14, 2.18), respectively. The HRQOL showed superior results of vertebroplasty compared with conservative care at early and late time points of 0.39 (CI 0.16, 0.62) and 0.33 (CI 0.16, 0.51), respectively. Secondary fractures were not statistically different between the groups, 0.065 (CI -0.57, 0.70). This meta-analysis showed greater pain relief, functional recovery, and health-related quality of life with cement augmentation compared with controls. Cement augmentation results were significant in the early (<12 weeks) and the late time points (6 to 12 months). This meta-analysis provides strong evidence in favor of cement augmentation in the treatment of symptomatic VCF fractures.

Anderson-James, S., J. M. Marchant, et al. (2013). "Inhaled corticosteroids for subacute cough in children." Cochrane Database Syst Rev 2: CD008888.

BACKGROUND: Cough is the most common symptom presenting to primary healthcare services. Cough in children is associated with significant morbidity for both children and their parents. While inhaled corticosteroids (ICS) can potentially reduce cough associated with airway inflammation and airway hyper-reactivity, use of ICS in children is not without potential adverse effects. Therefore, it would be beneficial to clinical practice to evaluate the evidence for the efficacy of ICS in reducing the severity of cough in children with subacute cough (defined as cough duration of two to four weeks) systematically. OBJECTIVES: To evaluate the efficacy of ICS in reducing the severity of cough in children with subacute cough. SEARCH METHODS: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles were searched. The latest searches were performed in November 2011. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing ICS with a control group in children with subacute cough were considered for inclusion. DATA COLLECTION AND ANALYSIS: Search results were reviewed against pre-determined criteria for inclusion. Two sets of review authors independently selected, extracted and assessed the data for inclusion. Study authors were contacted for further information where required. Data were analysed as 'intention to treat'. MAIN RESULTS: The search identified 1178 potentially relevant titles; however, there were no published studies that were specifically designed to answer this question. Two studies met criteria for inclusion in the review and 98 children were included in the meta-analysis. There was no significant difference between groups in the proportion of children 'not cured' at follow-up (primary outcome measure), with a pooled odds ratio (OR) of 0.61 (95% confidence interval (CI) 0.24 to 1.55). However, the included studies were limited in their ability to answer the review question by the fact that all participants were infants, post acute bronchiolitis illness, and cough duration at the start of study medication was ill-defined. AUTHORS' CONCLUSIONS: There is currently no evidence to support the use of ICS for treatment of subacute cough in children. However, this systematic review is limited by the small number of studies available for analysis and the size, quality and design of these studies. Further well-designed RCTs are required to support or refute the efficacy of treatment with ICS in children with subacute cough.

Andrade, J. G., M. W. Deyell, et al. (2013). "Risk of bleeding on triple antithrombotic therapy after percutaneous coronary intervention/stenting: a systematic review and meta-analysis." Can J Cardiol 29(2): 204-12.

BACKGROUND: There are no reported randomized controlled trials of triple antithrombotic therapy (TT; aspirin plus a thienopyridine plus vitamin K antagonist) vs dual antiplatelet therapy (DAPT; aspirin plus a thienopyridine) among patients undergoing percutaneous coronary intervention with stenting (PCI-S). A systematic review and meta-analysis was undertaken to assess the risk of bleeding among patients receiving TT after PCI-S. METHODS: Electronic databases were searched for studies reporting bleeding among patients receiving TT after PCI-S. Of the 4108 articles screened, 18 met study inclusion criteria and underwent detailed data extraction: of these, 6 reported in-hospital outcomes, 14 reported 30-day outcomes, and 9 reported 6-month outcomes. At each time point, pooled estimates of bleeding with TT were ascertained and where possible summary odds ratios (ORs) for comparative risks vs DAPT were calculated. RESULTS: The pooled estimate of major bleeding rate with TT post PCI-S was 2.38% by 30 days postprocedure (95% confidence interval [CI], 0.98-3.77%) and 4.55% by 6 months postdischarge (95% CI, 0.56-8.53%). At 30 days and 6 months the rates of major bleeding with TT were significantly higher than those observed with DAPT: OR, 2.38 at 30 days (95% CI, 1.05-5.38) and OR, 2.87 at 6 months (95% CI, 1.47-5.62). CONCLUSIONS: This systematic review and meta-analysis of reports of triple therapy with a vitamin K antagonist, aspirin, and clopidogrel after PCI-S provides precise and valid bleeding risk data. Based on existing observational studies the rates of major and any bleeding associated with TT are clinically important and significantly greater than those reported with DAPT.

Andreassen, O. A., S. Djurovic, et al. (2013). "Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors." Am J Hum Genet 92(2): 197-209.

Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the "missing heritability" of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this "pleiotropic enrichment" by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors.

Andrews, J. and J. C. Pruessner (2013). "The Combined Propranolol/TSST Paradigm - A New Method for Psychoneuroendocrinology." PLoS One 8(2): e57567.

Upon perception of a stimulus as stressful, the human brain reacts with the activation of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), to mobilize energy resources to better cope with the stressor. Since the perception of the stressor is the initial stimulus, a synchronicity between the subjective perception of stress and the physiological stress reactivity should be expected. However, according to a recent meta-analysis, these associations are weak and inconsistent. The goal of the current study was to investigate the interaction between the SNS, HPA and subjective stress perceptions, by introducing an experimental manipulation of this interaction. For this purpose, we combined the SNS inhibitor propranolol with the Trier Social Stress Test, and measured endocrinological and psychological responses to the stressor. Thirty healthy male participants were recruited and randomly assigned to either a propranolol (PROP; n = 15) or placebo (PLC; n = 15) group. All subjects were administered 80 mg of propranolol 60 minutes prior to exposure to psychosocial stress. Salivary cortisol and alpha amylase (sAA), heart rate, blood pressure and subjective stress responses were assessed throughout the study. We observed significantly reduced sAA levels and heart rate increases in the PROP group in response to stress, with no effects of the drug on systolic or diastolic blood pressure changes. In line with previous studies, a significant increase in cortisol was seen in response to the stress exposure. Importantly, the cortisol increase was significantly higher in the PROP group. A typical increase in subjective stress could be seen in both groups, with no significant group differences emerging. Complementing previous work, this study further demonstrates a significant interaction between the HPA and the SNS during acute stress. The HPA activity was found to be elevated in the presence of a suppressed SNS in reactivity to the TSST.

Andrici, J., M. Tio, et al. (2013). "Hiatal hernia and the risk of Barrett's esophagus." J Gastroenterol Hepatol 28(3): 415-31.

Background and Aim: Barrett's esophagus has been associated with the presence of hiatal hernia; however, to date no meta-analysis of the relationship has been performed. We aimed to conduct a systematic review and meta-analysis, providing a quantitative estimate of the increased risk of Barrett's esophagus associated with hiatal hernia. Methods: A search was conducted through four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) to 4 April 2012, for observational studies of Barrett's esophagus patients. We calculated pooled odds ratios and 95% confidence intervals using a random effects model for the association of hiatal hernia with any length Barrett's esophagus, as well as with short segment Barrett's esophagus and long segment Barrett's esophagus. 33 studies comprising 4390 Barrett's esophagus patients were eligible for the meta-analysis. Results: Hiatal hernia was associated with an increased risk of Barrett's esophagus of any length (odds ratio 3.94; 95% confidence interval 3.02-5.13). Heterogeneity was present (I(2) = 82.03%, P < 0.001), and the Egger test for publication bias was significant (P = 0.0005). The short segment Barrett's esophagus subgroup analysis likewise showed an increased risk (odds ratio 2.87; 95% confidence interval 1.75-4.70). The strongest association was between hiatal hernia and long segment Barrett's esophagus (odds ratio 12.67; 95% confidence interval 8.33-19.25). The increased risk was present even after adjusting for reflux and body mass index. Conclusions: The presence of hiatal hernia was associated with an increased risk of Barrett's esophagus, even after adjusting for clinically significant confounders. The strongest association was found between hiatal hernia and long segment Barrett's esophagus.

Andrici, J., M. Tio, et al. (2013). "Meta-analysis: Barrett's oesophagus and the risk of colonic tumours." Aliment Pharmacol Ther 37(4): 401-10.

BACKGROUND: Barrett's oesophagus (BO) is a premalignant condition associated with oesophageal adenocarcinoma. Although speculation exists, it is currently unclear if BO is associated with an increased risk of colonic tumours. AIM: To conduct a meta-analysis of studies reporting the prevalence of colonic tumours in patients with BO vs. controls and thus quantify the risk of colonic tumours associated with BO. METHODS: A search was conducted through Medline, PubMed, Embase, and Current Contents Connect to 7 October 2012. We calculated pooled odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model for the risk of all colonic tumours associated with BO, as well as for the subgroups of colorectal cancer (CRC) and benign adenomatous tumours. RESULTS: In total, 11 studies, with 2580 BO cases, met our inclusion criteria. BO was associated with an increased risk of any colonic tumours (OR: 1.96; 95% CI: 1.56-2.46). BO was associated with an increased risk of benign adenomatous tumours (OR: 1.69; 95% CI: 1.20-2.39), as well as an increased risk of CRC (OR: 1.90; 95% CI: 1.35-2.67). No statistically significant heterogeneity was observed. Publication bias was not present. CONCLUSIONS: Barrett's oesophagus was associated with an increased risk of both benign adenomatous colonic tumours and colorectal cancer. Barrett's oesophagus had a stronger association with colorectal cancer than with benign colonic tumours. Further prospective cohort studies are needed to confirm the relationship.

Andrisano, C., A. Chiesa, et al. (2013). "Newer antidepressants and panic disorder: a meta-analysis." Int Clin Psychopharmacol 28(1): 33-45.

Selective serotonin reuptake inhibitors and venlafaxine are currently considered as first-line agents for patients with panic disorder (PD). However, a systematic comparison of newer antidepressants for the treatment of PD is lacking thus far. Eligible studies focusing on PD patients treated with newer antidepressants were entered in the Cochrane Collaboration Review Manager. Our primary outcome measure was the mean change in panic symptoms from the baseline to the endpoint in patients treated with antidepressants as compared with those treated with placebo. Secondary outcome measures included the mean change in the overall anxiety scores and dropout rates. Sensitivity analyses were also carried out. Fifty studies focusing on 5236 patients were included. The following antidepressants were significantly superior to placebo for PD patients with the following increasing order of effectiveness: citalopram, sertraline, paroxetine, fluoxetine, and venlafaxine for panic symptoms and paroxetine, fluoxetine, fluvoxamine, citalopram, venlafaxine, and mirtazapine for overall anxiety symptoms. Aside from reboxetine and fluvoxamine, all drugs were associated with significantly lower dropout rates as compared with placebo. Several clinical variables moderated clinical outcomes. However, because of some inconsistencies across the studies and limited evidence for some drugs under investigation, further head-to-head comparisons are required.

Anglin, R. E., Z. Samaan, et al. (2013). "Vitamin D deficiency and depression in adults: systematic review and meta-analysis." Br J Psychiatry 202: 100-7.

BACKGROUND: There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. AIMS: To determine the relationship, if any, between vitamin D deficiency and depression. METHOD: A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. RESULTS: One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23-0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49). CONCLUSIONS: Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.

Annweiler, C., D. J. Llewellyn, et al. (2013). "Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis." J Alzheimers Dis 33(3): 659-74.

Vitamin D has been investigated in association with cognitive function in older adults. It is unclear whether hypovitaminosis D could be associated with Alzheimer's disease (AD). Our objective was to systematically review and quantitatively synthesize the association of low serum 25-hydroxyvitamin D (25OHD) concentrations with AD in adults. A Medline and PsycINFO(R) search was conducted on May 2012, with no limit of date, using the MeSH terms "Vitamin D" OR "Hydroxycholecalciferols" combined with the MeSH terms "Alzheimer disease" OR "Dementia" OR "Cognition" OR "Cognition disorders" OR "Memory" OR "Memory Disorders" OR "Executive Function" OR "Attention" OR "Neuropsychological Tests". Of the 284 selected studies, 10 observational studies (including 9 case-controls and 1 cohort study) met the selection criteria. All were of good quality. The number of AD cases ranged from 20 to 211 (40%-100% female). Finally, 7 case-control studies were eligible for fixed and random-effects meta-analyses of bias-corrected effect size of the difference in serum 25OHD concentrations between AD cases and controls using an inverse-variance method. The pooled effect size in random-effects meta-analysis was 1.40 (95% CI: 0.26;2.54), a 'large' effect size that indicates that serum 25OHD concentrations were 1.4 standard deviation units lower in AD cases compared to cognitively healthy controls (p = 0.016). In conclusion, AD cases had lower serum vitamin D concentrations than matched controls. This reinforces the conceptualization of vitamin D as a 'neurosteroid hormone' and as a potential biomarker of AD.

Ansari, A. A., S. K. Ali, et al. (2013). "The Construct and Criterion Validity of the Mini-CEX: A Meta-Analysis of the Published Research." Acad Med 88(3): 413-20.

PURPOSE: To conduct a meta-analysis of published studies to determine the construct and criterion validity of the mini-clinical evaluation exercise (mini-CEX) to measure clinical performance. METHOD: The authors included all peer-reviewed studies published from 1995 to 2012 that reported the relationship between participants' performance on the mini-CEX and on other standardized academic and clinical performance measures. Moderator variables and performance and standardized exam measures were extracted and reviewed independently using a standardized coding protocol. RESULTS: Performance measures from 11 studies were identified. A random-effects model of weighted mean effect size differences (d) resulted in:(1) construct validity coefficients for the mini-CEX on the trainees' performance across different residency year levels ranging from d = 0.25 (95% confidence intervals [CI]: 0.04-0.46) to d = 0.50 (95% CI: 0.31-0.70), and(2) concurrent validity coefficients for the mini-CEX based on personnel ratings ranging from d = 0.23 (95% CI: 0.04-0.50) to d = 0.50 (95% CI: 0.34-0.65).Also, a random-effects model of weighted correlation effect size differences (r) resulted in predictive validity coefficients for the mini-CEX on trainees' performance across different standardized measures ranging from r = 0.26 (95% CI: 0.16-0.35) to r = 0.85 (95% CI: 0.47-0.96). CONCLUSIONS: The construct and criterion validity of the mini-CEX was supported by small to large effect size differences based on measures between trainees' achievement and clinical skills performance, indicating that it is an important instrument for the direct observation of trainees' clinical performance.

Antonarakis, G. S., K. Tsiouli, et al. (2013). "Mesiodistal tooth size in non-syndromic unilateral cleft lip and palate patients: a meta-analysis." Clin Oral Investig 17(2): 365-77.

OBJECTIVES: To evaluate, using meta-analysis methodology, mesiodistal tooth dimensions in non-syndromic unilateral cleft lip and palate (CLP) patients. MATERIALS AND METHODS: A literature search was conducted using PubMed, Medline, Google Scholar Beta, EMBASE Excerpta Medica, CINAHL, Web of Science, and the Cochrane Collaboration, identifying English and non-English articles reporting on mesiodistal tooth dimensions on the cleft and non-cleft side of non-syndromic unilateral CLP patients. Additional studies were identified by searching reference lists of articles consulted. Only studies with a suitable control group were included. Two examiners independently performed the literature search and data extraction. Using meta-analysis software, data extracted from each selected study were statistically combined using the fixed-effects model. Weighted mean differences, 95 % confidence intervals, and heterogeneity were calculated for each measurement. RESULTS: Four articles fulfilling the inclusion criteria were located and included in the meta-analysis. Maxillary incisors and first molars were found to be significantly larger on the non-cleft side while mandibular incisors and premolars were larger on the cleft side, in non-syndromic unilateral CLP patients. On the cleft side, maxillary premolars and second molars were larger in cleft than control patients while incisors were smaller, whereas all mandibular teeth were larger in cleft patients. On the non-cleft side, all maxillary teeth except for the central incisors were larger in the cleft than control patients, while all mandibular teeth were larger in the cleft patients except for lateral incisors. CONCLUSIONS: Non-syndromic unilateral CLP patients tend to have larger posterior but smaller anterior teeth compared with the general population. Comparing sides, unilateral CLP patients tend to have smaller maxillary but larger mandibular teeth on the cleft than on the non-cleft side. CLINICAL RELEVANCE: Given that obtaining a stable, functional, and esthetic occlusion requires a thorough evaluation of tooth size, knowledge about trends in tooth size variations in CLP patients can help with dental and orthodontic treatment planning.

Antoni, S., A. J. Sasco, et al. (2013). "Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis." Breast Cancer Res Treat 137(2): 337-47.

Mammographic density (MD) is a strong marker of breast cancer risk, but it is debated whether the association holds, and is of a similar magnitude, for different subtypes of breast cancer defined by receptor status or gene expression profiles. A literature search conducted in June 2012 was used to identify all studies that had investigated the association of MD with subtype-specific breast cancer, independent of age. 7 cohort/case-control and 12 case-only studies were included, comprising a total of >24,000 breast cancer cases. Random effects meta-analysis models were used to combine relative risks (RR) of MD with subtype-specific breast cancer for case-control studies, and in case-only studies to combine relative risk ratios (RRR) of receptor positive versus negative breast tumors. In case-control/cohort studies, relative to women in the lowest density category, women in the highest density category had 3.1-fold (95 % confidence interval [CI] 2.2, 4.2) and 3.2-fold (1.7, 5.9) increased risk of estrogen receptor positive (ER+) and ER- breast cancer, respectively. In case-only analyses, RRRs of breast tumors being ER+ versus ER- were 1.13 (95 % CI 0.89, 1.42) for medium versus minimal MD. MD remained associated with screen-detected ER+ tumors, despite the expectation of this association to be attenuated due to masking bias and overdiagnoses of ER+ tumors. In eight contributing studies, the association of MD did not differ by HER2 status. This combined evidence strengthens the importance of MD as a strong marker of overall and of subtype-specific risk, and confirms its value in overall breast cancer risk assessment and monitoring for both research and clinical purposes.

Antoniou, G. A., N. Chalmers, et al. (2013). "A meta-analysis of endovascular versus surgical reconstruction of femoropopliteal arterial disease." J Vasc Surg 57(1): 242-53.

BACKGROUND: Controversy exists as to the relative merits of surgical and endovascular treatment of femoropoliteal arterial disease. METHODS: A systematic review of the literature was undertaken to identify studies comparing open surgical and percutaneous transluminal methods for the treatment of femoropopliteal arterial disease. Outcome data were pooled and combined overall effect sizes were calculated using fixed or random effects models. RESULTS: Four randomized controlled trials and six observational studies reporting on a total of 2817 patients (1387 open, 1430 endovascular) were included. Endovascular treatment was accompanied by lower 30-day morbidity (odds ratio [OR], 2.93; 95% confidence interval [CI], 1.34-6.41) and higher technical failure (OR, 0.10; 95% CI, 0.05-0.22) than bypass surgery, whereas no differences in 30-day mortality between the two groups were identified (OR, 0.92; 95% CI, 0.55-1.51). Higher primary patency in the surgical treatment arm was found at 1 (OR, 2.42; 95% CI, 1.37-4.28), 2 (OR, 2.03; 95% CI, 1.20-3.45), and 3 (OR, 1.48; 95% CI, 1.12-1.97) years of intervention. Progression to amputation was found to occur more commonly in the endovascular group at the end of the second (OR, 0.60; 95% CI, 0.42-0.86) and third (OR, 0.55; 95% CI, 0.39-0.77) year of intervention. Higher amputation-free and overall survival rates were found in the bypass group at 4 years (OR, 1.31; 95% CI, 1.07-1.61 and OR, 1.29; 95% CI, 1.04-1.61, respectively). CONCLUSIONS: High-level evidence demonstrating the superiority of one method over the other is lacking. An endovascular-first approach may be advisable in patients with significant comorbidity, whereas for fit patients with a longer-term perspective a bypass procedure may be offered as a first-line interventional treatment.

Antoniou, G. A., G. S. Georgiadis, et al. (2013). "A meta-analysis of outcomes of endovascular abdominal aortic aneurysm repair in patients with hostile and friendly neck anatomy." J Vasc Surg 57(2): 527-38.

BACKGROUND: An increasing number of abdominal aortic aneurysms with unfavorable proximal neck anatomy are treated with standard endograft devices. Skepticism exists with regard to the safety and efficacy of this practice. METHODS: A systematic review of the literature was undertaken to identify all studies comparing the outcomes of endovascular aneurysm repair (EVAR) in patients with hostile and friendly infrarenal neck anatomy. Hostile neck conditions were defined as conditions that were not consistent with the instructions for use of the endograft devices employed in the selected studies. Outcome data were pooled, and combined overall effect sizes were calculated using fixed or random effects models. RESULTS: Seven observational studies reporting on 1559 patients (hostile anatomy group, 714 patients; friendly anatomy group, 845 patients) were included. Patients with hostile anatomy required an increased number of adjunctive procedures to achieve proximal seal compared with patients with friendly anatomy (odds ratio [OR], 3.050; 95% confidence interval [CI], 1.884-4.938). Although patients with unfavorable neck anatomy had an increased risk of developing 30-day morbidity (OR, 2.278; 95% CI, 1.025-5.063), no significant differences in the incidence of type I endoleak and reintervention rates within 30 days of treatment between the two groups were identified (OR, 2.467 and 1.082; 95% CI, 0.562-10.823 and 0.096-12.186). Patients with hostile anatomy had a fourfold increased risk of developing type I endoleak (OR, 4.563; 95% CI, 1.430-14.558) and a ninefold increased risk of aneurysm-related mortality within 1 year of treatment (OR, 9.378; 95% CI, 1.595-55.137). CONCLUSIONS: Insufficient high-level evidence for or against performing standard EVAR in patients with hostile neck anatomy exists. Our analysis suggests EVAR should be cautiously used in patients with anatomic neck constraints.

Antoniou, S. A., G. A. Antoniou, et al. (2013). "Blunt versus bladed trocars in laparoscopic surgery: a systematic review and meta-analysis of randomized trials." Surg Endosc.

BACKGROUND: Trocar-associated visceral injuries are rare but potentially fatal complications of laparoscopic access. More commonly, abdominal wall bleeding occurs, which usually requires hemostatic measures and prolongs operative time. Blunt-tipped trocars have been postulated to carry a lower risk of abdominal wall bleeding and intra-abdominal injuries. The aim of the present systematic review and meta-analysis was to comparatively evaluate the relative risks of abdominal wall bleeding, visceral injuries, and overall complications with the use of bladed and blunt-tipped laparoscopic trocars. METHODS: The databases of Medline, EMBASE, and the Cochrane Central Register of Randomized Trials were searched to identify randomized studies that compared trocar-associated complications with the use of blunt and bladed trocars. Primary outcome measure was the relative risk of abdominal wall trocar site bleeding, and secondary outcome measures included visceral injuries and overall complications. Outcome data were pooled and combined overall effect sizes were calculated using the fixed- or random-effects model. RESULTS: Eight eligible randomized trials were identified; they included 720 patients with a median Jadad score of 4. The incidence of abdominal wall bleeding for the blunt and the bladed trocar group was 3 and 9 %, respectively [odds ratio (OR) 0.42, 95 % confidence interval (CI) 0.21-0.88]. Trocar-associated morbidity rate, excluding bleeding events of the abdominal wall, was documented at 0.2 and 0.7 % of the blunt and the bladed trocar arm, respectively (OR 0.43, 95 % CI 0.06-2.97). The overall trocar-associated morbidity rate was 3 % in the blunt trocar group and 10 % in the bladed trocar group (OR 0.38, 95 % CI 0.19-0.77). CONCLUSIONS: Reliable data support a lower relative risk of trocar site bleeding and overall complications with blunt laparoscopic cannulas than bladed trocars. Transition to blunt trocars for secondary cannulation of the abdominal wall is thus strongly recommended. Larger patient populations are required to estimate the relative risk of visceral injuries.

Antunes-Martins, A., J. R. Perkins, et al. (2013). "Systems biology approaches to finding novel pain mediators." Wiley Interdiscip Rev Syst Biol Med 5(1): 11-35.

Chronic pain represents a major health burden; this maladaptive pain state occurs as a consequence of hypersensitivity within the peripheral and central components of the somatosensory system. High throughput technologies (genomics, transciptomics, lipidomics, and proteomics) are now being applied to tissue derived from pain patients as well as experimental pain models to discover novel pain mediators. The use of clustering, meta-analysis and other techniques can help refine potential candidates. Of particular importance are systems biology methods, such as co-expression network generating algorithms, which infer potential associations/interactions between molecules and build networks based on these interactions. Protein-protein interaction networks allow the lists of potential targets generated by these different platforms to be analyzed in their biological context. Outputs from these different methods must also be related to the clinical pain phenotype. The improved and standardized phenotyping of pain symptoms and sensory signs enables much better subject stratification. Our hope is that, in the future, the use of computational approaches to integrate datasets including sensory phenotype as well as the outputs of high throughput technologies will help define novel pain mediators and provide insights into the pathogenesis of chronic pain.

Anuradha, C., K. S. Jacob, et al. (2013). "Evidence-based practice in radiology: Knowledge, attitude and perceived barriers to practice among residents in radiology." Eur J Radiol.

AIM: We examinted the attitude, knowledge and perceived barriers to evidence-based practice of radiology (EBPR) among residents in radiology. STUDY DESIGN AND SETTING: We used the McColl questionnaire (1) and the BARRIERS scale (2) to assess the issues among radiology trainees attending an annual refresher course. Ninety six residents from 32 medical colleges from Southern India attended the course. RESULTS: Eighty (83.3%) residents, 55 male and 25 female of age range 24-34 years, consented and returned the questionnaire. The majority of the participants had a positive attitude towards EBPR. However, 45% were unaware of sources for evidence based literature although many had access to Medline (45%) and the internet (80%). The majority (70%) were aware of the common technical terms (e.g. odds ratio, absolute and relative risk) but other complex details (e.g. meta-analysis, clinical effectiveness, confidence interval, publication bias and number needed to treat) were poorly understood. Though majority of residents (59%) were currently following guidelines and protocols laid by colleagues within their departments, 70% of residents were interested in learning the skills of EBPR and were willing to appraise primary literature or systematic reviews by themselves. Insufficient time on the job to implement new ideas (70.1%); relevant literature is not being complied in one place (68.9%); not being able to understand statistical methods (68.5%) were considered to be the major barriers to EBPR. Training in critical appraisal significantly influence usage of bibliographic databases (p<0.0001). Attitude of collegues (p=0.006) influenced attitude of the trainees towards EBPR. Those with higher knowledge scores (p=0.02) and a greater awareness of sources for seeking evidence based literature (p=0.05) held stronger beliefs that EBPR significantly improved patient care. CONCLUSIONS: The large knowledge gap related to EBPR suggests the need to incorporate structured training into the core-curriculum of training programmes in radiology.

Apfel, C. C., A. Turan, et al. (2013). "Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and meta-analysis." Pain.

Opioids are a key risk factor for postoperative nausea and vomiting (PONV). As intravenous (i.v.) acetaminophen reduces postoperative pain and opioid requirements, one would expect i.v. acetaminophen to be associated with a lower incidence of opioid-induced side effects, including PONV. We conducted a systematic search using Medline and Cochrane databases supplemented with hand search of abstract proceedings to identify randomized-controlled trials of i.v. acetaminophen. Inclusion criteria were (a) randomized for i.v. acetaminophen vs a placebo control, (b) general anesthesia, and (c) reported or obtainable PONV outcomes. Primary outcome was postoperative nausea and secondary outcome was postoperative vomiting. We included 30 studies with 2364 patients (1223 in the acetaminophen group, 1141 in the placebo group). The relative risk (95% confidence interval) was 0.73 (0.60-0.88) for nausea and 0.63 (0.45-0.88) for vomiting. Data showed significant heterogeneity for both nausea (P=0.02, I(2)=38%) and vomiting (P=0.006, I(2)=47%), but were homogeneous when studies were grouped according to timing of first administration: i.v. acetaminophen reduced nausea when given prophylactically either before surgery, 0.54 (0.40-0.74), or before arrival in the postanesthesia care unit, 0.67 (0.55-0.83); but not when given after the onset of pain, 1.12 (0.85-1.48). When i.v. acetaminophen was given prophylactically, the reduction of nausea correlated with the reduction of pain (odds ratio 0.66, 0.47-0.93), but not with reduction in postoperative opioids (odds ratio 0.89, 0.64-1.22). Prophylactically administered i.v. acetaminophen reduced PONV, mainly mediated through superior pain control.

Aradi, D., A. Komocsi, et al. (2013). "Impact of clopidogrel and potent P2Y 12 -inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: a systematic review and meta-analysis." Thromb Haemost 109(1): 93-101.

Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.

Aranda-Gallardo, M., J. M. Morales Asencio, et al. (2013). "Instruments for assessing the risk of falls in acute hospitalized patients: a systematic review protocol." J Adv Nurs 69(1): 185-93.

AIM: The purpose of this article is to present the research protocol of a systematic review about fall risk assessment tools in acute hospitalized patients. BACKGROUND: Various risk assessment tools for falls have been developed, but with uncertainties derived from validation in heterogeneous environments and variations in their sensitivity, specificity and predictive validity. DESIGN: Systematic review and meta-analysis. METHODS: Two independent reviewers will extract data in a blinded process. Quality of studies will be assessed using various standardized instruments. A meta-analysis will be performed if applicable. For all studies, sensitivity, specificity, positive and negative predictive values, together with the positive and negative likelihood ratios and Youden index will be calculated. The diagnostic odds ratio of the studies and the hierarchical summary Relative Operating Characteristic curve and bivariate model will be applied. Calculations will be made from random effects models. Forest-plot diagrams for sensitivity and specificity and likelihood ratios, in addition to Cochrane's Q test and the I(2) statistic, will be calculated. Funding of the review was confirmed in December 2010. DISCUSSION: The results of this review will help to clarify some uncertainties provoked by earlier research findings and enable informed choice of a validated, reproducible instrument for assessing the risk of falls by hospital patients, so that preventive action may be taken to minimize this risk.

Arbyn, M., J. Roelens, et al. (2013). "The APTIMA HPV assay versus the Hybrid Capture 2 test in triage of women with ASC-US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy." Int J Cancer 132(1): 101-8.

Testing for DNA of 13 high-risk HPV types with the Hybrid Capture 2 (HC2) test has consistently been shown to perform better in triage of women with cervical cytology results showing atypical squamous cells of undetermined significance (ASC-US) but often not in triage of low-grade squamous intraepithelial lesions (LSIL) detected in cervical cancer screening. In a meta-analysis, we compared the accuracy of the APTIMA HPV test, which identifies RNA of 14 high-risk HPV types, to HC2 for the triage of women with ASC-US or LSIL. Literature search-targeted studies where the accuracy of APTIMA HPV and HC2 for detection of underlying CIN2/3+ was assessed concomitantly including verification of all cases of ASC-US and LSIL. HSROC (Hierarchical Summary ROC) curve regression was used to compute the pooled absolute and relative sensitivity and specificity. Eight studies, comprising 1,839 ASC-US and 1,887 LSIL cases, were retrieved. The pooled sensitivity and specificity of APTIMA to triage ASC-US to detect underlying CIN3 or worse was 96.2% (95% CI = 91.7-98.3%) and 54.9% (95% CI = 43.5-65.9%), respectively. APTIMA and HC2 showed similar pooled sensitivity; however, the specificity of the former was significantly higher (ratio: 1.19; 95% CI = 1.08-1.31 for CIN2+). The pooled sensitivity and specificity of APTIMA to triage LSIL were 96.7% (95% CI = 91.4-98.9%) and 38.7% (95% CI = 30.5-47.6%) for CIN3+. APTIMA was as sensitive as HC2 but more specific (ratio: 1.35; 95% CI = 1.11-1.66). Results were similar for detection of CIN2 or worse. In both triage of ASC-US and LSIL, APTIMA is as sensitive but more specific than HC2 for detecting cervical precancer.

Arezzo, A., G. Scozzari, et al. (2013). "Is single-incision laparoscopic cholecystectomy safe? Results of a systematic review and meta-analysis." Surg Endosc.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is gaining popularity. It is not evident whether the benefits of this procedure overcome the potential increased risk. We performed a systematic review and meta-analysis to compare SILC with conventional multi-incision laparoscopic cholecystectomy (MILC). METHODS: Data from randomized, controlled trials published up to December 2011 and comparing SILC versus MILC were extracted. The primary end point was overall morbidity. A fixed-effect model was applied to summarize the study outcomes in the meta-analysis, and a random-effect model was used in the sensitivity analysis. The outcome measures were relative risk (RR) and mean difference (MD); a RR of <1.0 or a negative MD indicated a more favorable outcome after SILC. Publication bias was assessed by a funnel plot, and heterogeneity was tested by the I (2) measure and subgroup analyses. RESULTS: A total of 12 trials (996 patients) were included. Mortality was nil in both treatment groups; the overall RR for morbidity was 1.36 (p = 0.098). The mean operating time was 47.2 min for MILC and 58.1 min for SILC (MD 9.47 min; p < 0.001). The visual analog scale pain score at 24 h after surgery was 2.96 in MILC and 2.34 in SILC (MD -0.64; p = 0.058), but sensitivity analysis of the four studies deemed at low risk of bias for pain assessment, according to blinding and postoperative analgesic protocols, showed significance at -0.43 points (95 % confidence interval -0.87 to 0.00; p = 0.049). Cosmetic outcome scored better in the SILC group, with its standardized MD being equal to 1.16 (95 % confidence interval 0.57 to 1.75; p < 0.001). CONCLUSIONS: In selected patients, SILC has similar overall morbidity compared with MILC; further, it results in better cosmetic satisfaction and reduced postoperative pain despite longer operative time.

Armstrong, A. W., C. T. Harskamp, et al. (2013). "Psoriasis and metabolic syndrome: A systematic review and meta-analysis of observational studies." J Am Acad Dermatol.

BACKGROUND: Increasing population-based studies have suggested a relationship between psoriasis and metabolic syndrome. OBJECTIVE: The objective of this study was to perform a systematic review and meta-analysis that synthesizes the epidemiologic associations between psoriasis and metabolic syndrome. METHODS: We searched for observational studies from MEDLINE, EMBASE, and Cochrane Central Register from Jan 1, 1980 to Jan 1, 2012. We applied the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines in the conduct of this study. RESULTS: We identified 12 observational studies with a total of 1.4 million study participants fulfilling the inclusion criteria, among whom 41,853 were patients with psoriasis. Based on random-effects modeling of cross-sectional and case-controlled studies, the pooled odds ratio (OR) for metabolic syndrome among patients with psoriasis was 2.26 (95% confidence interval [CI] 1.70-3.01) compared with the general population. Visual inspection of a funnel plot and formal analysis with the Egger test suggested publication bias and absence of small studies in the published literature (P = .03). A dose-response relationship was also observed between psoriasis severity and prevalence of metabolic syndrome. LIMITATIONS: No studies to date have assessed incidence of metabolic syndrome among patients with psoriasis. CONCLUSIONS: Compared with the general population, psoriasis patients have higher prevalence of metabolic syndrome, and patients with more severe psoriasis have greater odds of metabolic syndrome than those with milder psoriasis.

Armstrong, A. W., C. T. Harskamp, et al. (2013). "Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis." JAMA Dermatol 149(1): 84-91.

OBJECTIVE: To compare the prevalence and incidence of type 2 diabetes mellitus between patients with psoriasis and those without psoriasis. DATA SOURCES: MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews between January 1, 1980, and January 1, 2012. STUDY SELECTION: Observational (cohort, case-control, and cross-sectional) studies published in English that compared the prevalence or incidence of diabetes among patients with psoriasis with individuals serving as controls. DATA EXTRACTION: Two independent investigators extracted the data. The quality of evidence was assessed using a 6-point scale. DATA SYNTHESIS: Among 142 identified publications, 27 observational studies were included in the meta-analysis. Five of these studies assessed the incidence of diabetes in patients with psoriasis and were analyzed separately. Among studies assessing the prevalence, psoriasis was associated with an odds ratio (OR) of 1.59 (95% CI, 1.38-1.83) for diabetes. The pooled OR was 1.53 (95% CI, 1.16-2.04) for mild psoriasis and 1.97 (1.48-2.62) for severe psoriasis. Meta-regression of prespecified potential sources of heterogeneity revealed a nonsignificant difference (P= .10) of increased reported strength of association among studies that used medical record review (OR, 1.52 [95% CI, 1.31-1.77]) or patients' report of diabetes (2.79 [1.42-5.48]) compared with studies that used billing data (1.46 [1.01-2.09]). Among studies that assessed incidence, psoriasis was associated with a relative risk of 1.27 (95% CI, 1.16-1.40) for developing diabetes. CONCLUSIONS: Psoriasis is associated with an increased prevalence and incidence of diabetes. The association of psoriasis with diabetes may be strongest among patients with severe psoriasis.

Armstrong, M. J., D. D. Houlihan, et al. (2013). "Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program." Aliment Pharmacol Ther 37(2): 234-42.

BACKGROUND: Non-alcoholic fatty liver disease has reached epidemic proportions in type 2 diabetes (T2D). Glucagon-like peptide-1 analogues are licensed in T2D, yet little data exist on efficacy and safety in liver injury. AIM: To assess the safety and efficacy of 26-week liraglutide on liver parameters in comparison with active-placebo. METHODS: Individual patient data meta-analysis was performed using patient-level data combined from six 26-week, phase-III, randomised controlled T2D trials, which comprise the 'Liraglutide Effect and Action in Diabetes' (LEAD) program. The LEAD-2 sub-study was analysed to assess the effect on CT-measured hepatic steatosis. RESULTS: Of 4442 patients analysed, 2241 (50.8%) patients had an abnormal ALT at baseline [mean ALT 33.8(14.9) IU/L in females; 47.3(18.3) IU/L in males]. Liraglutide 1.8 mg reduced ALT in these patients vs. placebo (-8.20 vs. -5.01 IU/L; P = 0.003), and was dose-dependent (no significant differences vs. placebo with liraglutide 0.6 or 1.2 mg). This effect was lost after adjusting for liraglutide's reduction in weight (mean ALT difference vs. placebo -1.41 IU/L, P = 0.21) and HbA1c (+0.57 IU/L, P = 0.63). Adverse effects with 1.8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In LEAD-2 sub-study, liraglutide 1.8 mg showed a trend towards improving hepatic steatosis vs. placebo (liver-to-spleen attenuation ratio +0.10 vs. 0.00; P = 0.07). This difference was reduced when correcting for changes in weight (+0.06, P = 0.25) and HbA(1c) (0.00, P = 0.93). CONCLUSIONS: Twenty-six weeks' liraglutide 1.8 mg is safe, well tolerated and improves liver enzymes in patients with type 2 diabetes. This effect appears to be mediated by its action on weight loss and glycaemic control.

Arnaiz-Villena, A., M. Fernandez-Honrado, et al. (2013). "Amerindians show no association of PPAR-gamma2 gene Ala12 allele and obesity: an "unthrifty" variant population genetics." Mol Biol Rep 40(2): 1767-74.

Obesity is for many scholars the most important starting status that gives rise to Metabolic Syndrome (MS) and Type 2 Diabetes (T2D). In the present paper, a genetically homogeneous Amerindian population, as defined by HLA genes, has been genotyped for one of the MS and T2D predisposing genes: PPAR-gamma Ala12 and Pro 12 variants. Ala12 has been negatively associated with obesity, but other authors do not find such an association. Notwithstanding, a meta-analysis that used many subjects clearly demonstrated that PPAR-gamma Ala12 bearing ones had a reduced risk for T2D. Our results show that Amerindians do not have association of PPAR-gamma2 Ala12 and obesity; the latter was measured by waist circumference values after taken specific Amerindian normal waist parameters. Also, a population genetics study indicates that Pro12 allele was the wild allele, which must have occurred before modern humans left Africa. Ala12 may have appeared in Caucasoids later on, according to our comparisons. Negroids tend to show low or null Ala 12 allele frequencies, while most other populations have a significant frequency, particularly European Caucasoids. This may suggest that appearance of Ala12 allele occurred after populations adapted to an agricultural feeding.

Arsenault, K. A., A. M. Yusuf, et al. (2013). "Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery." Cochrane Database Syst Rev 1: CD003611.

BACKGROUND: Atrial fibrillation is a common post-operative complication of cardiac surgery and is associated with an increased risk of post-operative stroke, increased length of intensive care unit and hospital stays, healthcare costs and mortality. Numerous trials have evaluated various pharmacological and non-pharmacological prophylactic interventions for their efficacy in preventing post-operative atrial fibrillation. We conducted an update to a 2004 Cochrane systematic review and meta-analysis of the literature to gain a better understanding of the effectiveness of these interventions. OBJECTIVES: The primary objective was to assess the effects of pharmacological and non-pharmacological interventions for preventing post-operative atrial fibrillation or supraventricular tachycardia after cardiac surgery. Secondary objectives were to determine the effects on post-operative stroke or cerebrovascular accident, mortality, cardiovascular mortality, length of hospital stay and cost of treatment during the hospital stay. SEARCH METHODS: We searched the Cochrane Central Register of ControlLed Trials (CENTRAL) (Issue 8, 2011), MEDLINE (from 1946 to July 2011), EMBASE (from 1974 to July 2011) and CINAHL (from 1981 to July 2011). SELECTION CRITERIA: We selected randomized controlled trials (RCTs) that included adult patients undergoing cardiac surgery who were allocated to pharmacological or non-pharmacological interventions for the prevention of post-operative atrial fibrillation or supraventricular tachycardia, except digoxin, potassium (K(+)), or steroids. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted study data and assessed trial quality. MAIN RESULTS: One hundred and eighteen studies with 138 treatment groups and 17,364 participants were included in this review. Fifty-seven of these studies were included in the original version of this review while 61 were added, including 27 on interventions that were not considered in the original version. Interventions included amiodarone, beta-blockers, sotalol, magnesium, atrial pacing and posterior pericardiotomy. Each of the studied interventions significantly reduced the rate of post-operative atrial fibrillation after cardiac surgery compared with a control. Beta-blockers (odds ratio (OR) 0.33; 95% confidence interval) CI 0.26 to 0.43; I(2) = 55%) and sotalol (OR 0.34; 95% CI 0.26 to 0.43; I(2) = 3%) appear to have similar efficacy while magnesium's efficacy (OR 0.55; 95% CI 0.41 to 0.73; I(2) = 51%) may be slightly less. Amiodarone (OR 0.43; 95% CI 0.34 to 0.54; I(2) = 63%), atrial pacing (OR 0.47; 95% CI 0.36 to 0.61; I(2) = 50%) and posterior pericardiotomy (OR 0.35; 95% CI 0.18 to 0.67; I(2) = 66%) were all found to be effective. Prophylactic intervention decreased the hospital length of stay by approximately two-thirds of a day and decreased the cost of hospital treatment by roughly $1250 US. Intervention was also found to reduce the odds of post-operative stroke, though this reduction did not reach statistical significance (OR 0.69; 95% CI 0.47 to 1.01; I(2) = 0%). No significant effect on all-cause or cardiovascular mortality was demonstrated. AUTHORS' CONCLUSIONS: Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach.

Arulkumaran, N., N. M. Annear, et al. (2013). "Patients with end-stage renal disease admitted to the intensive care unit: systematic review." Br J Anaesth 110(1): 13-20.

The number of patients with end-stage renal disease (ESRD) is increasing worldwide, with a growing demand on healthcare services. A systematic review of the literature was performed to determine the requirement for intensive care unit (ICU) services, reasons for admission, predictors of mortality, and short- and long-term outcomes of ESRD patients admitted to ICU. Sixteen studies were identified, comprising 6591 ICU admissions. Cardiovascular disease and sepsis accounted for the majority of admissions. Acute illness severity scores tend to overestimate mortality among ESRD patients. Critical illness associated with acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with significantly higher hospital mortality compared with ESRD patients admitted to the ICU [odds ratio (OR) 3.9; 3.5-4.4; P<0.0001]. However, hospital mortality of ESRD patients is less favourable compared with matched patients with mild AKI (OR 1.5; 1.4-1.6; P<0.0001). Although the mortality rate remains high shortly after hospital discharge, the duration of increased mortality risk is unclear. Patients with ESRD frequently benefit from ICU admission, despite chronic co-morbidity. Further studies are required to modify and validate existing illness severity scores for ESRD patients admitted to the ICU, and to establish the duration of increased mortality risk after discharge from ICU.

Arya, R., F. T. Mangano, et al. (2013). "Adverse events related to extraoperative invasive EEG monitoring with subdural grid electrodes: A systematic review and meta-analysis." Epilepsia.

PURPOSE: Implantation of subdural grids and invasive electroencephalography (EEG) monitoring is important to define the ictal-onset zone and eloquent cortex in selected patients with medically refractory epilepsy. The objective of this systematic review is to summarize data about adverse events related to this procedure. METHODS: English-language studies published up to July 2012, reporting such adverse events were reviewed. Outcome measures included demographic variables; surgical protocol including number of subdural electrodes implanted per patient, duration of monitoring, antibiotic, and steroid prophylaxis; and adverse events. KEY FINDINGS: Twenty-one studies were identified including a total of 2,542 patients. The reported mean number of electrodes per patient and duration of monitoring varied from 52 to 95 and 5 to 17 days, respectively. There is a trend toward more uniform use of antibiotics and steroids in the perioperative period. Neurologic infections (pooled prevalence 2.3%, 95% confidence interval 1.5-3.1), superficial infections (3.0%, 1.9-4.1), intracranial hemorrhage (4.0%, 3.2-4.8), and elevated intracranial pressure (2.4%, 1.5-3.3) were found to be the most common adverse events. Up to 3.5% of patients required additional surgical procedure(s) for management of these adverse events. Increased number of electrodes (>/=67) was found to be independently associated with increased incidence of adverse events. SIGNIFICANCE: Although providing critical information for patients with medically refractory epilepsy, subdural grids implantation and invasive EEG monitoring entails risks of infection, hemorrhage, and elevated intracranial pressure. The prevalence estimates, likely to be conservative due to selective reporting, are expected to be helpful in counseling patients.

Asari, R., M. Riegler, et al. (2013). "Extending Barrett's esophagus cancer risk profile towards genetic abnormalities." Mol Cytogenet 6(1): 10.

Dear Editor, with interest we read the article by Bajpai et al. (1), entitled Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett's epithelium", which has been published in the recent issue of Molecular Cytogenetics. Barrett's esophagus results from gastroesophageal reflux and harbors an increased risk for the development of esophageal adenocarcinoma (0.5% annual cancer risk) (2,3). Using a fascinating in vitro approach the authors modeled the effect of gastroesophageal reflux on immortalized Barrett's esophagus cells (1). Bajpai et al. found that intermittent exposure of BAR-T cells to acid and bile for 18 to 78 weeks caused a spectrum of genetic abnormalities typical for cancer development, including polyploidy, loss of chromosomes and the development of transformed clones. In addition, the genetic changes evoked by acid and bile exposure format the target protein receptors for tumor stimulating growth factors, i.e. epidermal growth factor (EGF), which are known to promote the growth of gastrointestinal cancers (4). In contrast, unexposed cells did not exhibit these abnormalities. Remains to be questioned, if the striking observations made by the authors may be of clinical relevance for the diagnosis and the therapy of Barrett's esophagus? Conceptually, Barrett's esophagus results as the consequence of a complex neurohumoral response of the esophageal mucosa to gastroesophageal reflux including acid and bile (2,3). Thus, by theory, the removal of Barrett's tissue and the elimination of reflux should contribute to cancer prevention. Going in line with with this notion, recent studies found that elimination of reflux by effective antireflux surgery contributes to increase the yield of radiofrequency ablation to eradicate Barrett's esophagus, when compared to ablation and post-ablational proton pump inhibitor (PPI) therapy, which solely changes the pH of the reflux, but not the reflux per se (3,5). Given that the genetic abnormalities assessed by Bajpai et al. (1) can be visualized by modern endoscopic in vivo staining techniques, this may enable us to detect tissue at risk for cancer development (4,6,7) and specifically target our therapies (i.e. ablation, endoscopic resection) towards these areas (3). Therefore a risk profile- (anamnestic, demographic & endoscopic, esophageal function tests characteristics) (3) and endoscopically visualized genetic profile- based tailored management of Barrett's esophagus for cancer prevention may be realistic in the future (1,4,6,7). Thus, Barrett's positive individuals with increased reflux due to severely impaired function of the esophagus may be offered elimination of acid and bile reflux by an effective anti reflux surgery prior to ablation (3,5). In contrast, ablation and subsequent PPI therapy seems reasonable for those with Barrett's esophagus and normal esophageal function and reflux monitoring (3). Endoscopic radiofrequency ablation would then be targeted to in vivo staining positive genetic abnormal areas (1,6,7). Taken together, time seems ready to design prospective clinical trials to assess the impact of the above mentioned biological markers for cancer prevention. Sincerely, Reza Asari, Martin Riegler, Sebastian Schoppmann. Authors Reza Asari, Martin Riegler, Sebastian Schoppmann. Univ. Clinic of Surgery Medical University Vienna Vienna General Hospital Waehringer Guertel 18-20. References: 1. Bajpai M, Aviv H, Das KM. Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett's epithelium. Mol Cytogen 2012; 5:43. ahead of print. 2. Mesteri I, Lenglinger J, Beller L, Fischer-See S, Schoppmann SF, Wrba F, Riegler M, Zacherl J. Assessment of columnar-lined esophagus in controls and patients with gastroesophageal reflux disease with and without proton-pump inhibitor therapy. Eur Surg 2012; 44: 304-313. 3. Mesteri I, Beller S, Fischer-See S, Schoppmann SF, Lenglinger J, Wrba F, RIegler M, Zacherl J. Radiofrequency ablation of Barrett's esophagus and early cancer within the background of the pathophysiology of the disease. Eur Surg 2012; 6 (ahead of print). 4. Wang YK, Gao CF, Yun T, Chen Z, Zhang XW, Lv XX, Meng NL, Zhao WZ. Assessment of ERB2 and EGFR gene amplification and protein expression in gastric carcinoma by immunohistochemistry and fluoresence in situ hybridization. Mol Cytogen 2011; 4:14 doi: 10.1186/1755-8166-4-14. 5. Siddiqui MRS, Abdulaai Y, Ali H, Hasan F. A meta-analysis of outcomes after open and laparoscopic Nissen's fundoplication in the treatment for gastro-oesophageal reflux disease. Eur Surg 2011; 44(3): 138-149. 6. Graphodatsky AS, Trifonov VA, Stanyon R. The genome diversity and karyotype evolution of mammals. Mol Cytogen 2011; 4:22 doi: 10.1186/1755-8166-4-22. 7. Maric I,Viaggi S, Caria P, Frau DV, Degan P, Vanni R. Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations. Mol Cytogen 2011; 4: 26 doi: 10.1186/1755-8166-4-26.

Ashraf, M. O. and V. G. Devadoss (2013). "Systematic review and meta-analysis on steroid injection therapy for de Quervain's tenosynovitis in adults." Eur J Orthop Surg Traumatol.

BACKGROUND: de Quervain's tenosynovitis is a painful condition of the wrist which leads to difficulties in performing activities of daily living. AIMS: This systematic review was conducted to examine the effectiveness of steroid injection therapy as compared to splinting for treatment of de Quervain's tenosynovitis in adults. METHODS: The following databases were searched for relevant studies, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO (via NHS Evidence), and Cochrane Library (via Cochrane Collaboration). Synonyms and free texts were used to locate studies. The reference lists of articles were checked for related papers. Hand searching was performed for important relevant journals. All searches found 89 studies, out of which 14 were relevant. Two studies were selected according to the inclusion criteria of the systematic review. Data were extracted and analysed for the two selected randomised trials using a fixed effect model at 95 % confidence intervals. RESULTS: The meta-analysis demonstrated that the total effect estimate was 3 with a narrow 95 % confidence interval (1.89, 4.77). z score for overall effect was 4.66 which was highly significant (p < 0.01). Moderate heterogeneity with I-square test was found to be 64 % but was not significant (p > 0.05). Number needed to treat was 2, which showed that for every two persons treated with steroid injections, one person gets the benefit. CONCLUSION: Steroid injection is an effective form of conservative management for de Quervain's disease although more research is needed to establish the full benefits of the treatment.

Asmussen, S., D. M. Maybauer, et al. (2013). "Extracorporeal membrane oxygenation in burn and smoke inhalation injury." Burns 39(3): 429-35.

A systematic review and meta-analysis was conducted to assess the level of evidence for the use of extracorporeal membrane oxygenation (ECMO) in hypoxemic respiratory failure resulting from burn and smoke inhalation injury. We searched any article published before March 01, 2012. Available studies published in any language were included. Five authors rated each article and assessed the methodological quality of studies using the recommendation of the Oxford Centre for Evidence Based Medicine (OCEBM). Our search yielded 66 total citations but only 29 met the inclusion criteria of burn and/or smoke inhalation injury. There are no available systematic reviews/meta-analyses published that met our inclusion criteria. Only a small number of clinical trials, all with a limited number of patients, were available. The overall data suggests that there is no improvement in survival for burn patients suffering acute hypoxemic respiratory failure, with the use of ECMO. ECMO run times of less than 200h correlate with higher survival compared to 200h or more. Scald burns show a tendency of higher survival than flame burns. In conclusion, the presently available literature is based on insufficient patient numbers; the data obtained and level of evidence generated are limited. The role of ECMO in burn and smoke inhalation injury is therefore unclear. However, ECMO technology and expertise have improved over the last decades. Further research on ECMO in burn and smoke inhalation injury is warranted.

Asmussen, S., D. M. Maybauer, et al. (2013). "A meta-analysis of analgesic and sedative effects of dexmedetomidine in burn patients." Burns.

Sedation for burn patients is provided by a variety of techniques determined usually by institutional preferences. The available pool of drugs has recently expanded to include dexmedetomidine (DEX), a alpha2-adrenergic receptor agonist with analgesic and sedative potential. Beneficial effects of DEX in burn patients have been described in many studies published over the last 5 years. The aim of this study is to perform a systematic review and meta-analysis of the available literature to determine the role of DEX for analgosedation of burn patients. We searched any article that matched the keywords "dexmedetomidine" and "burn", published before October 01, 2012. The methodological quality of studies was assessed using the recommendation of the Oxford Centre for Evidence Based Medicine (OCEBM). Our search yielded eleven total citations, of which four studies (266 patients) met the inclusion criteria of DEX for analgosedation in burn patients. There are no meta-analyses published that met our inclusion criteria. Even though there were only a small number of clinical trials available, the meta-analysis shows evidence for deeper and better sedation as well as for prevention of hypertension when using DEX as an adjunct during burn procedures. No evidence was found for reduced pain scores in this setting. The authors recommend the development of a prospective, randomized, controlled multicenter trial with an adequate number of patients to further elucidate the potentially beneficial effects of DEX for the management of burn patients.

Athe, R., M. V. Vardhana Rao, et al. (2013). "Impact of iron-fortified foods on Hb concentration in children (<10 years): a systematic review and meta-analysis of randomized controlled trials." Public Health Nutr: 1-8.

OBJECTIVE: To combine evidence from randomized controlled trials to assess the effect of Fe-fortified foods on mean Hb concentration in children (<10 years). DESIGN: We conducted a meta-analysis of randomized, controlled, Fe-fortified feeding trials that evaluated Hb concentration. The weighted mean difference was calculated for net changes in Hb by using random-effects models. Meta-regression and covariate analyses were performed to explore the influence of confounders on the net pooled effect. SETTING: Trials were identified through a systematic search of PubMed, the Cochrane Library and secondary references. SUBJECTS: Eighteen studies covering 5142 participants were identified. The duration of feeding of fortified foods ranged from 6 to 12 months in these studies. RESULTS: Eighteen studies were included and evaluated in the meta-analysis. The overall pooled estimate of Hb concentration showed a significant increase in the fortification group compared with the control group (weighted mean difference = 5.09 g/l; 95 % CI 3.23, 6.95 g/l; I 2 = 90 %, tau 2 = 18.37, P < 0.0001). Meta-regression analysis indicated that duration of feeding was positively related to the effect size (regression coefficient = 0.368; 95 % CI 0.005, 0.731; P < 0.05). The net pooled effect size after removing the confounders was 4.74 (95 % CI 3.08, 6.40) g/l. CONCLUSIONS: We observed an association between intake of Fe-fortified foods and Hb concentration in children aged <10 years. Fe-fortified foods could be an effective strategy for reducing Fe-deficiency anaemia in children.

Atlantis, E., P. Fahey, et al. (2013). "Bidirectional associations between clinically relevant depression or anxiety and chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis." Chest.

ABSTRACT BACKGROUND: The longitudinal associations between depression or anxiety and COPD, and their comorbid effect on prognosis have not been adequately addressed by previous reviews. We aimed to systematically assess these associations to inform guidelines and practice. METHOD: We searched electronic databases for articles published before May 2012. Longitudinal studies in adult populations that reported an association between clinically relevant depression or anxiety and COPD, or reported their comorbid effect on exacerbation and/or mortality, were eligible. Risk Ratios (RR) were pooled across studies using random effects models and verified using fixed effects models. Heterogeneity was explored with subgroup and meta-regression analyses. RESULTS: Twenty-two citations yielded 16 studies on depression or anxiety as predictors of COPD outcomes (incident COPD/chronic lung disease or exacerbation) and/or mortality, in 28759 participants followed for 1-8 years, and six studies on COPD as a predictor of depression in 7439159 participants followed for 1-35 years. Depression or anxiety consistently increased the risk of COPD outcomes (RR 1.43[1.22,1.68]), particularly in higher quality studies and people aged </=66 years. Comorbid depression increased the risk of mortality (RR 1.83[1.00,3.36]), particularly in men. Anxiety (or psychological distress) increased the risk of COPD outcomes/mortality in most studies (RR 1.27[1.02,1.58]). Finally, COPD consistently increased the risk of depression (RR 1.69[1.45,1.96]). CONCLUSIONS: Depression and anxiety adversely affect prognosis in COPD, conferring an increased risk of exacerbation and possibly death. Conversely, COPD increases the risk of developing depression. These bidirectional associations suggest potential utility of screening for these disease combinations to direct timely therapeutic intervention.

Augedal, A. W., K. S. Hansen, et al. (2013). "Randomized controlled trials of psychological and pharmacological treatments for nightmares: A meta-analysis." Sleep Med Rev 17(2): 143-52.

A meta-analysis of treatments for nightmares is reported. The studies were identified by database searches and by an inspection of relevant reference lists. The inclusion criteria were: nightmares as a target problem, studies published in English, use of a randomized controlled trials and reporting of nightmare-relevant outcomes. A total of 19 studies, published between 1978 and 2012 were identified, which included 1285 participants. Effect sizes were calculated as Cohen's d. A statistically significant improvement for all studies combined (d = 0.47, 95% CI = 0.33-0.60, fixed effects model; d = 0.49, 95% CI = 0.32-0.66, random effects model) and for psychological treatments alone (d = 0.48, 95% CI = 0.36-0.60, random) and for prazosin alone (d = 0.50, 95% CI = 0.03-0.96, random) was found. Individual therapy format yielded a higher effect size than a self-help format (p = 0.03). Minimal interventions (relaxation, recording) yielded lower overall effect size than studies offering more extensive interventions (p = 0.02). It is concluded that there are both psychological and pharmacological interventions which have documented effects for the treatment of nightmares.

Aune, D., D. S. Chan, et al. (2013). "Red and processed meat intake and risk of colorectal adenomas: a systematic review and meta-analysis of epidemiological studies." Cancer Causes Control.

BACKGROUND: Current evidence indicates that red and processed meat intake increases the risk of colorectal cancer; however, the association with colorectal adenomas is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of epidemiological studies of red and processed meat intake and risk of colorectal adenomas as part of the Continuous Update Project of the World Cancer Research Fund. DESIGN: PubMed and several other databases were searched for relevant studies from their inception up to 31 December 2011. Summary relative risks (RRs) were estimated using a random effects model. RESULTS: Nineteen case-control studies and seven prospective studies were included in the analyses. The summary RR per 100 g/day of red meat was 1.27 (95 % CI 1.16-1.40, I (2) = 5 %, n = 16) for all studies combined, 1.20 (95 % CI 1.06-1.36, I (2) = 0 %, n = 6) for prospective studies, and 1.34 (95 % CI 1.12-1.59, I (2) = 31 %, n = 10) for case-control studies. The summary RR per 50 g/day of processed meat intake was 1.29 (95 % CI 1.10-1.53, I (2) = 27 %, n = 10) for all studies combined, 1.45 (95 % CI 1.10-1.90, I (2) = 0 %, n = 2) for prospective studies, and 1.23 (95 % CI 0.99-1.52, I (2) = 37 %, n = 8) for case-control studies. There was evidence of a nonlinear association between red meat (p (nonlinearity) < 0.001) and processed meat (p (nonlinearity) = 0.01) intake and colorectal adenoma risk. CONCLUSION: These results indicate an elevated risk of colorectal adenomas with intake of red and processed meat, but further prospective studies are warranted.

Autier, P., A. Koechlin, et al. (2013). "Serum insulin and C-peptide concentration and breast cancer: a meta-analysis." Cancer Causes Control.

PURPOSE: Chronic hyperinsulinemia may play a role in breast cancer etiology. We performed a meta-analysis examining whether serum concentrations of insulin and C-peptide are associated with increased breast cancer risk. METHODS: We restricted our analyses to prospective studies. After a systematic literature search, we computed summary relative risks (SRRs) and 95 % confidence intervals (95 % CIs) using random effect models applied to the relative risk associated with the highest versus lowest quantile of serum concentrations. We also graphically examined results in order to identify whether dose-response relationships were present. RESULTS: Six articles including 1,890 cases were retrieved for serum insulin levels and five for serum C-peptide levels including 1,759 cases. SRR and 95 % CI were 1.08 (0.66-1.78) for insulin and 1.04 (0.77-1.41) for C-peptide. Heterogeneity of results between studies was high for insulin and inexistent for C-peptide. Restricting the analysis to women diagnosed with breast cancer before or after menopause did not alter results. In insulin studies, SRR computed from relative risks not adjusted for body mass index (and other risk factors) was 1.22 (0.91-1.63). The SRR fell to 1.02 (0.53-1.97) in studies that adjusted for body mass index and other factors. Similar drops occurred in C-peptide studies, from 1.11 (0.87-1.41) to 1.06 (0.70-1.61). No consistent dose-response relationship was apparent in either pre- or post-menopausal cancers. CONCLUSIONS: Our meta-analysis of observational studies found no evidence of an association between serum insulin or C-peptide concentrations and breast cancer risk. Increased risk found by some studies may have been due to inadequate control for adiposity.

Autorino, R., J. H. Kaouk, et al. (2013). "Current status and future directions of robotic single-site surgery: a systematic review." Eur Urol 63(2): 266-80.

CONTEXT: Despite the increasing interest in laparoendoscopic single-site surgery (LESS) worldwide, the actual role of this novel approach in the field of minimally invasive urologic surgery remains to be determined. It has been postulated that robotic technology could be applied to LESS to overcome the current constraints. OBJECTIVE: To summarize and critically analyze the available evidence on the current status and future of robotic applications in single-site surgery. EVIDENCE ACQUISITION: A systematic literature review was performed in April 2011 using PubMed and the Thomson-Reuters Web of Science. In the free-text protocol, the following terms were applied: robotic single site surgery, robotic single port surgery, robotic single incision surgery, and robotic laparoendoscopic single site surgery. Review articles, editorials, commentaries, and letters to the editor were included only if deemed to contain relevant information. In addition, cited references from the selected articles and from review articles retrieved in the search were assessed for significant manuscripts not previously included. The authors selected 55 articles according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. EVIDENCE SYNTHESIS: The volume of available clinical outcomes of robotic LESS (R-LESS) has considerably grown since the pioneering description of the first successful clinical series of single-port robotic procedures. So far, a cumulative number of roughly 150 robotic urologic LESS cases have been reported by different institutions across the globe with a variety of techniques and port configurations. The feasibility of robot-assisted single-incision colorectal procedures, as well as of many gynecologic procedures, has also been demonstrated. A novel set of single-site instruments specifically dedicated to LESS is now commercially available for use with the da Vinci Si surgical system, and both experimental and clinical use have been reported. However, the current robotic systems were specifically designed for LESS. The ideal robotic platform should have a low external profile, the possibility of being deployed through a single access site, and the possibility of restoring intra-abdominal triangulation while maintaining the maximum degree of freedom for precise maneuvers and strength for reliable traction. Several purpose-built robotic prototypes for single-port surgery are being tested. CONCLUSIONS: Significant advances have been achieved in the field of R-LESS since the first reported clinical series in 2009. Given the several advantages offered by current the da Vinci system, it is likely that its adoption in this field will increase. The recent introduction of purpose-built instrumentation is likely to further foster the application of robotics to LESS. However, we are still far from the ideal robotic platform. Significant improvements are needed before this technique might reach widespread adoption beyond selected centers. Further advances in the field of robotic technology are expected to provide the optimal interface to facilitate LESS.

Avery, C. L., C. M. Sitlani, et al. (2013). "Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval." Pharmacogenomics J.

Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 x 10-8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.The Pharmacogenomics Journal advance online publication, 5 March 2013; doi:10.1038/tpj.2013.4.

Awad, S., K. K. Varadhan, et al. (2013). "A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery." Clin Nutr 32(1): 34-44.

BACKGROUND & AIMS: Whilst preoperative carbohydrate treatment (PCT) results in beneficial physiological effects, the effects on postoperative clinical outcomes remain unclear and were studied in this meta-analysis. METHODS: Prospective studies that randomised adult non-diabetic patients to either PCT (>/=50 g oral carbohydrates 2-4 h pre-anaesthesia) or control (fasted/placebo) were included. The primary outcome was length of hospital stay. Secondary outcomes included development of postoperative insulin resistance, complications, nausea and vomiting. Methodological quality was assessed using GRADEpro((R)) software. RESULTS: Twenty-one randomised studies of 1685 patients (733 PCT: 952 control) were included. No overall difference in length of stay was noted for analysis of all studies or subgroups of patients undergoing surgery with an expected hospital stay </=2 days or orthopaedic procedures. However, patients undergoing major abdominal surgery following PCT had reduced length of stay [mean difference, 95% confidence interval: -1.08 (-1.87 to -0.29); I(2) = 60%, p = 0.007]. PCT reduced postoperative insulin resistance with no effects on in-hospital complications over control (risk ratio, 95% confidence interval, 0.88 (0.50-1.53), I(2) = 41%; p = 0.640). There was significant heterogeneity amongst studies and, therefore, quality of evidence was low to moderate. CONCLUSIONS: PCT may be associated with reduced length of stay in patients undergoing major abdominal surgery, however, the included studies were of low to moderate quality.

Awe, J. P., A. Vega Crespo, et al. (2013). "BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells." Stem Cell Res Ther 4(1): 15.

ABSTRACT: INTRODUCTION: The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through a NF-kappaB-inhibition based mechanism, could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. METHODS: We tested various chemical and molecular small molecules on their ability to suppress the innate immune response seen upon synthetic mRNA transfection. Three molecules-B18R, BX795, and BAY11- were used in immunocytochemical and proliferation based assays. We also utilized global transcriptional meta-analysis coupled with quantitative PCR to identify relative gene expression downstream of OCT4. RESULTS: We found that human skin cells cultured in the presence of BAY11 resulted in reproducible increased expression of OCT4 that did not inhibit normal cell proliferation. The increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G, suggesting the expressed OCT4 was functional. We also discovered a novel OCT4 putative downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. CONCLUSIONS: For the first time we have shown that small molecule-based stabilization of synthetic mRNA expression can be achieved with use of BAY11. This small molecule based inhibition of innate immune responses and subsequent robust expression of transfected synthetic mRNAs may have multiple applications for future cell-based research and therapeutics.

Aya, H. D., M. Cecconi, et al. (2013). "Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis." Br J Anaesth.

BACKGROUND: /st>Perioperative mortality after cardiac surgery has decreased in recent years although postoperative morbidity is still significant. Although there is evidence that perioperative goal-directed haemodynamic therapy (GDT) may reduce surgical mortality and morbidity in non-cardiac surgical patients, the data are less clear after cardiac surgery. The objective of this review is to perform a meta-analysis on the effects of perioperative GDT on mortality, morbidity, and length of hospital stay in cardiac surgical patients. METHODS: /st>We conducted a systematic review using Medline, EMBASE, and the Cochrane Controlled Clinical Trials Register. Additional sources were sought from experts. The inclusion criteria were randomized controlled trials, mortality reported as an outcome, pre-emptive haemodynamic intervention, and cardiac surgical population. Included studies were examined in full and subjected to quantifiable analysis, subgroup analysis, and sensitivity analysis where possible. Data synthesis was obtained by using odds ratio (OR) and mean difference (MD) for continuous data with 95% confidence interval (CI) utilizing a random-effects model. RESULTS: /st>From 4986 potential studies, 5 met all the inclusion criteria (699 patients). The quantitative analysis showed that the use of GDT reduced the postoperative complication rate (OR 0.33, 95% CI 0.15-0.73; P=0,006) and hospital length of stay (MD -2.44, 95% CI -4.03 to -0.84; P=0,003). There was no significant reduction in mortality. CONCLUSION: /st>The use of pre-emptive GDT in cardiac surgery reduces morbidity and hospital length of stay.

Aydiner, A. (2013). "Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women." Breast.

The present meta-analysis examines randomized trials of third-generation aromatase inhibitors (AIs) as alternatives to tamoxifen in three treatment settings: monotherapy, sequenced therapy and extended therapy. Eleven randomized controlled trials (RCTs) were chosen based on their similarity in terms of study design and included 34,070 post-menopausal women who had undergone surgery for estrogen-sensitive early breast cancer. DFS was significantly improved by AI monotherapy (Hazard Ratio (HR): 0.89, p = 0.001), sequenced therapy (HR: 0.7, p < 0.00001) and extended therapy (HR: 0.62, p < 0.00001). All of the patients benefited significantly from sequenced therapy (HR: 0.81, p = 0.003), and hormone receptor-positive patients benefited from AI monotherapy (HR = 0.92, p = 0.046) with respect to OS. AI monotherapy conferred significantly lower risks for thromboembolic events (OR = 0.61; p < 0.001) and endometrial cancer (OR = 0.26; p < 0.001) compared with tamoxifen monotherapy; however, there was a greater risk of cardiovascular events (OR = 1.20; p = 0.030). Sequenced therapy was also superior in terms of endometrial cancer but was inferior with respect to fractures, thromboembolic and cardiovascular events.

Ayerbe, L., S. Ayis, et al. (2013). "Natural history, predictors and outcomes of depression after stroke: systematic review and meta-analysis." Br J Psychiatry 202(1): 14-21.

BACKGROUND: Depression after stroke is a distressing problem that may be associated with other negative health outcomes. AIMS: To estimate the natural history, predictors and outcomes of depression after stroke. METHOD: Studies published up to 31 August 2011 were searched and reviewed according to accepted criteria. RESULTS: Out of 13 558 references initially found, 50 studies were included. Prevalence of depression was 29% (95% CI 25-32), and remains stable up to 10 years after stroke, with a cumulative incidence of 39-52% within 5 years of stroke. The rate of recovery from depression among patients depressed a few months after stroke ranged from 15 to 57% 1 year after stroke. Major predictors of depression are disability, depression pre-stroke, cognitive impairment, stroke severity and anxiety. Lower quality of life, mortality and disability are independent outcomes of depression after stroke. CONCLUSION: Interventions for depression and its potential outcomes are required.

Baandrup, L., M. T. Faber, et al. (2013). "Nonsteroidal anti-inflammatory drugs and risk of ovarian cancer: systematic review and meta-analysis of observational studies." Acta Obstet Gynecol Scand 92(3): 245-55.

OBJECTIVE: Several observational studies have investigated the association between nonsteroidal anti-inflammatory drug (NSAID) use and ovarian cancer risk, but with conflicting results. We performed a systematic review and meta-analysis of the association between NSAID use and ovarian cancer risk. DESIGN: Systematic review and meta-analysis of observational studies published until September 2012. SETTING: Studies were identified from the PubMed database. POPULATION: Fourteen case-control and seven cohort studies were included. METHODS: Pooled relative risks (RRs) with corresponding 95% confidence intervals (CI) for aspirin and non-aspirin NSAIDs, separately, were calculated. Both fixed and random effect models were applied, but only random effect pooled RRs are presented. Risk estimates for invasive and borderline ovarian tumors combined and for invasive ovarian tumors only were calculated. Furthermore, heterogeneity and publication bias were evaluated. MAIN OUTCOME MEASURES: Ovarian cancer. RESULTS: In the combined analysis, a slight inverse association between use of aspirin (RR 0.93; 95% CI 0.84-1.02) and non-aspirin NSAIDs (RR 0.94; 95% CI 0.84-1.06) and ovarian cancer risk was found, although it was not statistically significant. However, the risk of invasive ovarian cancer was significantly reduced with use of aspirin (RR 0.88; 95% CI 0.79-0.98). A similar tendency was observed for non-aspirin NSAIDs, but the results were not significant. CONCLUSIONS: This meta-analysis showed a slight inverse association between NSAIDs and risk of ovarian cancer. However, data suggest that a chemopreventive effect of NSAIDs may be restricted to invasive ovarian tumors. Further research on NSAIDs and ovarian cancer is needed before definite conclusions can be drawn.

Baardseth, T. P., S. B. Goldberg, et al. (2013). "Cognitive-behavioral therapy versus other therapies: Redux." Clin Psychol Rev 33(3): 395-405.

Despite the evidence suggesting that all treatments intended to be therapeutic are equally efficacious, the conjecture that one form of treatment, namely cognitive-behavioral therapy (CBT), is superior to all other treatment persists. The purpose of the current study was to (a) reanalyze the clinical trials from an earlier meta-analysis that compared CBT to 'other therapies' for depression and anxiety (viz., Tolin, 2010) and (b) conduct a methodologically rigorous and comprehensive meta-analysis to determine the relative efficacy of CBT and bona fide non-CBT treatments for adult anxiety disorders. Although the reanalysis was consistent with the earlier meta-analysis' findings of small to medium effect sizes for disorder-specific symptom measures, the reanalysis revealed no evidence for the superiority of CBT for depression and anxiety for outcomes that were not disorder-specific. Following the reanalysis, a comprehensive anxiety meta-analysis that utilized a survey of 91 CBT experts from the Association of Behavioral and Cognitive Therapists (ABCT) to consensually identify CBT treatments was conducted. Thirteen clinical trials met the inclusion criteria. There were no differences between CBT treatments and bona fide non-CBT treatments across disorder-specific and non-disorder specific symptom measures. These analyses, in combination with previous meta-analytic findings, fail to provide corroborative evidence for the conjecture that CBT is superior to bona fide non-CBT treatments.

Babatunde, O. O. and J. J. Forsyth (2013). "Quantitative Ultrasound and bone's response to exercise: a meta analysis." Bone 53(1): 311-8.

The utility of Quantitative Ultrasound (QUS) for assessing and monitoring changes in bone health due to exercise is limited for lack of adequate research evidence. Restrictions to bone density testing and the enduring debate over repeat dual energy absorptiometry testing spells uncertainty over clinical and non-clinical evaluation of exercise for prevention of osteoporosis. This study, via systematic review and meta-analysis, aimed to paint a portrait of current evidence regarding QUS' application to monitoring bone's adaptive response to exercise interventions. METHODS: Structured and comprehensive search of databases was undertaken along with hand-searching of key journals and reference lists to locate relevant studies published up to December 2011. Twelve articles met predetermined inclusion criteria. The effect of exercise interventions for improving bone health, as measured by QUS of the calcaneum, was examined across the age spectrum. Study outcomes for analysis: absolute (dB/MHz) or relative change (%) in broadband ultrasound attenuation (BUA) and/or os calcis stiffness index were compared by calculating standardised mean difference (SMD) using fixed- and random-effects models. RESULTS: Quality of included trials varied from low to high on a scale of one to three. Four to 36months of exercise led to a significant improvement in calcaneum BUA (0.98 SMD, 95% CI 0.80, 1.16, overall effect Z-value=10.72, p=0.001) across the age spectrum. CONCLUSION: The meta-analysis attests to the sensitivity of QUS to exercise-induced changes in bone health across the age groups. QUS may be considered for use in exercise-based bone health interventions for preventing osteoporosis.

Babchishin, K. M., K. L. Nunes, et al. (2013). "The Validity of Implicit Association Test (IAT) Measures of Sexual Attraction to Children: A Meta-Analysis." Arch Sex Behav 42(3): 487-99.

The current study presents a quantitative review of the discriminative and convergent validity of Implicit Association Test (IAT) measures adapted to assess sexual interest in children. IAT measures were able to distinguish sex offenders against children (SOC) from non-SOC (M weighted d from random-effects = 0.63, 95 % CI [0.42-0.83], N = 707, k = 12). The largest group differences were found between SOC and non-offenders, followed by non-sex offenders and rapists. IAT measures using sex versus not sex (and similar attribute categories, such as sex vs. neutral) provided superior discrimination compared to IAT measures using sexy versus not sexy (and similar attribute categories, such as erotic vs. non-erotic). The IAT measures had a moderate relationship to self-report (r = .27, 95 % CI [.13-.40], N = 182), sexual offense history variables (r = .27, 95 % CI [.08-.43], N = 145), and viewing time (r = .30, 95 % CI [.16-.43], N = 180) measures of sexual interest in children. Although these IAT measures can discriminate between groups and show convergence with other measures of sexual interest, a better understanding of the construct validity of these tools is required before their use in the assessment, treatment, and supervision of sex offenders.

Bachmann, B., R. S. Taylor, et al. (2013). "The association between corneal neovascularization and visual acuity: a systematic review." Acta Ophthalmol 91(1): 12-9.

PURPOSE: Corneal neovascularization (CNV) is thought to negatively influence visual acuity. New therapeutic options that offer a differentiated influence on the ingrowths or regression of either corneal blood or lymphatic vessels force us to re-evaluate the association between CNV and visual acuity. METHODS: A systematic review was conducted. Electronic databases were searched up to August 2009. Given the heterogeneity in study populations, interventions and measures of association, we were unable to undertake meta-analysis. The association between CNV and visual acuity was reported descriptively for each study. RESULTS: Eleven studies using either vascular endothelial growth factor inhibitor treatments (i.e. bevacizumab, Avastin((R)) ; Hoffmann-La Roche AG, Basel, Switzerland) or an antiangiogenic treatment based on IRS-1 modulation [Gene-Signal (GS) 101, Aganirsen((R)) ; GeneSignal, Evry (Paris), France] in a total of 131 patients (142 eyes) with corneal neovascularization were included. Ten of the eleven studies reported evidence of a statistically significant reduction in neovascularization following treatment. However, only four studies reported a statistically significant improvement in visual acuity following therapy. We found no studies that assessed the patient-level association between the change in neovascularization and visual acuity. CONCLUSION: This systematic review found that there is currently weak evidence to support the hypothesis that in patients with pathological neovascularization, a treatment-related reduction in neovascularization is associated with an increase in visual acuity. There is a need for future appropriately designed studies.

Bae, J. M., Y. Y. Choi, et al. (2013). "Mohs micrographic surgery for extramammary Paget disease: A pooled analysis of individual patient data." J Am Acad Dermatol.

BACKGROUND: Extramammary Paget disease (EMPD) is a rare intraepithelial neoplasm of the skin characterized by ill-defined margins and high recurrence rates after wide local excision. Although Mohs micrographic surgery (MMS) has been proposed to decrease the rate of local recurrence, the efficacy of MMS for this condition has not yet been established. OBJECTIVE: We sought to assess the efficacy of MMS for the treatment of EMPD. METHODS: A comprehensive systematic review and individual patient data meta-analysis was performed including all available clinical studies and case reports with 5 or more subjects describing the use of MMS for EMPD. RESULTS: Eight studies were identified and included in the current review: 3 retrospective studies and 5 case series. In all, 81 patients with 90 cases of MMS were included from these 8 studies. The overall recurrence rate for EMPD after MMS was 12.2% correlating with an estimated 5-year tumor-free rate of 83.6% by using Kaplan-Meier curve analysis. The treatment of EMPD with MMS resulted in significantly lower recurrence rates than wide local excision in this meta-analysis of 3 observational studies with comparators (odds ratio 0.20; 95% confidence interval 0.05-0.81). LIMITATIONS: Limitations include lack of controlled trials, small sample sizes in the included studies, and publication bias. CONCLUSION: The current evidence supports the efficacy of MMS in the treatment of EMPD. Further controlled clinical trials are needed.

Baggaley, R. F., R. G. White, et al. (2013). "Heterosexual HIV-1 infectiousness and antiretroviral use: systematic review of prospective studies of discordant couples." Epidemiology 24(1): 110-21.

BACKGROUND: Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. METHODS: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. RESULTS: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). CONCLUSIONS: ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms.

Bagnardi, V., M. Rota, et al. (2013). "Light alcohol drinking and cancer: a meta-analysis." Ann Oncol 24(2): 301-8.

BACKGROUND: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). PATIENTS AND METHODS: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. RESULTS: We included 222 articles comprising approximately 92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that approximately 5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. CONCLUSIONS: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

Bai, H., Y. Li, et al. (2013). "Effectiveness of Chinese Herbal Medicine as an Adjunctive Treatment for Dilated Cardiomyopathy in Patients with Heart Failure." J Altern Complement Med.

Abstract Objectives: To evaluate the effectiveness and safety of Chinese herbal medicine (CHM) as an adjunctive treatment for patients with dilated cardiomyopathy (DCM) and heart failure. Design: Studies on biomedical treatment plus CHM versus biomedical treatment alone in treating patients with DCM and heart failure were retrieved from PubMed and other major databases (1980-2011). Meta-analysis was performed on the overall effects on effective rate, left ventricular ejection fraction, left ventricular diastolic end diameter, and other outcome measures. Results: Twenty-seven studies with 1887 patients were included. Compared with biomedical treatment alone, biomedical treatment plus CHM showed significant improvement in effective rate (relative risk, 1.26; 95% confidence interval [CI], 1.19-1.34), left ventricular ejection fraction (%) (mean difference, 5.88; 95% CI, 3.92-7.85), left ventricular diastolic end diameter (mm) (mean difference, -2.78; 95% CI, -5.15 to -0.42), and other outcome measures. Most adverse events observed in the studies were not severe and resolved without special treatment. Conclusions: This meta-analysis indicated that biomedical treatment plus CHM is more effective than biomedical treatment alone in treating patients with DCM and heart failure. However, further studies with long-term follow-up, systemic adverse events evaluation, and other ethnic groups are still required to verify the efficacy and safety of CHM as an adjunctive treatment in all patients with DCM and heart failure.

Bai, M., Z. Yang, et al. (2013). "L-ornithine-L-aspartate for Hepatic Encephalopathy in Patients with Cirrhosis: A Meta-analysis of Randomized Controlled Trials." J Gastroenterol Hepatol.

BACKGROUND AND AIM: Several randomized, controlled trials that evaluated the effectiveness of L-ornithine-L-aspartate (LOLA) in the treatment of hepatic encephalopathy (HE) have been published recently. Our purpose was to update the meta-analysis to reevaluate the safety and efficacy of LOLA on HE in patients with cirrhosis. METHODS: The following databases were searched from inception to June 2012: Medline, Embase, and the Cochrane Central Register of Controlled Trials (Issue 6). Differences between groups were assessed by the pooled risk ratio (RR) or mean difference (MD). Possible sources of heterogeneity were assessed by sensitivity analyses. RESULTS: Eight randomized controlled trials with 646 patients were included. When comparing placebo/no-intervention control, LOLA was significantly more effective in the improvement of HE in the total (RR: 1.49, 95% CI: 1.10 to 2.01), overt HE (RR: 1.33, 95% CI: 1.04 to 1.69), and minimal HE patients (RR: 2.25, 95% CI: 1.33 to 3.82). Furthermore, the reduction of fasting ammonia significantly favored LOLA (post-treatment value, MD: -18.26, 95% CI: -26.96 to -9.56; change, MD: 8.59, 95% CI: 5.22 to 11.96). The tolerance ratio, incidence of adverse events, and mortality were not significantly different between LOLA and the placebo/no-intervention control. LOLA and lactulose demonstrated similar effectiveness in the improvement of HE (RR: 0.88, 95% CI: 0.57 to 1.35). CONCLUSIONS: LOLA benefits both overt and minimal HE patients in the improvement of HE by reducing the serum ammonia concentration compared to the placebo/no-intervention control. Further, evaluations between LOLA and other effective treatments are needed.

Baker, N. J., B. A. Bancroft, et al. (2013). "A meta-analysis of the effects of pesticides and fertilizers on survival and growth of amphibians." Sci Total Environ 449C: 150-156.

The input of agrochemicals has contributed to alteration of community composition in managed and associated natural systems, including amphibian biodiversity. Pesticides and fertilizers negatively affect many amphibian species and can cause mortality and sublethal effects, such as reduced growth and increased susceptibility to disease. However, the effect of pesticides and fertilizers varies among amphibian species. We used meta-analytic techniques to quantify the lethal and sublethal effects of pesticides and fertilizers on amphibians in an effort to review the published work to date and produce generalized conclusions. We found that pesticides and fertilizers had a negative effect on survival of -0.9027 and growth of -0.0737 across all reported amphibian species. We also observed differences between chemical classes in their impact on amphibians: inorganic fertilizers, organophosphates, chloropyridinyl, phosphonoglycines, carbamates, and triazines negatively affected amphibian survival, while organophosphates and phosphonoglycines negatively affected amphibian growth. Our results suggest that pesticides and fertilizers are an important stressor for amphibians in agriculturally dominated systems. Furthermore, certain chemical classes are more likely to harm amphibians. Best management practices in agroecosystems should incorporate amphibian species-specific response to agrochemicals as well as life stage dependent susceptibility to best conserve amphibian biodiversity in these landscapes.

Balevi, B. (2013). "In selected sites, short, rough-surfaced dental implants are as successful as long dental implants: a critical summary of Pommer B, Frantal S, Willer J, Posch M, Watzek G, Tepper G. Impact of dental implant length on early failure rates: a meta-analysis of observational studies. J Clin Periodontol 2011;38(9):856-863." J Am Dent Assoc 144(2): 195-6.

CLINICAL QUESTION: In adult patients, do short dental implants (< 10 millimeters) lead to failure rates similar to those for longer implants (>/= 10 mm) in the first year of loading? REVIEW METHODS: Two independent reviewers searched three electronic databases and 29 journals for articles published from January 1998 to January 2008. The authors included in the review only English-language, prospective observational studies in which the allocation decision occurred in the course of usual treatment. Also, implants must have been placed in nonaugmented healed jawbone after a conventional healing period of three to six months. The primary outcome measured was implant failure within the first year of prosthetic loading, determined on the basis of established criteria.1 A meta-analysis was carried out in which the authors compared the association between implant length and failure. In addition, the authors performed subgroup analyses of failure as a function of the implants' diameter, surface texture and location in the maxillary or mandibular arch. MAIN RESULTS: Fifty-four trials, including 19,563 dental implants (with only a 2.4 percent dropout rate), met the inclusion criteria. The results of the meta-analysis, which consisted of 40 studies (2,223 short implants and 14,158 long implants), showed that shorter implants had an overall failure rate statistically significantly higher than that for long implants within the first year of loading (odds ratio [OR] = 1.8; 95 percent confidence interval [CI], 1.3-2.5). The results of subgroup analyses showed a statistically significant difference in failure rates for short and long implants in the maxilla, but no difference in the mandible. However, with the possible exception of the anterior maxilla, the failure rates for rough surfaced implants in the two groups (1,298 short implants and 7,544 long implants) were not statistically significantly different (OR = 1.1; 95 percent CI, 0.6-2.1). The authors found no association between implant diameter and failure rates within one year of prosthetic loading. CONCLUSIONS: With the possible exception of the maxillary anterior area, rough-surfaced short implants with a minimum length of 7 mm present no additional risk of failure within the first year of loading.

Balottin, U., P. F. Poli, et al. (2013). "Psychopathological symptoms in child and adolescent migraine and tension-type headache: a meta-analysis." Cephalalgia 33(2): 112-22.

INTRODUCTION: After decades of research, the importance of psychological factors in child and adolescent headache is no longer in doubt. However, it is not clearly understood whether different types of headache are comorbid with specific kinds of psychopathology. To address this issue, we set out to establish whether young patients with migraine do or do not show significant levels of psychopathological symptoms compared with age-matched healthy controls and patients with tension-type headache (TTH). METHODS: Ten studies were selected on the basis of a widely used psychodiagnostic tool (the Child Behavior Checklist (CBCL)) and by applying rigorous criteria: The studies were compared in a meta-analysis in order to evaluate the presence of Internalizing (mainly anxiety and depression) and Externalizing (mainly behavioral problems) symptoms in different types of headache (and versus healthy controls). FINDINGS: Patients with migraine showed more psychopathological symptoms than healthy controls. TTH patients also had more psychopathology than controls, although the difference was more marked in the area of Internalizing disorders. Finally, no differences emerged between migraine and TTH. DISCUSSION AND CONCLUSION: Psychopathological symptoms affect children with migraine, but also children with TTH. Biological, pathophysiological and clinical links need to be established. Effective treatment of affected children and adolescents is imperative in order to prevent chronic evolution. In this context, the CBCL may be a good screening instrument with a view to developing a tailored clinical approach.

Baltzer, P. A. and M. Dietzel (2013). "Breast Lesions: Diagnosis by Using Proton MR Spectroscopy at 1.5 and 3.0 T--Systematic Review and Meta-Analysis." Radiology.

Purpose:To perform a systematic review and meta-analysis to estimate the diagnostic performance of breast proton magnetic resonance (MR) spectroscopy in differentiating benign from malignant lesions and to identify variables that influence the accuracy of MR spectroscopy.Materials and Methods:A comprehensive search of the PubMed database was performed on articles listed until January 6, 2012. The Medical Subject Headings and text words for the terms "breast," "spectroscopy," and "magnetic resonance" were used. Investigations including more than 10 patients at 1.5 T or 3.0 T applying one-dimensional single-voxel MR spectroscopy or spatially resolved MR spectroscopy for differentiation between benign and malignant breast lesions were eligible. A reference standard had to be established either by means of histopathologic examination or imaging follow-up of 12 or more months. Statistical analysis included pooling of diagnostic accuracy, control for data inhomogeneity, and identification of publication bias.Results:Nineteen studies were used for general data pooling. The studies included a total of 1183 patients and 1198 lesions (773 malignant, 452 benign). Pooled sensitivity and specificity were 73% (556 of 761; 95% confidence interval [CI]: 64%, 82%) and 88% (386 of 439; 95% CI: 85%, 91%), respectively. The pooled diagnostic odds ratio (DOR) was 34.30 (95% CI: 16.71, 70.43). For breast cancers versus benign lesions, the area under the symmetric summary receiver operating characteristic curve of MR spectroscopy was 0.88, and the Q* index was 0.81. There was evidence of between-studies heterogeneity regarding sensitivity and DOR (P < .0001). No significant influences of higher field strength, postcontrast acquisition, or qualitative versus quantitative MR spectroscopy measurements were identified. Egger testing confirmed significant publication bias in studies including small numbers of patients (P < .0001).Conclusion:Breast MR spectroscopy shows variable sensitivity and high specificity in the diagnosis of breast lesions, independent from the technical MR spectroscopy approach. Because of significant publication bias, pooled diagnostic measures might be overestimated.(c) RSNA, 2013.

Bangalore, S., S. Pursnani, et al. (2013). "Percutaneous coronary intervention versus optimal medical therapy for prevention of spontaneous myocardial infarction in subjects with stable ischemic heart disease." Circulation 127(7): 769-81.

BACKGROUND: Contemporary studies have shown that spontaneous but not procedural myocardial infarction (MI) is related to subsequent mortality. Whether percutaneous coronary intervention (PCI) reduces spontaneous (nonprocedural) MI is unknown. METHODS AND RESULTS: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials until October 2012 comparing PCI with optimal medical therapy (OMT) for stable ischemic heart disease and reporting MI outcomes: spontaneous nonprocedural MI, procedural MI, and all MI, including procedure-related MI. Given the varying length of follow-up between trials, a mixed-effect Poisson regression meta-analysis was used. From 12 randomized clinical trials with 37 548 patient-years of follow-up, PCI compared with OMT alone was associated with a significantly lower incident rate ratio (IRR) for spontaneous nonprocedural MI (IRR=0.76; 95% confidence interval [CI], 0.58-0.99) at the risk of a higher rate of procedural MI (IRR=4.11; 95% CI, 2.53-6.88) without any difference in the risk of all MI (IRR=0.96; 95% CI, 0.74-1.21). The point estimate for PCI versus OMT for all-cause mortality (IRR=0.88; 95% CI, 0.75-1.03) and cardiovascular mortality (IRR=0.70; 95% CI, 0.44-1.09) paralleled that for spontaneous nonprocedural MI (but not procedural or all nonfatal MI), although these were not statistically significant. CONCLUSIONS: PCI compared with OMT reduced spontaneous MI at the risk of procedural MI without any difference in all MI. Consistent with prior studies showing that spontaneous MI but not procedural MI is related to subsequent mortality, in the present report the point estimate for reduced mortality with PCI compared with OMT paralleled the prevention of spontaneous MI with PCI. Further studies are needed to determine whether these associations are causal.

Bangert, M., P. Ziegenhein, et al. (2013). "Comparison of beam angle selection strategies for intracranial IMRT." Med Phys 40(1): 011716.

Purpose: Various strategies to select beneficial beam ensembles for intensity-modulated radiation therapy (IMRT) have been suggested over the years. These beam angle selection (BAS) strategies are usually evaluated against reference configurations applying equispaced coplanar beams but they are not compared to one another. Here, the authors present a meta analysis of four BAS strategies that incorporates fluence optimization (FO) into BAS by combinatorial optimization (CO) and one BAS strategy that decouples FO from BAS, i.e., spherical cluster analysis (SCA). The underlying parameters of the BAS process are investigated and the dosimetric benefits of the BAS strategies are quantified.Methods: For three intracranial lesions in proximity to organs at risk (OARs) the authors compare treatment plans applying equispaced coplanar beam ensembles with treatment plans using five different BAS strategies, i.e., four CO techniques and SCA, to establish coplanar and noncoplanar beam ensembles. Treatment plans applying 5, 7, 9, and 11 beams are investigated. For the CO strategies the authors perform BAS runs with a 5 degrees , 10 degrees , 15 degrees , and 20 degrees angular resolution, which corresponds to a minimum of 18 coplanar and a maximum of 1400 noncoplanar candidate beams. In total 272 treatment plans with different BAS settings are generated for every patient. The quality of the treatment plans is compared based on the protection of OARs yet integral dose, target homogeneity, and target conformity are also considered.Results: It is possible to reduce the average mean and maximum doses in OARs by more than 4 Gy (1 Gy) with optimized noncoplanar (coplanar) beam ensembles found with BAS by CO or SCA. For BAS including FO by CO, the individual algorithm used and the angular resolution in the space of candidate beams does not have a crucial impact on the quality of the resulting treatment plans. All CO algorithms yield similar target conformity and slightly improved target homogeneity in comparison to equispaced coplanar setups. Furthermore, optimized coplanar (noncoplanar) beam ensembles enabled more than a 6% (5%) reduction of the integral dose. For SCA, however, integral dose was increased and target conformity was decreased in comparison to equispaced coplanar setups-especially for a small number of beams.Conclusion: Both BAS strategies incorporating FO by CO and independent BAS strategies excluding FO provide dose savings in OARs for optimized coplanar and especially noncoplanar beam ensembles; they should not be neglected in the clinic.

Bao, C., X. Yang, et al. (2013). "Diabetes mellitus and incidence and mortality of kidney cancer: A meta-analysis." J Diabetes Complications.

BACKGROUND: Diabetes is associated with increased risk of a spectrum of cancers, but there are few meta-analyses on the association between diabetes and kidney cancer. We performed a meta-analysis of case-control studies and cohort studies to address the incidence and mortality of kidney cancer in diabetes. METHODS: Studies were identified by searching PubMed database and manual assessment of the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effect model. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 24 studies were included. We found that diabetes was significantly associated with increased risk of kidney cancer (RR=1.40, 95% CI=1.16 to 1.69), and the results were consistent between case-control and cohort studies. A slightly stronger positive relation was observed in women (RR=1.47, 95% CI=1.18 to 1.83) than in men (RR=1.28, 95% CI=1.10 to 1.48). Additional analyses indicated that the increased risk of kidney cancer was independent of alcohol consumption, body mass index (BMI)/obesity and smoking. However, there was no association between diabetes and mortality of kidney cancer (RR=1.12, 95% CI=0.99 to 1.20), without heterogeneity (P=0.419, I(2)=1.8%). CONCLUSIONS: Diabetes mellitus may increase the risk of kidney cancer in both women and men.

Bao, Y., E. L. Giovannucci, et al. (2013). "A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts." J Natl Cancer Inst 105(2): 95-103.

BACKGROUND: The adipocyte-secreted hormone adiponectin has insulin-sensitizing and anti-inflammatory properties. Although development of pancreatic cancer is associated with states of insulin resistance and chronic inflammation, the mechanistic basis of the associations is poorly understood. METHODS: To determine whether prediagnostic plasma levels of adiponectin are associated with risk of pancreatic cancer, we conducted a nested case-control study of 468 pancreatic cancer case subjects and 1080 matched control subjects from five prospective US cohorts: Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. Control subjects were matched to case subjects by prospective cohort, year of birth, smoking status, fasting status, and month of blood draw. All samples for plasma adiponectin were handled identically in a single batch. Odds ratios were calculated with conditional logistic regression, and linearity of the association between adiponectin and pancreatic cancer was modeled with restricted cubic spline regression. All statistical tests were two-sided. RESULTS: Median plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 microg/mL, P = .009). Plasma adiponectin was inversely associated with pancreatic cancer risk, which was consistent across the five prospective cohorts (P (heterogeneity) = .49) and independent of other markers of insulin resistance (eg, diabetes, body mass index, physical activity, plasma C-peptide). Compared with the lowest quintile of adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios ([ORs] 95% confidence intervals [CIs]) of OR = 0.61 (95% CI = 0.43 to 0.86), OR = 0.58 (95% CI = 0.41 to 0.84), OR = 0.59 (95% CI = 0.40 to 0.87), and OR = 0.66 (95% CI = 0.44 to 0.97), respectively (P (trend) = .04). Restricted cubic spline regression confirmed a nonlinear association (P (nonlinearity) < .01). The association was not modified by sex, smoking, body mass index, physical activity, or C-peptide (all P (interaction) > .10). CONCLUSIONS: In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.

Bapoje, S. R., A. Bahia, et al. (2013). "The Effects of Mineralocorticoid Receptor Antagonists on the Risk of Sudden Cardiac Death in Patients with Left Ventricular Systolic Dysfunction: A Meta-analysis of Randomized Controlled Trials." Circ Heart Fail.

BACKGROUND: -Sudden cardiac death (SCD) is a leading cause of mortality in patients with left ventricular systolic dysfunction (LVSD). Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. The objective of this meta-analysis was to assess the impact of MRAs on SCD in patients with LVSD. METHODS AND RESULTS: -We systematically searched PubMed, EMBASE, Cochrane and other databases through March 30(th) 2012 without language restrictions. We included trials that enrolled patients with left ventricular ejection fraction of </= 45%, randomized subjects to MRAs vs. control, and reported outcomes on SCD, total and cardiovascular mortality. Eight published trials that enrolled 11,875 patients met inclusion criteria. Of these, six reported data on SCD and cardiovascular mortality, and seven reported data on total mortality. No heterogeneity was observed among the trials. Patients treated with MRAs had 23% lower odds of experiencing SCD compared with controls, OR = 0.77 [95% CI 0.66-0.89; p = 0.001]. Similar reductions were observed in cardiovascular [OR 0.75; 95 % CI 0.68- 0.84; p < 0.001], and total mortality [OR = 0.74; 95% CI 0.63- 0.86; p < 0.001]. Although publication bias was observed, the results did not change after a trim and fill test suggesting that the impact of this bias was likely insignificant. CONCLUSIONS: -MRAs reduce the risk of SCD in patients with LVSD. Comparative effectiveness studies of MRAs on SCD in usual care as well as studies evaluating the efficacy of other therapies to prevent SCD in patients receiving optimal MRA use are needed to guide clinical decision-making.

Baral, S. D., T. Poteat, et al. (2013). "Worldwide burden of HIV in transgender women: a systematic review and meta-analysis." Lancet Infect Dis 13(3): 214-22.

BACKGROUND: Previous systematic reviews have identified a high prevalence of HIV infection in transgender women in the USA and in those who sell sex (compared with both female and male sex workers). However, little is known about the burden of HIV infection in transgender women worldwide. We aimed to better assess the relative HIV burden in all transgender women worldwide. METHODS: We did a systematic review and meta-analysis of studies that assessed HIV infection burdens in transgender women that were published between Jan 1, 2000, and Nov 30, 2011. Meta-analysis was completed with the Mantel-Haenszel method, and random-effects modelling was used to compare HIV burdens in transgender women with that in adults in the countries for which data were available. FINDINGS: Data were only available for countries with male-predominant HIV epidemics, which included the USA, six Asia-Pacific countries, five in Latin America, and three in Europe. The pooled HIV prevalence was 19.1% (95% CI 17.4-20.7) in 11 066 transgender women worldwide. In 7197 transgender women sampled in ten low-income and middle-income countries, HIV prevalence was 17.7% (95% CI 15.6-19.8). In 3869 transgender women sampled in five high-income countries, HIV prevalence was 21.6% (95% CI 18.8-24.3). The odds ratio for being infected with HIV in transgender women compared with all adults of reproductive age across the 15 countries was 48.8 (95% CI 21.2-76.3) and did not differ for those in low-income and middle-income countries compared with those in high-income countries. INTERPRETATION: Our findings suggest that transgender women are a very high burden population for HIV and are in urgent need of prevention, treatment, and care services. The meta-analysis showed remarkable consistency and severity of the HIV disease burden among transgender women. FUNDING: Center for AIDS Research at Johns Hopkins and the Center for Public Health and Human Rights at the JHU Bloomberg School of Public Health.

Barlow, T., P. Upadhyay, et al. (2013). "External fixators in the treatment of midshaft clavicle non-unions: a systematic review." Eur J Orthop Surg Traumatol.

Non- or mal-union of the clavicle is reported to occur in up to 15 % of conservatively treated fractures: the purpose of this systematic review is to examine the evidence for the use of external fixation in the treatment of clavicular non-union. We performed a search of MEDLINE and Embase, including all papers using external fixators for the treatment of clavicular non-union. Four papers satisfied our eligibility criteria: three case series and one case-control study. Level of evidence and quality assessment scoring were performed using published methods. Due to the heterogeneity of the study populations and interventions, no attempt at meta-analysis was made. External fixation in hypertrophic non-union of the clavicle, but not atrophic non-union, appears to be a reasonable treatment option. A pragmatic, multicentre, randomised controlled trial comparing external fixation and open reduction internal fixation in the treatment of hypertrophic non-union of the clavicle would be valuable.

Barraud, D., P. E. Bollaert, et al. (2013). "Impact of the Administration of Probiotics on Mortality in Critically Ill Adult Patients: A Meta-analysis of Randomized Controlled Trials." Chest 143(3): 646-55.

BACKGROUND: The objective of this study was to systematically review and quantitatively synthesize all randomized controlled trials (RCTs) that have compared important outcomes in critically ill patients who received an administration of probiotics. METHODS: A systematic literature search of PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was conducted using specific search terms. Eligible studies were RCTs that compared the effect of prebiotics, probiotics, or synbiotics administration with control on ICU and hospital mortality rates in critically ill adult patients. Weighted mean differences (WMDs), pooled ORs, and 95% CIs were calculated using the Mantel-Haenszel fixed- and random-effects models. RESULTS: Thirteen trials with 1,439 patients were analyzed. Probiotics did not significantly reduce ICU (OR, 0.85; 95% CI, 0.63-1.15) or hospital (OR, 0.90; 95% CI, 0.65-1.23) mortality. By contrast, probiotics administration reduced the incidence of ICU-acquired pneumonia (OR, 0.58; 95% CI, 0.42-0.79) and was associated with a shorter stay in the ICU (WMD, -1.49 days; 95% CI, -2.12 to -0.87 days). Finally, probiotics use was not associated with a shorter duration of mechanical ventilation (WMD, -0.18 days; 95% CI, -1.72-1.36 days) or a shorter hospital length of stay (WMD, -0.45 days; 95% CI, -1.41-0.52 days). CONCLUSIONS: The present meta-analysis suggests that the administration of probiotics did not significantly reduce ICU or hospital mortality rates but did reduce the incidence of ICU-acquired pneumonia and ICU length of stay.

Barrera, T. L., J. M. Mott, et al. (2013). "A meta-analytic review of exposure in group cognitive behavioral therapy for posttraumatic stress disorder." Clin Psychol Rev 33(1): 24-32.

Although the efficacy of exposure is well established in individual cognitive behavioral treatments for posttraumatic stress disorder (PTSD), some clinicians and researchers have expressed concerns regarding the use of in-session disclosure of trauma details through imaginal exposure in group cognitive behavioral therapy (GCBT) for PTSD. Thus, the aim of the present study was to conduct a systematic review of the empirical support for GCBT in the treatment of PTSD and to compare GCBT protocols that encourage the disclosure of trauma details via in-session exposure to GCBT protocols that do not include in-session exposure. Randomized controlled trials that assessed the efficacy of GCBT for PTSD were included in the meta-analysis. A total of 651 participants with PTSD were included in the 12 eligible GCBT treatment conditions (5 conditions included in-group exposure, 7 conditions did not include in-group exposure). The overall pre-post effect size of GCBT for PTSD (ES=1.13 [SE=0.22, 95% CI: 0.69 to 1.56, p<.001]). suggests that GCBT is an effective intervention for individuals with PTSD. No significant differences in effect sizes were found between GCBT treatments that included in-group exposure and those that did not. Although the attrition rate was higher in treatments that included exposure in-group, this rate is comparable to attrition rates in individual CBT treatments and pharmacotherapy for PTSD. The results from this meta-analysis suggest that concerns about the potentially negative impact of group exposure may be unwarranted, and support the use of exposure-based GCBT as a promising treatment option for PTSD.

Barrowclough, C., R. Emsley, et al. (2013). "Does change in cannabis use in established psychosis affect clinical outcome?" Schizophr Bull 39(2): 339-48.

Background: Cannabis use has been identified as a potent predictor of the earlier onset of psychosis, but meta-analysis has not indicated that it has a clear effect in established psychosis. Aim: To assess the association between cannabis and outcomes, including whether change in cannabis use affects symptoms and functioning, in a large sample of people with established nonaffective psychosis and comorbid substance misuse. Methods: One hundred and sixty participants whose substance use included cannabis were compared with other substance users (n = 167) on baseline demographic, clinical, and substance use variables. The cannabis using subgroup was examined prospectively with repeated measures of substance use and psychopathology at baseline, 12 months, and 24 months. We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes. Results: Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms. Second, cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity, even when patients became abstinent. However, greater cannabis exposure was associated with worse functioning, albeit with a small effect size. Conclusions: We did not find evidence of an association between cannabis dose and psychotic symptoms, although greater cannabis dose was associated with worse psychosocial functioning, albeit with small effect size. It would seem that within this population, not everyone will demonstrate durable symptomatic improvements from reducing cannabis.

Bartels, S. A., T. J. Gardenbroek, et al. (2013). "Systematic review and meta-analysis of laparoscopic versus open colectomy with end ileostomy for non-toxic colitis." Br J Surg.

BACKGROUND: This review compared short-term outcomes after laparoscopic versus open subtotal colectomy for acute, colitis medically refractory. METHODS: A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases. Overall study quality was assessed by the modified Methodological Index for Non-Randomized Studies (MINORS). Meta-analysis was performed for conversion, reoperation, wound infection, ileus, gastrointestinal bleeding, intra-abdominal abscess, postoperative length of stay and mortality. RESULTS: The search identified nine non-randomized studies: six cohort studies and three case-matched series, comprising 966 patients in total. The pooled conversion rate was 5.5 (95 per cent confidence interval (c.i.) 3.6 to 8.4) per cent in the laparoscopic group. The pooled risk ratio of wound infection was 0.60 (95 per cent c.i. 0.38 to 0.95; P = 0.03) and that of intra-abdominal abscess was 0.27 (0.08 to 0.91; P = 0.04), both in favour of laparoscopic surgery. Pooled risk ratios for other complications showed no significant differences. Length of stay was significantly shorter after laparoscopic subtotal colectomy, with a pooled mean difference of 3.17 (95 per cent c.i. 2.37 to 3.98) days (P < 0.001). CONCLUSION: Where the procedure can be completed laparoscopically, there may be short-term benefits over open colectomy for colitis. These results cannot be generalized to critically ill patients in need of an emergency subtotal colectomy. Copyright (c) 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Bashir, M. K. and S. Schilizzi (2013). "Determinants of rural household food security: a comparative analysis of African and Asian studies." J Sci Food Agric.

This paper reviews the determinants of rural household food security in Africa and Asia where more than 88% of the world's undernourished people live. A conceptual model is proposed on the basis of the three widely known components of food security: food availability, accessibility and utilisation. This model is used to select a total of 40 peer-reviewed studies carried out over the last decade (20 each from Africa and Asia). A meta-analysis technique is then used to identify which determinants of food security have been highlighted and how well the causality is demonstrated. Food availability is the most studied component in both regions, followed by food accessibility, while food utilisation is the most neglected component in these studies. (c) 2013 Society of Chemical Industry.

Bastos, J., H. Carreira, et al. (2013). "Childcare attendance and Helicobacter pylori infection: systematic review and meta-analysis." Eur J Cancer Prev.

Helicobacter pylori infection is acquired predominantly during childhood. Childcare promotes interpersonal contact and may be an important determinant of infection. The aim was to quantify the association between childcare attendance and H. pylori infection in childhood or adolescence. PubMed was searched up to July 2012 to identify eligible studies. The DerSimonian and Laird method was used to compute summary odds ratio (OR) estimates and 95% confidence intervals (CIs); heterogeneity was quantified with the I statistic and explained through stratified analyses and metaregression. Sixteen studies compared participants attending childcare with those not exposed. The summary OR was 1.12 (95% CI: 0.82-1.52, I=77.4%). Summary estimates were similar for crude and adjusted estimates, and higher when the infection was evaluated in children of 3 years or younger (OR=2.00, 95% CI: 0.94-4.29, I=55.0%). Studies based on the detection of stool antigens yielded higher estimates (OR=2.65, 95% CI: 1.24-5.66, I=36.4%). Those conducted in settings with a high prevalence of H. pylori infection yielded stronger associations (OR=1.44, 95% CI: 0.94-2.20, I=74.3%). In multivariate metaregression, there was no significant association with any of these variables; taking them into account contributed to a reduction of I to 67%. The role of childcare as a risk factor for H. pylori infection is confirmed by our results, especially in settings with a high prevalence of infection. However, the association was moderate, and the effect of the type of childcare setting or the duration or the intensity of exposure was seldom addressed, leaving considerable scope for improving our understanding of how this modifiable exposure contributes towards H. pylori infection.

Basurto Ona, X., S. M. Uriona Tuma, et al. (2013). "Drug therapy for preventing post-dural puncture headache." Cochrane Database Syst Rev 2: CD001792.

BACKGROUND: Post-dural (post-lumbar or post-spinal) puncture headache (PDPH) is one of the most common complications of diagnostic, therapeutic or inadvertent lumbar punctures. Many drug options have been used to prevent headache in clinical practice and have also been tested in some clinical studies, but there are still some uncertainties about their clinical effectiveness. OBJECTIVES: To assess the effectiveness and safety of drugs for preventing PDPH in adults and children. SEARCH METHODS: The search strategy included the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 5), MEDLINE (from 1950 to May 2012), EMBASE (from 1980 to May 2012) and CINAHL (from 1982 to June 2012). There was no language restriction. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that assessed the effectiveness of any drug used for preventing PDPH. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because participants' characteristics or assessed doses of drugs were too different in the included studies. We performed an intention-to-treat (ITT) analysis. MAIN RESULTS: We included 10 RCTs (1611 participants) in this review with a majority of women (72%), mostly parturients (women in labour) (913), after a lumbar puncture for regional anaesthesia. Drugs assessed were epidural and spinal morphine, spinal fentanyl, oral caffeine, rectal indomethacin, intravenous cosyntropin, intravenous aminophylline and intravenous dexamethasone.All the included RCTs reported data on the primary outcome, i.e. the number of participants affected by PDPH of any severity after a lumbar puncture. Epidural morphine and intravenous cosyntropin reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to placebo. Also, intravenous aminophylline reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention, while intravenous dexamethasone increased it. Spinal morphine increased the number of participants affected by pruritus when compared to placebo, and epidural morphine increased the number of participants affected by nausea and vomiting when compared to placebo. Oral caffeine increased the number of participants affected by insomnia when compared to placebo.The remainder of the interventions analysed did not show any relevant effect for any of the outcomes.None of the included RCTs reported the number of days that patients stayed in hospital. AUTHORS' CONCLUSIONS: Morphine and cosyntropin have shown effectiveness for reducing the number of participants affected by PDPH of any severity after a lumbar puncture, when compared to placebo, especially in patients with high risk of PDPH, such as obstetric patients who have had an inadvertent dural puncture. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention in patients undergoing elective caesarean section. Dexamethasone increased the risk of PDPH, after spinal anaesthesia for caesarean section, when compared to placebo. Morphine also increased the number of participants affected by adverse events (pruritus and nausea and vomiting)There is a lack of conclusive evidence for the other drugs assessed (fentanyl, caffeine, indomethacin and dexamethasone).These conclusions should be interpreted with caution, owing to the lack of information, to allow correct appraisal of risk of bias and the small sample sizes of studies.

Batchelor, J. S. and A. Grayson (2013). "A meta-analysis to determine the effect of preinjury antiplatelet agents on mortality in patients with blunt head trauma." Br J Neurosurg 27(1): 12-8.

INTRODUCTION: Anticoagulation abnormalities have been recognized for several decades as potential risk factors for increasing the risk of traumatic intracranial haemorrhage in patients with blunt head trauma. The potential increased risk of death as a consequence has not been fully evaluated. The aim of the study was to perform a meta-analysis in order to evaluate based upon the current level of evidence whether the use of pre-injury aspirin or clopidogrel increases the risk of mortality in patients with blunt head trauma. METHODS: The databases Medline and EMBASE were searched via the Ovid interface. The Medline database was also searched using the PubMed interface. Case control studies or nested case control studies were identified comparing mortality rates on patients with blunt head trauma in patients on aspirin or clopidogrel against patients not on antiplatelet agents. RESULTS: Five studies in total were identified as suitable for the meta-analysis. Four of these studies were suitable for the aspirin meta-analysis and four for the clopidogrel meta-analysis. The common odds ratio for the aspirin meta-analysis using the Random Effects model was found to be 2.435 (95% CI: 0.637-9.314). Significant heterogeneity was present I(2) = 79.521. The common odds ratio for the clopidogrel meta-analysis using the Random Effects model was found to be 1.554 (95% CI: 0.320-7.536). Significant heterogeneity was present I(2) = 69.090. CONCLUSIONS: In summary, this meta-analysis showed a slight increased risk of death in patients with blunt head trauma who were taking pre-injury antiplatelet agents although the results did not reach statistical significance. In view of the small number of low level studies from which this meta-analysis is based, further work is required in this area.

Bauer, T. M., B. F. El-Rayes, et al. (2013). "Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials." Cancer 119(2): 285-92.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is a widely used biomarker in pancreatic cancer. There is no consensus on the interpretation of the change in CA19-9 serum levels and its role in the clinical management of patients with pancreatic cancer. METHODS: Individual patient data from 6 prospective trials evaluating gemcitabine-containing regimens from 3 different institutions were pooled. CA19-9 values were obtained at baseline and after successive cycles of treatment. The objective of this study was to correlate a decline in CA19-9 with outcomes while undergoing treatment. RESULTS: A total of 212 patients with locally advanced (n = 50) or metastatic (n = 162) adenocarcinoma of the pancreas were included. Median baseline CA19-9 level was 1077 ng/mL (range, 15-492,241 ng/mL). Groups were divided into those levels below (low) or above (high) the median. Median overall survival (mOS) was 8.7 versus 5.2 months (P = .0018) and median time to progression (mTTP) was 5.8 versus 3.7 months (P = .082) in the low versus high groups, respectively. After 2 cycles of chemotherapy, up to a 5% increase versus >/= 5% increase in CA19-9 levels conferred an improved mOS (10.3 vs 5.1 months, P = .0022) and mTTP (7.5 vs 3.5 months, P = 0.0005). CONCLUSIONS: In patients who have advanced pancreatic cancer treated with gemcitabine-containing regimens baseline CA19-9 is prognostic for outcome. A decline in CA19-9 after the second cycle of chemotherapy is not predictive of improved mOS or mTTP; thus, CA19-9 decline is not a useful surrogate endpoint in clinical trials. Clinically, a >/= 5% rise in CA19-9 after 2 cycles of chemotherapy serves as a negative predictive marker.

Beaton, C., C. P. Twine, et al. (2013). "Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer." Colorectal Dis.

AIM: Lymph node (LN) metastases are present in up to 17% of early colorectal cancers (pT1). Identification of associated histopathological factors would enable counseling of patients regarding this risk. METHOD: Pubmed and Embase were employed utilising the terms 'early colorectal cancer', 'lymph node metastasis', 'submucosal invasion', 'lymphovascular invasion', 'tumour budding' and 'histological differentiation'. Analysis was performed using Review Manager 5.1. RESULTS: Twenty three cohort studies including 4510 patients were analysed. There was a significantly higher risk of LN metastasis with a depth of submucosal invasion greater than 1mm than with lesser degrees of penetration (OR 3.87, 95% CI 1.50-10.00, p=0.005). Lymphovascular invasion was significantly associated with LN metastasis (OR 481, 314-737, p<000001). Poorly differentiated tumours had a higher risk of LN metastasis compared with well or moderately differentiated tumours (OR 5.60, 2.90-10.82, p<000001). Tumour budding was found to be significantly associated with LN metastasis (OR 774, 447-1339, p<0001). CONCLUSION: Meta-analysis of the current literature demonstrates that in early colorectal cancer a depth of submucosal invasion by the primary tumour of >1mm, lymphovascular invasion, poor differentiation and tumour budding are significantly associated with LN metastasis. (c) 2013 The Authors. Colorectal Disease (c) 2013 The Association of Coloproctology of Great Britain and Ireland.

Beck, A. H., N. W. Knoblauch, et al. (2013). "Significance analysis of prognostic signatures." PLoS Comput Biol 9(1): e1002875.

A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that "random" gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated genomic datasets.

Beck, A. M., M. Holst, et al. (2013). "Oral nutritional support of older (65 years+) medical and surgical patients after discharge from hospital: systematic review and meta-analysis of randomized controlled trials." Clin Rehabil 27(1): 19-27.

OBJECTIVE: To estimate the effectiveness of oral nutritional support compared to placebo or usual care in improving clinical outcome in older (65 years+) medical and surgical patients after discharge from hospital. Outcome goals were: re-admissions, survival, nutritional and functional status, quality of life and morbidity. DATA SOURCES: Three recent Cochrane reviews and an update of their literature search using MEDLINE, EMBASE, Web of Science. Search terms included randomized controlled trials; humans; age 65+ years; subset: dietary supplements. REVIEW METHODS: One reviewer assessed trials for inclusion, extracted data and assessed trial quality. RESULTS: Six trials were included (N = 716 randomly assigned participants). All trials used oral nutritional supplements. A positive effect on nutritional intake (energy) and/or nutritional status (weight) (in compliant participants) were observed in all trials. Two pooled analysis was based on a fixed-effects model. No significant effect were found on mortality (four randomized controlled trials with 532 participants, odds ratio 0.80 (95% confidence (CI) interval 0.46 to 1.39)) or re-admissions (four randomized controlled trials with 478 participants, odds ratio 1.07 (95% CI 0.71 to 1.61)). CONCLUSION: Although the evidence is limited, we suggest that oral nutritional support may be considered for older malnourished medical and surgical patients after discharge from hospital.

Beekman, M., H. Blanche, et al. (2013). "Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study." Aging Cell.

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 x 10(-8) ). By combined modeling of linkage and association, we showed that association of longevity with APOEepsilon4 and APOEepsilon2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 x 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.

Been, J. V., S. Lievense, et al. (2013). "Chorioamnionitis as a risk factor for necrotizing enterocolitis: a systematic review and meta-analysis." J Pediatr 162(2): 236-42 e2.

OBJECTIVE: To accumulate available evidence regarding the association between antenatal inflammation and necrotizing enterocolitis (NEC). STUDY DESIGN: A systematic literature search was performed using Medline, Embase, Cochrane Library, ISI Web of Knowledge, and reference hand searches. Human studies published in English that reported associations between chorioamnionitis or other indicators of antenatal inflammation and NEC were eligible. Relevant associations were extracted and reported. Studies reporting associations between histological chorioamnionitis (HC) and NEC, HC with fetal involvement and NEC, and clinical chorioamnionitis and NEC were pooled in separate meta-analyses. RESULTS: A total of 33 relevant studies were identified. Clinical chorioamnionitis was significantly associated with NEC (12 studies; n = 22 601; OR, 1.24; 95% CI, 1.01-1.52; P = .04; I(2) = 12%), but the association between HC and NEC was not statistically significant (13 studies; n = 5889; OR, 1.39; 95% CI, 0.95-2.04; P = .09; I(2) = 49%). However, HC with fetal involvement was highly associated with NEC (3 studies; n = 1640; OR, 3.29; 95% CI, 1.87-5.78; P </= .0001; I(2) = 10%). Selection based on study quality did not affect the results. No indications of publication bias were apparent. Multivariate analyses in single studies generally attenuated the reported associations. Several associations between other markers of antenatal inflammation and NEC are reported. CONCLUSION: Currently available evidence supports a role for antenatal inflammation in NEC pathophysiology. This finding emphasizes the need to further study the underlying mechanisms and evaluate potential interventions to improve postnatal intestinal outcomes.

Been, J. V., U. Nurmatov, et al. (2013). "The impact of smoke-free legislation on fetal, infant and child health: a systematic review and meta-analysis protocol." BMJ Open 3(2).

INTRODUCTION: Second-hand smoke (SHS) exposure is estimated to kill 600 000 people worldwide annually. The WHO recommends that smoke-free indoor public environments are enforced through national legislation. Such regulations have been shown to reduce SHS exposure and, consequently, respiratory and cardiovascular morbidity. Evidence of particular health benefit in children is now emerging, including reductions in low birthweight deliveries, preterm birth and asthma exacerbations. We aim to comprehensively assess the impact of smoke-free legislation on fetal, infant and childhood outcomes. This can inform further development and implementation of global policy and strategies to reduce early life SHS exposure. METHODS: Two authors will search online databases (1975-present; no language restrictions) of published and unpublished/in-progress studies, and references and citations to articles of interest. We will consult experts in the field to identify additional studies. Studies should describe associations between comprehensive or partial smoking bans in public places and health outcomes among children (0-12 years): stillbirth, preterm birth, low birth weight, small for gestational age, perinatal mortality, congenital anomalies, bronchopulmonary dysplasia, upper and lower respiratory infections and wheezing disorders including asthma. The Cochrane Effectiveness Practice and Organisational Care (EPOC)-defined study designs are eligible. Study quality will be assessed using the Cochrane 7-domain-based evaluation for randomised and clinical trials, and EPOC criteria for quasiexperimental studies. Data will be extracted by two reviewers and presented in tabular and narrative form. Meta-analysis will be undertaken using random-effects models, and generic inverse variance analysis for adjusted effect estimates. We will report sensitivity analyses according to study quality and design characteristics, and subgroup analyses according to coverage of ban, age group and parental/maternal smoking status. Publication bias will be assessed. ETHICS AND DISSEMINATION: Ethics assessment is not required. RESULTS: Will be presented in one manuscript. The protocol is registered with PROSPERO, registration number CRD42013003522.

Behrens, G. and M. F. Leitzmann (2013). "The association between physical activity and renal cancer: systematic review and meta-analysis." Br J Cancer 108(4): 798-811.

Background:Physical activity may decrease renal cancer risk by reducing obesity, blood pressure, insulin resistance, and lipid peroxidation. Despite plausible biologic mechanisms linking increased physical activity to decreased risk for renal cancer, few epidemiologic studies have been able to report a clear inverse association between physical activity and renal cancer, and no meta-analysis is available on the topic.Methods:We searched the literature using PubMed and Web of Knowledge to identify published non-ecologic epidemiologic studies quantifying the relationship between physical activity and renal cancer risk in individuals without a cancer history. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, including information from 19 studies based on a total of 2 327 322 subjects and 10 756 cases. The methodologic quality of the studies was examined using a comprehensive scoring system.Results:Comparing high vs low levels of physical activity, we observed an inverse association between physical activity and renal cancer risk (summary relative risk (RR) from random-effects meta-analysis=0.88; 95% confidence interval (CI)=0.79-0.97). Summarising risk estimates from high-quality studies strengthened the inverse association between physical activity and renal cancer risk (RR=0.78; 95% CI=0.66-0.92). Effect modification by adiposity, hypertension, type 2 diabetes, smoking, gender, or geographic region was not observed.Conclusion:Our comprehensive meta-analysis provides strong support for an inverse relation of physical activity to renal cancer risk. Future high-quality studies are required to discern which specific types, intensities, frequencies, and durations of physical activity are needed for renal cancer risk reduction.

Belkhair, S. and G. Pickett (2013). "One versus double burr holes for treating chronic subdural hematoma meta-analysis." Can J Neurol Sci 40(1): 56-60.

OBJECTIVE AND DESIGN: There is controversy among neurosurgeons regarding whether double burr hole craniostomy (DBHC) is better than single burr hole craniostomy (SBHC) in the treatment of chronic subdural hematoma (CSH), in terms of having a lower revision rate. In order to compare the revision rates after SBHC versus DBHC, we performed a meta-analysis of the available studies in the literature. MATERIALS AND METHODS: Multiple electronic health databases were searched to identify all the studies published between 1966 and December 2010 that compared SBHC and DBHC. Data were processed in Review Manager 5.0.18. Effect sizes were expressed in pooled odds ratio (OR) estimates, and due to heterogeneity between studies we used random effect of the inverse variance weighted method to perform the meta-analysis. RESULTS: Five observational retrospective cohort studies were identified: four published studies and one unpublished, describing the outcomes of 355 DBHC and 358 SBHC to evacuate 713 CSH in 631 patients. Meta-analysis showed that there was no significant difference in the revision rates between double burr hole craniostomy and single burr hole craniostomy when performed to evacuate CSH. Pooled odds ratio for all the studies was 0.62 (95% confidence interval 0.26 - 1.46). CONCLUSIONS: The results of this meta-analysis suggest that SBHC is as good as DBHC in evacuating chronic subdural hematoma and is not associated with a higher revision rate compared to DBHC.

Bendsen, N. T., R. Christensen, et al. (2013). "Is beer consumption related to measures of abdominal and general obesity? A systematic review and meta-analysis." Nutr Rev 71(2): 67-87.

A systematic review was conducted to assess the evidence linking beer consumption to abdominal and general obesity. Following a systematic search strategy, 35 eligible observational studies and 12 experimental studies were identified. Regarding abdominal obesity, most observational data pointed towards a positive association or no association between beer intake and waist circumference or waist-to-hip ratio in men, whereas results for women were inconsistent. Data from a subset of studies indicated that beer intake > 500 mL/day may be positively associated with abdominal obesity. Regarding general obesity, most observational studies pointed towards an inverse association or no association between beer intake and body weight in women and a positive association or no association in men. Data from six experimental studies in men, in which alcoholic beer was compared with low-alcoholic beer, suggested that consumption of alcoholic beer (for 21-126 days) results in weight gain (0.73 kg; P < 0.0001), but data from four studies comparing intake of alcoholic beer with intake of no alcohol did not support this finding. Generally, experimental studies had low-quality data. In conclusion, the available data provide inadequate scientific evidence to assess whether beer intake at moderate levels (<500 mL/day) is associated with general or abdominal obesity. Higher intake, however, may be positively associated with abdominal obesity.

Benedetto, U., E. Angeloni, et al. (2013). "n-3 Polyunsaturated fatty acids for the prevention of postoperative atrial fibrillation: a meta-analysis of randomized controlled trials." J Cardiovasc Med (Hagerstown) 14(2): 104-9.

BACKGROUND: n-3 Polyunsaturated fatty acids (n-3 PUFAs) have been proposed as prophylactic therapy in the prevention of postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery. We conducted a meta-analysis of randomized controlled trials to better clarify this issue. METHODS: An electronic database search for randomized controlled trials on the effect of n-3 PUFAS on POAF was conducted, limited to English language publications until December 2010. For each study, data regarding the incidence of POAF were used to generate risk ratio (<1, favors n-3 PUFA; >1, favors placebo). Pooled summary effect estimate was calculated by means of a fixed or random effect according to heterogeneity. Meta-regression was used to investigate the effect of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ratio and preoperative beta-blockers on the effect of n-3 PUFA on POAF. RESULTS: Three publications were included in the analysis, enrolling a total of 431 patients. Overall incidence of POAF ranged from 24 to 54%. Pooling data, n-3 PUFA did not show a significant effect on the risk of POAF [risk ratio 0.89; 95% confidence interval (CI) 0.55-1.44; P=0.63]. However, meta-regression analysis showed a trend toward a benefit from n-3 PUFA supplementation when the EPA/DHA ratio was 1:2 (Q model=7.4; p model=0.02) and when preoperative beta-blocker rate was lower (Q model=8.0; p model=0.01). CONCLUSION: In conclusion, the results of the present meta-analysis of randomized controlled trials suggest that preoperative n-3 PUFA therapy may not reduce POAF in patients undergoing cardiac surgery. However, several aspects may have influenced this negative result, which need to be investigated.

Benedetto, U., G. Melina, et al. (2013). "Current results of open total arch replacement versus hybrid thoracic endovascular aortic repair for aortic arch aneurysm: a meta-analysis of comparative studies." J Thorac Cardiovasc Surg 145(1): 305-6.

Bennett, M. M., B. J. Crowe, et al. (2013). "Comparison of bayesian and frequentist meta-analytical approaches for analyzing time to event data." J Biopharm Stat 23(1): 129-45.

Using meta-analysis in health care research is a common practice. Here we are interested in methods used for analysis of time-to-event data. Particularly, we are interested in their performance when there is a low event rate. We consider three methods based on the Cox proportional hazards model, including a Bayesian approach. A formal comparison of the methods is conducted using a simulation study. In our simulation we model two treatments and consider several scenarios.

Benzies, K. M., J. E. Magill-Evans, et al. (2013). "Key components of early intervention programs for preterm infants and their parents: a systematic review and meta-analysis." BMC Pregnancy Childbirth 13 Suppl 1: S10.

BACKGROUND: Preterm infants are at greater risk for neurodevelopmental disabilities than full term infants. Interventions supporting parents to improve the quality of the infant's environment should improve developmental outcomes for preterm infants. Many interventions that involve parents do not measure parental change, nor is it clear which intervention components are associated with improved parental outcomes. The aim of this review was to categorize the key components of early intervention programs and determine the direct effects of components on parents, as well as their preterm infants. METHODS: MEDLINE, EMBASE, CINAHL, ERIC, and Cochrane Database of Systematic Reviews were searched between 1990 and December 2011. Eligible randomized controlled trials (RCTs) included an early intervention for preterm infants, involved parents, and had a community component. Of 2465 titles and abstracts identified, 254 full text articles were screened, and 18 met inclusion criteria. Eleven of these studies reported maternal outcomes of stress, anxiety, depressive symptoms, self-efficacy, and sensitivity/responsiveness in interactions with the infant. Meta-analyses using a random effects model were conducted with these 11 studies. RESULTS: Interventions employed multiple components categorized as (a) psychosocial support, (b) parent education, and/or (c) therapeutic developmental interventions targeting the infant. All interventions used some form of parenting education. The reporting quality of most trials was adequate, and the risk of bias was low based on the Cochrane Collaboration tool. Meta-analyses demonstrated limited effects of interventions on maternal stress (Z = 0.40, p = 0.69) and sensitivity/responsiveness (Z = 1.84, p = 0.07). There were positive pooled effects of interventions on maternal anxiety (Z = 2.54, p = 0.01), depressive symptoms (Z = 4.04, p <.0001), and self-efficacy (Z = 2.05, p = 0.04). CONCLUSIONS: Positive and clinically meaningful effects of early interventions were seen in some psychosocial aspects of mothers of preterm infants. This review was limited by the heterogeneity of outcome measures and inadequate reporting of statistics. IMPLICATIONS OF KEY FINDINGS: Interventions for preterm infants and their mothers should consider including psychosocial support for mothers. If the intervention involves mothers, outcomes for both mothers and preterm infants should be measured to better understand the mechanisms for change.

Bercik, M. J., A. Joshi, et al. (2013). "Posterior cruciate-retaining versus posterior-stabilized total knee arthroplasty: a meta-analysis." J Arthroplasty 28(3): 439-44.

The objective of this meta-analysis was to compare outcomes of posterior cruciate-retaining and posterior stabilized prostheses. A computerized literature search was conducted to identify randomized controlled trials comparing the clinical outcomes of cruciate-retaining and posterior-stabilized designs. The table of contents of four major Orthopaedic journals and the references section of two arthroplasty text books were reviewed to identify other relevant studies. Ultimately, 1114 patients (1265 knees) were compared. Statistical analysis revealed a significant difference in flexion and range of motion in favor of posterior-stabilized knees, but no difference in complication rates. The clinical importance of this remains unknown. The decision to use one design versus the other should rest with the surgeon's preference and comfort with a particular design.

Berghella, V., J. K. Baxter, et al. (2013). "Cervical assessment by ultrasound for preventing preterm delivery." Cochrane Database Syst Rev 1: CD007235.

BACKGROUND: Measurement of cervical length (CL) by transvaginal ultrasound (TVU) is predictive of preterm birth (PTB). It is unclear if this screening test is effective for prevention of PTB. OBJECTIVES: To assess the effectiveness of antenatal management based on transvaginal ultrasound of cervical length (TVU CL) screening for preventing PTB. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2012), reviewed the reference lists of all articles and contacted experts in the field for additional and ongoing trials. SELECTION CRITERIA: Published and unpublished randomized controlled trials including pregnant women between the gestational ages of 14 to 32 weeks screened with TVU CL for risk of PTB. This review focuses exclusively on studies based on knowledge versus no knowledge of TVU CL results. DATA COLLECTION AND ANALYSIS: All potential studies identified from the search were independently assessed for inclusion by three review authors. We also analyzed studies for quality measures and extracted data. MAIN RESULTS: Of the 13 trials identified, five were eligible for inclusion (n = 507). Three included singleton gestations with preterm labor (PTL); one included singleton gestations with preterm premature rupture of membranes (PPROM); and one included twin gestations with or without PTL.In the three trials of singleton gestations with PTL, 290 women were randomized; 147 to knowledge and 143 to no knowledge of TVU CL. Knowledge of TVU CL results was associated with a non-significant decrease in PTB at less than 37 weeks (22.3% versus 34.7%, respectively; average risk ratio 0.59, 95% confidence interval (CI) 0.26 to 1.32; two trials, 242 women) and at less than 34 weeks (6.9% verus 12.6%; RR 0.55, 95% CI 0.25 to 1.20; three trials, 256 women). Delivery occurred at a later gestational age in the knowledge versus no knowledge groups (mean difference (MD) 0.64 weeks, 95% CI 0.03 to 1.25; three trials, 290 women). For all other outcomes for which there were available data (PTB at less than 34 or 28 weeks; birthweight less than 2500 grams; perinatal death; maternal hospitalization; tocolysis; and steroids for fetal lung maturity), there was no evidence of a difference between groups.The trial of singleton gestations with PPROM (n = 92) evaluated as its primary outcome safety of TVU CL in this population, and not its effect on management. There was no evidence of a difference in incidence of maternal and neonatal infections between the TVU CL and no TVU CL groups.In the trial of twin gestations with or without PTL (n = 125), there was no evidence of a difference in PTB at less than 36, 34, or 30 weeks, gestational age at delivery, and other perinatal and maternal outcomes between the TVU CL and the no TVU CL groups. Life-table analysis revealed significantly less PTB at less than 35 weeks in the TVU CL group compared with the no TVU CL group (P = 0.02). AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to recommend routine screening of asymptomatic or symptomatic pregnant women with TVU CL. Since there is a non-significant association between knowledge of TVU CL results and a lower incidence of PTB at less than 37 weeks in symptomatic women, we encourage further research. Future studies should look at specific populations separately (e.g., singleton versus twins; symptoms of PTL or no such symptoms), report on all pertinent maternal and perinatal outcomes, and include cost-effectiveness analyses. Most importantly, future studies should include a clear protocol for management of women based on TVU CL results, so that it can be easily evaluated and replicated.

Berhan, A. and Y. Berhan (2013). "Efficacy of alogliptin in type 2 diabetes treatment: a meta-analysis of randomized double-blind controlled studies." BMC Endocr Disord 13(1): 9.

BACKGROUND: Alogliptin is a new dipeptidyl peptidase (DPP-4) inhibitor, which is under investigation for treatment of type 2 diabetes either alone or in combination with other antidiabetic drugs. The aim of this meta-analysis was to assess the efficacy and tolerability of alogliptin in patients with type 2 diabetes. METHODS: Computer based search was performed in MEDLINE, Cochrane library, and HINARI (Health InterNetwork Access to Research Initiative) databases. Meta-analysis was carried out by incorporating double-blind randomized controlled studies done on the efficacy of alogliptin in patients with type 2 diabetes. The efficacy and tolerability of alogliptin was determined by standardized mean differences (SMDs) and Mantel-Haenszel odds ratio. Heterogeneity was assessed by the chi-squared test (Cochran Q test) and I2 statistics. RESULTS: The pooled SMDs demonstrated a significant reduction in HbA1c in patients treated with alogliptin 12.5 mg (SMD = -0.81; 95% CI, -1.11 to -0.51) or alogliptin 25 mg (SMD= -0.98; 95%CI= -1.30 to -0.66) as compared with controls. The SMD for reduction in fasting plasma glucose level (FPG) from baseline was also statistically significant among alogliptin treated patients. However, the effect of alogliptin on body weight change was inconclusive. The proportion of patients who discontinued alogliptin due to adverse events was not different from controls. Similarly, the meta-analyses of specific adverse events did not demonstrate statistically significant differences. CONCLUSIONS: Alogliptin alone or in combination with other antidiabetic drug has shown a significant reduction in HbA1c and FPG level in patients with type 2 diabetes. However, its consistent efficacy for longer duration of therapy needs further investigation.

Berhan, Y. and A. Berhan (2013). "Meta-analysis on risky sexual behaviour of men: consistent findings from different parts of the world." AIDS Care 25(2): 151-9.

The aim of this analysis was to determine the consistency of higher-risk sex practice among educated and/or wealthy men in different parts of the world. Meta-analysis was done on risky sexual behaviour of men using the recent Demographic and Health Surveys (DHS 2003-2009) data from 26 countries in and outside Africa. DHS data were accessed through electronic databases. In this analysis, since there was significant heterogeneity (I(2)>50%) among surveys findings, random effects analytic model was applied. Mantel-Haenszel statistical method was used to calculate the pooled odds ratios across countries. Out of 79,736 men aged 15-49 years who had sexual intercourse in 12 months preceding the respective survey, 35.7% reported to have higher-risk sex. The proportion of higher-risk sex was found positively correlated with increased wealth index. In 24 countries, higher-risk sex was found to have highly statistically significant association with men living in urban areas, educated to secondary and above, and owned middle to highest wealth index. The overall condom use during the last higher-risk sexual encounter was 47% but condom use was better practiced by educated men. Nearly in two-thirds of countries reported HIV-prevalence, the proportion of HIV infection was highest among better educated. In conclusion, this meta-analysis has shown that risk taking sexual behaviour is invariably associated with high educational attainment, urban residence and better wealth index regardless of geographic location of men participated in the surveys.

Berlim, M. T., H. J. Broadbent, et al. (2013). "Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis." Int J Neuropsychopharmacol: 1-9.

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depression (MD). However, the perceived lack of a suitable sham rTMS condition might have compromised the success of blinding procedures in clinical trials. Thus, we conducted a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials (RCTs) on high frequency (HF-), low frequency (LF-) and bilateral rTMS for MD. We searched the literature from January 1995 to July 2012 using Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and Scopus. The main outcome measure was participants' ability to correctly guess their treatment allocation at study end. We used a random-effects model and risk difference (RD). Overall, data were obtained from seven and two RCTs on HF- and bilateral rTMS, respectively. No RCT on LF-rTMS reporting on blinding success was found. HF- and bilateral rTMS trials enrolled 396 and 93 depressed subjects and offered an average of approximately 13 sessions. At study end, 52 and 59% of subjects receiving HF-rTMS and sham rTMS were able to correctly guess their treatment allocation, a non-significant difference (RD = -0.04; z = -0.51; p = 0.61). Furthermore, 63.3 and 57.5% of subjects receiving bilateral and sham rTMS were able to correctly guess their treatment allocation, also a non-significant difference (RD = 0.05; z = 0.49; p = 0.62). In addition, the use of angulation and sham coil in HF-rTMS trials produced similar results. In summary, existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation.

Berlim, M. T., F. Van den Eynde, et al. (2013). "Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials." J Psychiatr Res 47(1): 1-7.

OBJECTIVE: tDCS is a promising novel therapeutic intervention for major depression (MD). However, clinical trials to date have reported conflicting results concerning its efficacy, which likely resulted from low statistical power. Thus, we carried out a systematic review and meta-analysis on randomized, double-blind and controlled trials of tDCS in MD with a focus on clinically relevant outcomes, namely response and remission rates. METHOD: We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on tDCS for treating MD from 1998 through July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and SCOPUS. We also consulted the Web of Science's Citations Index Expanded for the selected RCTs up to July 2012. The main outcome measures were response and remission rates. We used a random-effects model and Odds Ratios (OR). RESULTS: Data were obtained from 6 RCTs that included a total of 200 subjects with MD. After an average of 10.8 +/- 3.76 tDCS sessions, no significant difference was found between active and sham tDCS in terms of both response (23.3% [24/103] vs. 12.4% [12/97], respectively; OR = 1.97; 95% CI = 0.85-4.57; p = 0.11) and remission (12.2% [12/98] vs. 5.4% [5/92], respectively; OR = 2.13; 95% CI = 0.64-7.06; p = 0.22). Also, no differences between mean baseline depression scores and dropout rates in the active and sham tDCS groups were found. Furthermore, sensitivity analyses excluding RCTs that involved less than 10 treatment sessions or stimulus intensity of less than 2 mA did not alter the findings. However, tDCS used as monotherapy was associated with higher response rates when compared to sham tDCS (p = 0.043). Finally, the risk of publication bias in this meta-analysis was found to be low. CONCLUSIONS: The clinical utility of tDCS as a treatment for MD remains unclear when clinically relevant outcomes such as response and remission rates are considered. Future studies should include larger and more representative samples, investigate how tDCS compares to other therapeutic neuromodulation techniques, as well as identify optimal stimulation parameters.


Clinical trials comparing the efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) for treating major depression (MD) have yielded conflicting results. As this may have been the result of limited statistical power, we have carried out this meta-analysis to examine this issue. We searched the literature for randomized trials on head-to-head comparisons between HF-rTMS and ECT from January 1995 through September 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and SCOPUS. The main outcome measures were remission rates, pre-post changes in depression ratings, as well as overall dropout rates at study end. We used a random-effects model, Odds Ratios (OR), Number Needed to Treat (NNT), and Hedges' g effect sizes. Data were obtained from 7 randomized trials, totalling 294 subjects with MD. After an average of 15.2 HF-rTMS and 8.2 ECT sessions, 33.6% (38/113) and 52% (53/102) of subjects were classified as remitters (OR = 0.46; p = 0.04), respectively. The associated NNT for remission was 6 and favoured ECT. Also, reduction of depressive symptomatology was significantly more pronounced in the ECT group (Hedges' g = -0.93; p = 0.007). No differences on dropout rates for HF-rTMS and ECT groups were found. In conclusion, ECT seems to be more effective than HF-rTMS for treating MD, although they did not differ in terms of dropout rates. Nevertheless, future comparative trials with larger sample sizes and better matching at baseline, longer follow-ups and more intense stimulation protocols are warranted.

Berlim, M. T., F. Van den Eynde, et al. (2013). "High-frequency repetitive transcranial magnetic stimulation accelerates and enhances the clinical response to antidepressants in major depression: a meta-analysis of randomized, double-blind, and sham-controlled trials." J Clin Psychiatry 74(2): e122-9.

OBJECTIVE: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a safe and effective treatment for major depression. However, its utility as a strategy to accelerate and improve clinical response to antidepressants is still unclear. DATA SOURCES: We searched the literature from 1995 through May 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Scopus, and ProQuest Dissertations and Theses, and, from October 2008 until May 2012, by using MEDLINE. We included only studies written in the English language. STUDY SELECTION: We selected all randomized, double-blind, and sham-controlled trials on HF-rTMS used as an accelerating (add-on) strategy to antidepressants for major depression. DATA EXTRACTION: We performed a random effects meta-analysis using odds ratios (ORs) for response and remission rates following HF-rTMS and sham rTMS. Two time points were considered: the end of the add-on HF-rTMS stimulation period (T1) and the end of the study (T2). RESULTS: Data were obtained from 6 randomized controlled trials (RCTs), totaling 392 subjects with major depression. For T1 (at mean +/- SD 2.67 +/- 0.82 weeks following start of combined rTMS + antidepressant treatment), 6 studies reported on response and 4 on remission rates. We found significantly higher response rates for active HF-rTMS (43.3%; 84/194) compared to sham rTMS (26.8%; 53/198) (OR = 2.5; 95% CI, 1.12-5.56; P = .025); however, remission rates did not differ between groups (P = .33). Heterogeneity between the included RCTs reporting data on response and remission rates at T1 was significant (response: Q5 = 11.4, P = .044, I2 = 56.12; remission: Q3 = 12.24, P = .007, I2 = 75.45). For study end (T2; at mean +/- SD 6.80 +/- 3.11 weeks following start of combined rTMS + antidepressant treatment), 5 studies reported on response and 4 on remission rates; overall, response rates at T2 were significantly higher for subjects receiving HF-rTMS in comparison to those receiving sham rTMS (62% [104/168] and 46% [79/172], respectively; OR = 1.9; 95% CI, 1.003-3.56; P = .049). Also, 53.8% (57/106) and 38.64% (36/107) of subjects receiving active HF-rTMS and sham rTMS, respectively, were in remission at T2 (OR = 2.42; 95% CI, 1.27-4.61; P = .007). Heterogeneity between the included RCTs reporting data on remission rates at T2 was not significant, although RCTs reporting on response rates at T2 were heterogeneous. The baseline depression scores for active and sham rTMS groups were similar. Finally, HF-rTMS was comparable to sham rTMS in terms of dropout rates. CONCLUSIONS: HF-rTMS is a promising strategy for accelerating clinical response to antidepressants in major depression, providing clinically meaningful benefits that are comparable to those of other agents such as triiodothyronine and pindolol. Furthermore, HF-rTMS seems to be an acceptable treatment for depressed subjects.

Berlim, M. T., F. Van den Eynde, et al. (2013). "Clinically Meaningful Efficacy and Acceptability of Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Primary Major Depression: A Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials." Neuropsychopharmacology 38(4): 543-51.

Clinical trials on low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the right dorsolateral prefrontal cortex have yielded conflicting evidence concerning its overall efficacy for treating major depression (MD). As this may have been the result of limited statistical power of individual trials, we have carried the present systematic review and meta-analysis to examine this issue. We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on LF-rTMS for treating MD from 1995 through July 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses, and from October 2008 until July 2012 using MEDLINE. The main outcome measures were response and remission rates as well as overall dropout rates at study end. We used a random-effects model, odds ratios (ORs) and number needed to treat (NNT). Data were obtained from eight RCTs, totaling 263 subjects with MD. After an average of 12.6+/-3.9 rTMS sessions, 38.2% (50/131) and 15.1% (20/132) of subjects receiving active LF-rTMS and sham rTMS were classified as responders (OR=3.35; 95% CI=1.4-8.02; p=0.007). Also, 34.6% (35/101) and 9.7% (10/103) of subjects receiving active LF-rTMS and sham rTMS were classified as remitters (OR=4.76; 95% CI=2.13-10.64; p<0.0001). The associated NNT for both response and remission rates was 5. Sensitivity analyses have shown that protocols delivering >1200 magnetic pulses in total as well as those offering rTMS as a monotherapy for MD were associated with higher rates of response to treatment. No differences on mean baseline depression scores and dropout rates for active and sham rTMS groups were found. Finally, the risk of publication bias was low. In conclusion, LF-rTMS is a promising treatment for MD, as it provides clinically meaningful benefits that are comparable to those of standard antidepressants and high-frequency rTMS. Furthermore, LF-rTMS seems to be an acceptable intervention for depressed subjects.

Berlin, J. A., B. J. Crowe, et al. (2013). "Meta-analysis of clinical trial safety data in a drug development program: answers to frequently asked questions." Clin Trials 10(1): 20-31.

BACKGROUND: Meta-analyses of clinical trial safety data have risen in importance beyond regulatory submissions. During drug development, sponsors need to recognize safety signals early and adjust the development program accordingly, so as to facilitate the assessment of causality. Once a product is marketed, sponsors add postapproval clinical trial data to the body of information to help understand existing safety concerns or those that arise from other postapproval data sources, such as spontaneous reports. PURPOSE: This article focuses on common questions encountered when designing and performing a meta-analysis of clinical trial safety data. Although far from an exhaustive set of questions, they touch on some basic and often misunderstood features of conducting such meta-analyses. METHODS: The authors reviewed the current literature and used their combined experience with regulatory and other uses of meta-analysis to answer common questions that arise when performing meta-analyses of safety data. RESULTS: We addressed the following topics: choice of studies to pool, effects of the method of ascertainment, use of patient-level data compared to trial-level data, the need (or not) for multiplicity adjustments, heterogeneity of effects and sources of it, and choice of fixed effects versus random effects. LIMITATIONS: The list of topics is not exhaustive and the opinions offered represent only our perspective; we recognize that there may be other valid perspectives. CONCLUSIONS: Meta-analysis can be a valuable tool for evaluating safety questions, but a number of methodological choices need to be made in designing and conducting any meta-analysis. This article provides advice on some of the more commonly encountered choices.

Bermingham, S. L., S. Hodgkinson, et al. (2013). "Intermittent self catheterisation with hydrophilic, gel reservoir, and non-coated catheters: a systematic review and cost effectiveness analysis." BMJ 346: e8639.

OBJECTIVE: To determine the most effective and cost effective type of catheter for patients performing intermittent self catheterisation in the community. DESIGN: Systematic review and meta-analysis. Results were incorporated into a probabilistic Markov model to compare lifetime costs and quality adjusted life years (QALYs). DATA SOURCES: We searched Medline, Embase, and Cochrane and Cinahl databases from 2002 to 18 April 2011 to identify studies comparing hydrophilic, gel reservoir, and non-coated intermittent catheters. Earlier guidelines were used to identify papers published before 2002. To capture studies comparing clean and sterile non-coated intermittent self catheterisation, each database was searched from its date of inception to 18 April 2011. MAIN OUTCOME MEASURES: Clinical outcomes included symptomatic urinary tract infection (UTI), bacteraemia, mortality, patient preference or comfort, and number of catheters used. The economic model included downstream complications of UTI and cost effectiveness was calculated as incremental cost per QALY gained. RESULTS: Eight studies were included in the systematic review. Most were conducted in patients with spinal cord injuries, and most of the included patients were men. People using gel reservoir and hydrophilic catheters were significantly less likely to report one or more UTIs compared with sterile non-coated catheters (absolute effect for gel reservoir = 149 fewer per 1000 (95% confidence interval -7 to 198), P=0.04; absolute effect for hydrophilic = 153 fewer per 1000 (-8 to 268), P=0.04). However, there was no difference between hydrophilic and sterile non-coated catheters when outcomes were measured as mean monthly UTIs (mean difference = 0.01 (-0.11 to 0.09), P=0.84) or total UTIs at 1 year (mean difference = 0.18 (-0.50 to 0.86), P=0.60). There was little difference in the incidence of one or more UTIs for people using clean versus sterile non-coated catheters (absolute effect = 12 fewer per 1000 (-134 to 146), P=0.86). Although the most effective, gel reservoir catheters cost > pound54,350 per QALY gained and are therefore not cost effective compared with clean non-coated self catheterisation. CONCLUSION: The type of catheter used for intermittent self catheterisation seems to make little difference to the risk of symptomatic UTI. Given large differences in resource use, clean non-coated catheters are most cost effective. However, because of limitations and gaps in the evidence base and the designation of non-coated catheters as single use devices, we recommend a precautionary principle should be adopted and that patients should be offered a choice between hydrophilic and gel reservoir catheters.

Bernard, J. A. and R. D. Seidler (2013). "Cerebellar contributions to visuomotor adaptation and motor sequence learning: an ALE meta-analysis." Front Hum Neurosci 7: 27.

Cerebellar contributions to motor learning are well-documented. For example, under some conditions, patients with cerebellar damage are impaired at visuomotor adaptation and at acquiring new action sequences. Moreover, cerebellar activation has been observed in functional MRI (fMRI) investigations of various motor learning tasks. The early phases of motor learning are cognitively demanding, relying on processes such as working memory, which have been linked to the cerebellum as well. Here, we investigated cerebellar contributions to motor learning using activation likelihood estimation (ALE) meta-analysis. This allowed us to determine, across studies and tasks, whether or not the location of cerebellar activation is constant across differing motor learning tasks, and whether or not cerebellar activation in early learning overlaps with that observed for working memory. We found that different regions of the anterior cerebellum are engaged for implicit and explicit sequence learning and visuomotor adaptation, providing additional evidence for the modularity of cerebellar function. Furthermore, we found that lobule VI of the cerebellum, which has been implicated in working memory, is activated during the early stages of explicit motor sequence learning. This provides evidence for a potential role for the cerebellum in the cognitive processing associated with motor learning. However, though lobule VI was activated across both early explicit sequence learning and working memory studies, there was no spatial overlap between these two regions. Together, our results support the idea of modularity in the formation of internal representations of new motor tasks in the cerebellum, and highlight the cognitive processing relied upon during the early phases of motor skill learning.

Berry, D. P. and J. J. Crowley (2013). "Genetics of feed efficiency in dairy and beef cattle." J Anim Sci.

Increasing food production for the growing human population off a constraining land-base will require greater efficiency of production. Genetic improvement of feed efficiency in cattle, which is cumulative and permanent, is one likely vehicle to achieving efficiency gains. The objective of this review is to summarize genetic parameters for feed efficiency traits in dairy and beef cattle but also to address some of the misconceptions associated with feed efficiency in these sectors, as well as discuss the potential use of feed efficiency in breeding programs. A meta-analysis of up to 39 scientific publications in growing cattle clearly showed that genetic variation in feed efficiency exists with a pooled heritability for residual feed intake (RFI) and feed conversion efficiency of 0.33 +/- 0.01 (range of 0.07 to 0.62) and 0.23 +/- 0.01 (range of 0.06 to 0.46), respectively. Heritability estimates for feed efficiency in cows were lower; a meta-analysis of up to 11 estimates revealed heritability estimates for gross feed efficiency and RFI of 0.06 +/- 0.010 and 0.04 +/- 0.008, respectively. Meta-analysis of genetic correlations between feed intake, feed efficiency and other performance traits are presented and selection index theory is used to calculate the proportion of genetic variation in feed intake that can be explained by easy to measure, and often already collected data. A large proportion of the genetic variation in feed intake could be explained in both growing animals and lactating animals using up to 5 predictor traits including live-weight, growth rate, milk yield, body composition, and linear type traits reflecting body size and muscularity. Knowledge of genetic merit for feed intake can be used, along with estimates of genetic merit for energy sinks, to calculate genetic merit for feed efficiency. Therefore the marginal benefit of collecting actual feed intake data, using the genetic parameters used in this study, appears to be low. There is now sufficient information available to develop a roadmap on how best to direct research to ensure long-term food security for a growing human population. Gaps in knowledge are identified here and possibilities to address these gaps are discussed.

Berry, S. M., K. Broglio, et al. (2013). "A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression." Med Devices (Auckl) 6: 17-35.

To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy(R) plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models. Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients. A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit. Response was based on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions scale's Improvement subscale (CGI-I), as these were the two clinician-rated measures common across all or most studies. Remission was based on the MADRS. Outcomes were compared from baseline up to 96 weeks of treatment with VNS + TAU (n = 1035) versus TAU (n = 425). The MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%, 18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24, 48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was associated with a greater likelihood of response (odds ratio [OR] = 3.19, 95% confidence interval [CI]: 2.12, 4.66) and remission (OR = 4.99, CI: 2.93, 7.76), compared with TAU. For patients who had responded to VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks (OR = 1.98, CI: 1.34, 3.01) and at 96 weeks (OR = 3.42, CI: 1.78, 7.31). Similar results were observed for CGI-I response. For patients with chronic TRD, VNS + TAU has greater response and remission rates that are more likely to persist than TAU.

Besnard, A. E., S. A. Wirjosoekarto, et al. (2013). "Lecithin/sphingomyelin ratio and lamellar body count for fetal lung maturity: a meta-analysis." Eur J Obstet Gynecol Reprod Biol.

OBJECTIVE: To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) in the prediction of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: A systematic review was performed to identify studies comparing either the L/S ratio or the LBC with the occurrence of RDS published between January 1999 and February 2009. Two independent reviewers performed study selection and data extraction. For each study sensitivity and specificity were calculated. Summary receiver-operating characteristics (ROC) curves, assessing the diagnostic performance of both tests, were constructed. A subgroup analysis was performed to estimate the sensitivity and specificity of the various cut-off values. RESULTS: 13 studies were included. The ROC curves of the collected data illustrate that the LBC and L/S ratio perform equally well in the prediction of RDS. Comparison of the two summary ROC curves of each test indicates that the diagnostic performance of LBC might even have a slight advantage over L/S ratio. Due to the wide cut-off range it was not possible to define specific cut-off values with the best accuracy. CONCLUSION: We recommend replacing the L/S ratio as gold standard with the lamellar body count since the LBC is easy to perform, rapid, inexpensive, and available to all hospitals 24h per day.

Bewtra, M., L. M. Kaiser, et al. (2013). "Crohn's disease and ulcerative colitis are associated with elevated standardized mortality ratios: a meta-analysis." Inflamm Bowel Dis 19(3): 599-613.

BACKGROUND: : Evidence regarding all-cause and cause-specific mortality in inflammatory bowel disease (IBD) is conflicting, and debate exists over appropriate study design to examine these important outcomes. We conducted a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn's disease (CD) and ulcerative colitis (UC), and additionally examined various effects of study design on this outcome. METHODS: : A systematic search of PubMed and EMBASE was conducted to identify studies examining mortality rates relative to the general population. Pooled summary standardized mortality ratios (SMR) were calculated using random effect models. RESULTS: : Overall, 35 original articles fulfilled the inclusion and exclusion criteria, reporting all-cause mortality SMRs varying from 0.44 to 7.14 for UC and 0.71 to 3.20 for CD. The all-cause mortality summary SMR for inception cohort and population cohort UC studies was 1.19 (95% confidence interval, 1.06-1.35). The all-cause mortality summary SMR for inception cohort and population cohort CD studies was 1.38 (95% confidence interval, 1.23-1.55). Mortality from colorectal cancer, pulmonary disease, and nonalcoholic liver disease was increased, whereas mortality from cardiovascular disease was decreased. CONCLUSIONS: : Patients with UC and CD have higher rates of death from all causes, colorectal-cancer, pulmonary disease, and nonalcoholic liver disease.

Bhagat, S., M. Agarwal, et al. (2013). "Serratiopeptidase: A systematic review of the existing evidence." Int J Surg.

BACKGROUND: Serratiopeptidase is a proteolytic enzyme prescribed in various specialities like surgery, orthopaedics, otorhinolaryngology, gynaecology and dentistry for its anti-inflammatory, anti-edemic and analgesic effects. Some anecdotal reports suggest it to possess anti-atherosclerotic effects also, due to its fibrinolytic and caseinolytic properties. Despite being widely used there are few published studies regarding its efficacy. Thus, evidence regarding its clinical utility is needed. OBJECTIVE: To evaluate the existing evidence regarding efficacy and safety of Serratiopeptidase in clinical practice. EVIDENCE ACQUISITION: A systematic review of all the published articles of Serratiopeptidase using Cochrane Library, PubMed, MEDLINE, Clinical, Google, Dogpile and a manual search of bibliographies was conducted from 1st May 2011 till 15th July 2012. Further emails were sent to all the leading pharmaceuticals who are manufacturing this enzyme preparation for any additional information. All studies related to Serratiopeptidase which included Randomised controlled trials (RCTs), meta-analysis of RCTs, placebo-controlled, single-blind, double-blind, open label, prospective trials as well as preclinical studies were screened and analysed. The scientific credibility of the studies was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading checklist. A total of 24 studies on clinical efficacy of Serratiopeptidase met the inclusion criteria. EVIDENCE SYNTHESIS: Serratiopeptidase search on Cochrane library revealed 16 results among which 9 were Cochrane Central Register of Controlled Trials 2011, issue 4 studies and 7 were Cochrane Central Register of Controlled trials 2012, issue 3 studies. Of these 16 results, 11 were RCTs on efficacy of Serratiopeptidase. PubMed search also revealed 74 results which showed 16 Clinical trials, out of which 9 were RCTs related to Serratiopeptidase. Bandolier online edition (retrieved on 1/5/2011) showed a review 'Serratiopeptidase-finding the evidence' which included 9 RCTs. The evidence supporting the use of Serratiopeptidase as anti-inflammatory and analgesic agent is based on clinical studies which are of poor methodology. Only few RCTs, which are usually placebo control, with a small sample size are there. The dose and duration of treatment was not specified in some studies, and the outcome of the study was not clearly defined in a few. Data on the safety and tolerability of Serratiopeptidase is lacking in these studies. LIMITATIONS: A thorough search of literature was done to include all the relevant studies but we may have unknowingly missed a few of those studies which have not been published or registered with any of these search engines. The clinical evidence obtained have been graded according to the "Scottish Intercollegiate Grading Network" checklist by two separate reviewers and then coordinated together to give the final grading. Any disagreement between the two reviewers was resolved by discussion with the third reviewer. This was done to minimise bias but still the risk of bias cannot be completely ruled out. CONCLUSION: Serratiopeptidase is being used in many clinical specialities for its anti-inflammatory, anti-edemic and analgesic effects. It is even being promoted as a health supplement to prevent cardiovascular morbidity. The existing scientific evidence for Serratiopeptidase is insufficient to support its use as an analgesic and health supplement. The data on long-term safety of this enzyme is lacking. Evidence based recommendations on the analgesic, anti-atherosclerotic efficacy, safety and tolerability of Serratiopeptidase are needed.

Bhattacharjee, S., R. Bhattacharya, et al. (2013). "Antidepressant use and new-onset diabetes: a systematic review and meta-analysis." Diabetes Metab Res Rev.

BACKGROUND: Antidepressant use has been linked to new-onset diabetes. However, the existing literature on this relationship has yielded inconsistent findings. The primary objective of this study was to systematically synthesize the literature on the relationship between antidepressant use and new-onset diabetes using meta-analysis. METHODS: A systematic literature search was conducted to identify relevant studies in seven electronic databases. Two independent reviewers identified the final list of studies to be included in the meta-analysis using a priori selection criteria. Results for the primary outcome of interest, i.e., odds and hazards of developing new-onset diabetes, were pooled using a random-effects model. Egger's regression test and the Trim and Fill method were utilized to detect the presence of any potential publication bias. Sensitivity analysis was conducted using the leave-one-out method as well as individual categories of antidepressant drugs. RESULTS: Eight studies met the inclusion criteria. Random effects models revealed that adults with any use of antidepressants were more likely to develop new-onset diabetes compared to those without any use of antidepressants (OR = 1.50, 95% CI 1.08-2.10; HR = 1.19, 95% CI 1.08-1.32). Sensitivity analyses revealed fair robustness. SSRIs and TCAs were more likely to be associated with the development of new-onset diabetes. Results from the Egger's regression test and Trim and Fill method revealed no evidence of publication bias. CONCLUSIONS: Among adults, antidepressant use was associated with higher chances of new-onset diabetes. However, since a cause-and-effect relationship cannot be established by observational studies, future randomized controlled studies are needed to confirm this association. Copyright (c) 2013 John Wiley & Sons, Ltd.

Biancari, F., V. D'Andrea, et al. (2013). "Current Treatment and Outcome of Esophageal Perforations in Adults: Systematic Review and Meta-Analysis of 75 Studies." World J Surg.

BACKGROUND: The current prognosis of esophageal perforation and the efficacy of available treatment methods are not well defined. METHODS: We performed a systematic review of esophageal perforations published from January 2000 to April 2012 and subjected a proportion of the retrieved data to a meta-analysis. Meta-regression was performed to determine predictors of mortality immediately after esophageal perforation. RESULTS: Analysis of 75 studies resulted in a pooled mortality of 11.9 % [95 % confidence interval (CI) 9.7-14.3: 75 studies with 2,971 patients] with a mean hospital stay of 32.9 days (95 % CI 16.9-48.9: 28 studies with 1,233 patients). Cervical perforations had a pooled mortality of 5.9 %, thoracic perforations 10.9 %, and intraabdominal perforations 13.2 %. Mortality after esophageal perforation secondary to foreign bodies was 2.1 %, iatrogenic perforation 13.2 %, and spontaneous perforation 14.8 %. Treatment started within 24 h after the event resulted in a mortality rate of 7.4 % compared with 20.3 % in patients treated later (risk ratio 2.279, 95 % CI 1.632-3.182). Primary repair was associated with a pooled mortality of 9.5 %, esophagectomy 13.8 %, T-tube or any other tube repair 20.0 %, and stent-grafting 7.3 %. CONCLUSIONS: Results of recent studies indicate that mortality after esophageal perforation is high despite any definitive surgical or conservative strategy. Stent-grafting is associated with somewhat lower mortality rates, but studies may be biased by patient selection and limited experience.

Bianco, A., B. Quaresima, et al. (2013). "Polymorphic Repeat Length in the AIB1 Gene and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Meta-Analysis of Observational Studies." PLoS One 8(3): e57781.

We carried out a meta-analysis focusing on the relationship between length of AIB1 gene poly-Q repeat domain as a modifier of breast cancer (BC) susceptibility in patients with BRCA1 and BRCA2 mutation carriers. We searched MEDLINE and EMBASE for all medical literature published until February, 2012. Studies were included in the meta-analysis if they met all the predetermined criteria, such as: (a) case-control or cohort studies; (b) the primary outcome was clearly defined as BC; (c) the exposure of interest measured was AIB1 polyglutamine repeat length genotype; (d) provided relative risk (RR) or odds ratio (OR) estimates and their 95% confidence intervals (CIs). Two of the authors independently evaluated the quality of the studies included and extracted the data. Meta-analyses were performed for case-control and cohort studies separately. Heterogeneity was examined and the publication bias was assessed with a funnel plot for asymmetry. 7 studies met our predetermined inclusion criteria and were included in the meta-analysis. Overall quality ratings of the studies varied from 0.36 to 0.77, with a median of 0.5. The overall RR estimates of 29/29 poly-Q repeats on risk of BC in BRCA1/2, BRCA1, and BRCA2, were always greater than 1.00; however, this effect was not statistically significant. In the meta-analysis of studies reporting the effect of 28/28 poly-Q repeats on risk of BC in BRCA1/2, BRCA1, and BRCA2, the overall RR decreased below 1.00; however, this effect was not statistically significant. Similar estimates were shown for at least 1 allele of </=26 repeats. Genotypes of AIB1 polyglutamine polymorphism analyzed do not appear to be associated to a modified risk of BC development in BRCA1 and BRCA2 mutation carriers. Future research on length of poly-Q repeat domain and BC susceptibility should be discouraged and more promising potential sources of penetrance variation among BRCA1 and BRCA2 mutation carriers should be investigated.

Biasin, M., M. Sironi, et al. (2013). "Endoplasmic reticulum aminopeptidase 2 (ERAP2) haplotypes play a role in modulating susceptibility to HIV infection." AIDS.

OBJECTIVE:: Haplotype-specific alternative splicing of the endoplasmic reticulum aminopeptidase type 2 (ERAP2) gene results in either full-length (FL, haplotype A) or alternatively spliced (AS, haplotype B) mRNA. As ERAP2 trims peptides loaded on MHC class I and CD8+ T lymphocytes protect against viral infections, we analysed its role in resistance to HIV-1 infection. METHODS:: ERAP2 polymorphisms were genotyped using a TaqMan probe, HLA typing of class-I HLAB locus was performed by SSP-PCR method. To verify if ERAP2 genotype influences susceptibility to HIV-1 infection in vitro we performed HIV-1 infection assay. We evaluated antigen presentation pathway with PCR array and the viral antigen p24 with ELISA. RESULTS:: Genotype analysis in 104 HESN exposed to HIV through injection drug use (IDU-HESN) and 130 controls from Spain indicated that hapA protects from HIV infection. Meta-analysis with an Italian cohort of sexually-exposed HESN yielded a p value of 7.6 x10. HLAB typing indicated that the HLA-B*57 allele is significantly more common than expected among HESN homozygous for haplotype A (homoA). Data obtained in a cohort of 139 healthy Italian controls showed that following in vitro HIV-1 infection the expression of ERAP2-FL and a number of genes involved in antigen presentation as well as of MHC class I on the surface of CD45+ cells was significantly increased in homoA cells; notably, homoA PBMC, but not isolated CD4+ cells, were less susceptible to HIV-1 infection. CONCLUSION:: ERAP2 hapA is correlated with resistance to HIV-1 infection, possibly secondarily to its effect on antigen processing and presentation.

Biemans, J. M. and M. R. van Balken (2013). "Efficacy and effectiveness of percutaneous tibial nerve stimulation in the treatment of pelvic organ disorders: a systematic review." Neuromodulation 16(1): 25-34.

Objective: This systematic review aimed to determine the efficacy and effectiveness of percutaneous tibial nerve stimulation (PTNS) on symptoms of overactive bladder (OAB) and pelvic organ disorders, pain, adverse events (AEs), and quality of life (QoL). Methods: A literature search was performed in September 2011 in the databases MEDLINE, CINAHL, and EMBASE. Hand searching of references was conducted. Only randomized controlled trials (RCTs) and controlled clinical trials (CCTs) with adult patients were included. Results: Seven studies met the eligibility criteria. Five RCTs indicated improvement (range 36.7-80%) on OAB symptoms, frequency, urgency, nocturia, and incontinence. One CCT reported improvement (mean 15.7) in 53% of the subjects on fecal incontinence (FI) symptoms on an FI Questionnaire (range 0-20). One RCT showed more than 50% improvement on pain (40%) and symptom scores (66.6%) in chronic pelvic pain (CPP). Limitations are the small amount, overall low quality, and variety in outcome measures of included studies. Only minor AEs were reported. No meta-analysis was performed as a consequence of heterogeneous data. Conclusions: This systematic review provides evidence for the efficacy of PTNS on symptoms, pain, and QoL measures of OAB, FI and category IIIB CP/CPP. Evidence of effectiveness was found on symptoms and QoL for OAB. The total amount of seven included studies, from which even the most favorable study has some potential bias, is too small to draw firm conclusions. Independent high quality RCTs are necessary to confirm and delineate the range of therapeutic effects of PTNS in this region. PTNS is a safe intervention.

Bignami, E., T. Greco, et al. (2013). "The effect of isoflurane on survival and myocardial infarction: a meta-analysis of randomized controlled studies." J Cardiothorac Vasc Anesth 27(1): 50-8.

OBJECTIVE: The aim of this meta-analysis was to investigate the cardioprotective properties of isoflurane versus any comparator in terms of the rate of myocardial infarction and all-cause mortality. DESIGN: Pertinent studies were searched independently in Biomed, Central, PubMed, Embase, and the Cochrane Central Register of clinical trials. The primary endpoint was mortality at the longest follow-up available. SETTING: A hospital. PARTICIPANTS: Randomized controlled trials. INTERVENTION: A meta-analysis of 37 trials. MEASUREMENTS AND MAIN RESULTS: The 37 included trials randomized 3,539 patients in cardiac (16 studies) and in noncardiac surgery (21 studies) with noninhalation comparators in 55% of trials. The overall analysis showed no difference in mortality between the isoflurane and control groups (16/1,602 [1.0%] v 23/1,937 [1.2%], odds ratios (OR) = 0.76 [0.39-1.47], p = 0.4 with 37 studies included) and no difference in the rate of myocardial infarction (3/1,312 [0.2%] v 1/1,532 [0.07%], OR = 2.03 [0.27-15.49], p = 0.5 with 30 studies included). Mortality was reduced in the isoflurane group when only studies with a low risk of bias were included in the analyses (0/540 [0%] v 5/703 [0.7%] in the control arm, OR = 0.13 [0.02-0.76], p = 0.02) with 4 cardiac and 6 noncardiac trials included and 5 noninhalation and 5 inhalation agents as the comparator. A trend was noted when a subanalysis was performed with propofol as a comparator (1/544 [0.2%] v 6/546 [1.1%], p = 0.05, with 16 studies included). CONCLUSIONS: Isoflurane reduced mortality in high-quality studies and showed a trend toward a reduction in mortality when it was compared with propofol. No differences in the rates of overall mortality and myocardial infarction were noted.

Bin, Q. and J. Luo (2013). "Role of polymorphisms of GSTM1, GSTT1 and GSTP1 Ile105Val in Hodgkin and non-Hodgkin lymphoma risk: a Human Genome Epidemiology (HuGE) review." Leuk Lymphoma 54(1): 14-20.

Glutathione S-transferases (GSTs) are postulated to be involved in the detoxification of potential carcinogens, and gene variation may alter susceptibility to lymphomas. Results from several previous epidemiologic studies have been inconsistent. Hence a meta-analysis was conducted to verify the role of GST genetic polymorphisms in lymphoma risk. Eleven trials involving 1626 patients and 2892 controls were analyzed. Pooled results showed that the GSTT1 null polymorphism might increase the risk of lymphoma (odds ratio [OR] 2.26, 95% confidence interval [CI] 1.20, 4.24; p = 0.01; random-effects model), whereas the impact of GSTM1 and GSTP1 Ile105Val polymorphisms was not significant. Subgroup analysis showed the GSTT1 null genotype to be a risk factor for non-Hodgkin lymphoma (NHL) (OR 2.75, 95% CI 1.17, 6.45; p = 0.02; random-effects model) but not for Hodgkin lymphoma (HL), and the effect remained evident in females (OR 1.43, 95% CI 1.04, 1.97; p = 0.03; I(2) = 41.0%, p for heterogeneity = 0.15; fixed-effects model). An effect of GSTM1 and GSTT1 double null genotype on lymphoma risk was also shown (OR 2.09, 95% CI 1.31, 3.33; p = 0.01; random-effects model). In conclusion, the GSTT1 null genotype appears to be associated with a modest increase in the risk of NHL, whereas the GSTM1 and GSTP1 Ile105Val polymorphisms are unrelated to lymphoma risk.

Biondi-Zoccai, G., G. Sangiorgi, et al. (2013). "Drug-eluting balloons for peripheral artery disease: A meta-analysis of 7 randomized clinical trials and 643 patients." Int J Cardiol.

Biron, K. E., D. L. Dickstein, et al. (2013). "Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization." Sci Rep 3: 1354.

Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (Abeta) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. Abeta immunotherapy is an experimental treatment for AD; however, unexpected negative vascular side effects seen in early human clinical trials demonstrate that our knowledge of Abeta and AD pathogenesis is incomplete. We demonstrate that immunization with Abeta peptides neutralizes the amyloid trigger leading to neoangiogenesis and reverses hypervascularity in Tg2576 AD mice. This process resolves plaque burden suggesting that neoangiogenesis is a key mechanism underlying plaque formation. A meta-analysis demonstrated that hypervascular reversion in vaccinated Alzheimer's patients. This appears to be the first example of vascular reversion following any therapeutic intervention and supports the conclusion that modulation of neoangiogenesis may repair damage in the AD brain.

Blanco, M., C. Jurie, et al. (2013). "Impact of animal and management factors on collagen characteristics in beef: a meta-analysis approach." Animal: 1-11.

The aim of this paper was to identify pre-slaughter factors that modify total and insoluble collagen contents in bovine muscle to construct a model of collagen dynamics. The meta-analyses were performed with primary data of total (n = 1165) and insoluble (n = 1145) collagen contents from INRA experiments obtained from different muscles in young bulls, cows and steers. According to both the bibliography and meta-analyses, total collagen content and solubility were greatly affected by the muscle (type). Moreover, the pattern of the evolution of collagen characteristics was similar among Longissimus, Semitendinosus and Triceps brachii muscles in young bulls. In cows, collagen contents in the Triceps brachii muscle had delayed dynamics compared with the other muscles. Collagen characteristics differed among breeds because of variation in the maturity of the breed. Similarly, according to the meta-analyses, total and insoluble collagen content evolutions with the degree of maturity (DOM; proportion of adult weight reached at slaughter) were different in dairy and rustic breeds from those of beef breeds, especially in bulls. Although the relationships between collagen content and DOM were quantified in different muscles and sexes, the precision of the fitted equations was not sufficient for prediction. Consequently, relying on the hypotheses raised by the meta-analysis and the literature, an approach to further develop a dynamic mechanistic model of soluble and insoluble collagen content is proposed.

Blikman, L. J., B. M. Huisstede, et al. (2013). "Effectiveness of Energy-Conservation treatment in reducing fatigue in Multiple Sclerosis: a systematic review and meta-analysis." Arch Phys Med Rehabil.

OBJECTIVES: To systematically review the effects of Energy-Conservation-Management (ECM)-treatment for fatigue in MS. We also studied the effect of ECM-treatment on restrictions in participation and quality of life (QoL). DATA SOURCES: PubMed, CINAHL, EMBASE and Web Of Knowledge were searched to identify relevant RCTs and CCTs. STUDY SELECTION: To select potential studies, two reviewers independently applied the inclusion criteria. DATA EXTRACTION: Two reviewers independently extracted data and assessed the methodological quality of the studies included. If meta-analysis was not possible, qualitative best-evidence synthesis was used to summarize the results. DATA SYNTHESIS: The searches identified 532 studies, 6 of which were included. The studies compared the short-term effects of ECM-treatment and control treatment on fatigue and QoL; one study reported short- and mid-term effects on participation, but found no evidence for effectiveness. Meta-analyses (2 RCTs, N=350) showed that ECM-treatment was more effective than no treatment in improving subscale scores of the I) FIS (Fatigue Impact Scale): cognitive (pooled MD, -2.91; 95% CI, -4.32 to -1.50), physical (-2.99; -4.47 to -1.52) and psychosocial (-6.05; -8.72 to -3.37); and II) QoL: role physical (17.26; 9.69-24.84), social function (6.91; 1.32-12.49) and mental health (5.55; 2.27-8.83). Limited or no evidence was found for the effectiveness of ECM-treatment on the other outcomes in the short- or mid-term. None of the studies reported long-term results. CONCLUSIONS: The systematic review results provide evidence that, in the short-term, ECM-treatment can be more effective than no treatment (waiting controls) in reducing the impact of fatigue and in improving three QoL scales: role physical, social function and mental health in fatigued MS patients. More RCTs that also study long-term results are needed.

Blomberg, B. A., M. C. Moghbel, et al. (2013). "The value of radiologic interventions and (18)F-DOPA PET in diagnosing and localizing focal congenital hyperinsulinism: systematic review and meta-analysis." Mol Imaging Biol 15(1): 97-105.

PURPOSE: This systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium stimulation with hepatic venous sampling (ASVS), and (18)F-DOPA positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). PROCEDURES: This systematic review and meta-analysis was conducted according to the PRISMA statement. PubMed, EMBASE, SCOPUS and Web of Science electronic databases were systematically searched from their inception to November 1, 2011. Using predefined inclusion and exclusion criteria, two blinded reviewers selected articles. Critical appraisal ranked the retrieved articles according to relevance and validity by means of the QUADAS-2 criteria. Pooled data of homogeneous study results estimated the sensitivity, specificity, likelihood ratios and diagnostic odds ratio (DOR). RESULTS: (18)F-DOPA PET was superior in distinguishing focal from diffuse CHI (summary DOR, 73.2) compared to PVS (summary DOR, 23.5) and ASVS (summary DOR, 4.3). Furthermore, it localized focal CHI in the pancreas more accurately than PVS and ASVS (pooled accuracy, 0.82 vs. 0.76, and 0.64, respectively). Important limitations comprised the inclusion of studies with small sample sizes, high probability of bias and heterogeneity among their results. Studies with small sample sizes and high probability of bias tended to overestimate the diagnostic accuracy. CONCLUSIONS: This systematic review and meta-analysis found evidence for the superiority of (18)F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery for this disease.

Blumfield, M. L., A. J. Hure, et al. (2013). "A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries." Nutr Rev 71(2): 118-32.

Micronutrient status during pregnancy influences maternal and fetal health, birth outcomes, and the risk of chronic disease in offspring. Research reporting dietary intake during pregnancy in nationally representative population samples, however, is limited. This review summarizes the micronutrient intakes of pregnant women from developed countries and compares them with relevant national recommendations. A systematic search without date limits was conducted. All studies reporting the micronutrient intakes of pregnant women were considered, irrespective of design. Two authors independently identified studies for inclusion and assessed methodological quality. Nutritional adequacy was summarized, with confounding factors considered. Meta-analysis data are reported for developed countries collectively, by geographical region, and by dietary methodology. Pregnant women in developed countries are at risk of suboptimal micronutrient intakes. Folate, iron, and vitamin D intakes were consistently below nutrient recommendations in each geographical region, and calcium intakes in Japan were below the Japanese recommendations and the average intake levels in other developed countries. Research examining the implications of potential nutrient insufficiency on maternal and offspring health outcomes is needed along with improvements in the quality of dietary intake reporting.

Bodalia, P. N., A. M. Grosso, et al. (2013). "Comparative Efficacy and Tolerability of Antiepileptic Drugs for Refractory Focal Epilepsy Systematic Review and Network Meta-Analysis reveals the need for long-term comparator trials." Br J Clin Pharmacol.

To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of antiepileptic drugs (AEDs) for refractory epilepsy. METHODS: We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group's specialised register; MEDLINE (1950 to March 2009); EMBASE (1980 to March 2009); and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis. RESULTS: Forty-two eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only two direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio [OR] 3.78 [95% CI 3.14 to 4.55]) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritised oxcarbazepine, topiramate and pregabalin on the basis of short-term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritised on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognised as being associated with serious visual disturbance with chronic use. CONCLUSION: Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam, and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active-comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters.

Bodis-Wollner, I. (2013). "Foveal vision is impaired in Parkinson's disease." Parkinsonism Relat Disord 19(1): 1-14.

PURPOSE: The article aims to review foveal involvement in Parkinson's disease. SCOPE: Clinical observations as well as electrophysiological and anatomical studies in animal models provide evidence that Parkinson's disease (PD) affects vision. The retina is the most distal locus of visual dysfunction in PD as shown by electroretinographic (ERG) and optical coherence tomographic (OCT) studies. Thinning of the retinal nerve fibre layer (RNFL) and the fovea has been reported in PD. This review summarises retinal physiology and foveal visual dysfunction in PD and quantification of retinal thinning as reported in different studies and using different instruments. At this point due to methodological diversity and relatively low number of subjects studied, a meta-analysis is not yet possible. Results obtained on one equipment are not yet transferable to another. The author also briefly alludes to some links of visual processing deficits beyond visual detection, such as visual discrimination, visual categorisation and visuospatial orientation in PD. CONCLUSIONS: There are some promising results suggesting the potential applicability of ST-Oct as a biomarker in PD. Furthermore, these data raise some interesting neurobiological questions. However, there are identifiable pitfalls before OCT quantification may be used as a biomarker in PD. Analysis standardisation is needed on a larger than existing healthy and patient population. Furthermore, longitudinal studies are needed. The exact relationship between retinal foveal deficits and visuo-cognitive impairment in PD remains a challenging research question.

Boer, D. and R. Fischer (2013). "How and When Do Personal Values Guide Our Attitudes and Sociality? Explaining Cross-Cultural Variability in Attitude-Value Linkages." Psychol Bull.

This article examines how and when personal values relate to social attitudes. Considering values as motivational orientations, we propose an attitude-value taxonomy based on Moral Foundation Theory (Haidt & Joseph, 2007) and Schwartz's (1992) basic human values theory allowing predictions of (a) how social attitudes are related to personal values, and (b) when macro-contextual factors have an impact on attitude-value links. In a meta-analysis based on the Schwartz Value Survey (Schwartz, 1992) and the Portrait Value Questionnaire (Schwartz et al., 2001; k = 91, N = 30,357 from 31 countries), we found that self-transcendence (vs. self-enhancement) values relate positively to fairness/proenvironmental and care/prosocial attitudes, and conservation (vs. openness-to-change) values relate to purity/religious and authority/political attitudes, whereas ingroup/identity attitudes are not consistently associated with value dimensions. Additionally, we hypothesize that the ecological, economic, and cultural context moderates the extent to which values guide social attitudes. Results of the multi-level meta-analysis show that ecological and cultural factors inhibit or foster attitude-value associations: Disease stress is associated with lower attitude-value associations for conservation (vs. openness-to-change) values; collectivism is associated with stronger attitude-value links for conservation values; individualism is associated with stronger attitude-value links for self-transcendence (vs. self-enhancement) values; and uncertainty avoidance is associated with stronger attitude-values links, particularly for conservation values. These findings challenge universalistic claims about context-independent attitude-value relations and contribute to refined future value and social attitude theories. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Boers, M., L. van Tuyl, et al. (2013). "Meta-analysis suggests that intensive non-biological combination therapy with step-down prednisolone (COBRA strategy) may also 'disconnect' disease activity and damage in rheumatoid arthritis." Ann Rheum Dis 72(3): 406-9.

BACKGROUND/OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF) antagonists changes the relationship between disease activity and progression of radiological joint damage ('disconnect'): patients who have little or no response of disease activity still show reductions in damage progression. In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine with step-down prednisolone) has been shown to be equivalent to high-dose methotrexate and infliximab in suppressing damage progression (BeSt trial). We investigated whether COBRA treatment can also 'disconnect' disease activity and damage. DESIGN: A meta-analysis combined data from the COBRA trial (COBRA vs sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs sequential monotherapy). Linear regression related 1-year progression of damage (Sharp van der Heijde score) as a dependent variable with disease activity (time-averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein (CRP)), treatment strategy (COBRA or control) and their interaction (indicator of a disconnect) as independent variables. The main outcome was the pooled interaction term. RESULTS: Complete data from 60-100% of patients were available. Before pooling, disease activity was the only (strongly) significant independent factor related to damage progression. The pooled interaction term was (weakly) significant: time-averaged DAS44xtreatment interaction, one-sided p=0.027; time-averaged CRPxtreatment interaction, one-sided p=0.044. CONCLUSIONS: Changes in the relationship between disease activity and damage progression may not be limited to anti-TNF treatment, but a property of early, rapid and deep suppression of joint inflammation, also induced by conventional strategies that include glucocorticoids.

Bohrer, B. M., J. M. Kyle, et al. (2013). "Meta-analysis of the effects of ractopamine hydrochloride on carcass cutability and primal yields of finishing pigs." J Anim Sci 91(2): 1015-1023.

The objective was to summarize previous literature, using a meta-analysis approach, on the effects of ractopamine hydrochloride (RAC) when fed at doses of 5 to 10 mg/kg for up to 35 d before harvest on carcass cutability and belly quality of finishing pigs. The meta-analysis provided an opportunity to determine the consensus of previously published literature. Ten studies were evaluated to determine cutting yields and 8 studies were used to determine belly quality in this review. Pooled dietary RAC concentrations (5 mg/kg, 7.4 mg/kg, 10 mg/kg, and step-up feeding programs) and pooled feeding durations (up to 35 d before harvest) were compared with pigs not fed RAC (controls) and were analyzed as a meta-analysis using the mixed procedure of SAS. Ractopamine inclusion was the fixed effect in the model and the individual study was considered a random variable. The only difference between RAC and control pigs for whole primals as a percentage of side weight was the whole ham (P < 0.01). No other differences were detected for whole primals as a percentage of side weight. Yet, differences were detected in the standardized trimmed primal yields. A difference (P < 0.05) in percentages of the side weight was detected for the Boston butt, trimmed loin, and trimmed ham. This translated into RAC pigs having a carcass cutting yield (74.70% vs. 73.69%, respectively; P = 0.02; SED = 0.33) advantage of 1.01% units and a bone in lean cutting yield (61.43% vs. 60.33%, respectively; P = 0.03; SED = 0.40) advantage of 1.10% units when compared with control pigs. The advantage in bone-in cutability was a result of increased boneless sub primal yields in each of the lean cuts (shoulder, loin, and ham). When further evaluated, RAC pigs had a boneless shoulder (Boston butt + picnic) yield advantage of 0.32% units (P < 0.01; SED = 0.11), a 0.43% unit (P = 0.01; SED = 0.13) yield advantage in the boneless loin (Canadian back + tenderloin + sirloin), and a 0.51% unit (P < 0.001; SED = 0.11) advantage in the boneless ham (inside + outside + knuckle). A boneless yield was calculated using a summation of the percentage of side weight from the boneless shoulder, boneless loin, and boneless ham, which resulted in a 1.08% unit (36.28% vs. 35.20%, respectively; P = 0.002; SED = 0.25) advantage of RAC pigs when compared with control pigs. There were no subprimal yield differences (P = 0.93) in the trimmed belly between RAC pigs (12.18%) and control pigs (12.18%). However, RAC pigs (15.27 cm; 73.42) had narrower flop distances (P = 0.02; SED = 0.62) and greater iodine values (P = 0.01; SED = 0.33), respectively, when compared with control pigs (17.08 cm; 71.48).

Boillot, A., S. Zoungas, et al. (2013). "Obesity and the microvasculature: a systematic review and meta-analysis." PLoS One 8(2): e52708.

BACKGROUND: Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber. METHODS AND FINDINGS: Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 mum [95% CI: -0.08; -0.06] in arteriolar caliber and 0.22 mum [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children. CONCLUSIONS: Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists.

Boland, M. R., A. Noorani, et al. (2013). "Perioperative Fluid Restriction in Major Abdominal Surgery: Systematic Review and Meta-analysis of Randomized, Clinical Trials." World J Surg.

BACKGROUND: Fluid management is a fundamental component of surgical care. Recently, there has been considerable interest in perioperative fluid restriction as a method of facilitating recovery following elective major surgery. A number of randomized trials have addressed the issue in various surgical specialities, and a recent meta-analysis proposed uniform definitions regarding fluid amount as well as examining fluid restriction in patients undergoing colonic resection. METHODS: Medline, Embase, trial registries, conference proceedings, and article reference lists were searched to identify randomized, controlled trials of perioperative fluid restriction versus "standard" perioperative fluid management, as per definitions formulated previously. All of the studies involved patients undergoing colonic resection. The primary outcome measure was postoperative morbidity. Secondary endpoints included mortality, renal failure, time to first flatus, and length of hospital stay. A random effects model was applied. RESULTS: Seven randomized, controlled trials with a total of 856 patients investigating standard versus restrictive fluid regimes, as denoted by the definitions, were included. Perioperative fluid restriction had no effect on the risk of postoperative complications (OR 0.49 (95 % confidence interval (CI) 0.2-1.18; P = 0.101). There was no detectable effect on death and fluid restriction did not reduce hospital stay (Pooled weighted mean difference -0.25; 95 % CI 0.72-0.21; P = 0.29). CONCLUSIONS: Perioperative fluid restriction does not significantly reduce the risk of complications following major abdominal surgery. Furthermore, it does not appear to reduce length of hospital stay.

Bolier, L., M. Haverman, et al. (2013). "Positive psychology interventions: a meta-analysis of randomized controlled studies." BMC Public Health 13(1): 119.

ABSTRACT: BACKGROUND: The use of positive psychological interventions may be considered as a complementary strategy in mental health promotion and treatment. The present article constitutes a meta-analytical study of the effectiveness of positive psychology interventions for the general public and for individuals with specific psychosocial problems. METHODS: We conducted a systematic literature search using PubMed, PsychInfo, the Cochrane register, and manual searches. Forty articles, describing 39 studies, totaling 6,139 participants, met the criteria for inclusion. The outcome measures used were subjective well-being, psychological well-being and depression. Positive psychology interventions included self-help interventions, group training and individual therapy. RESULTS: The standardized mean difference was 0.34 for subjective well-being, 0.20 for psychological well-being and 0.23 for depression indicating small effects for positive psychology interventions. At follow-up from three to six months, effect sizes are small, but still significant for subjective well-being and psychological well-being, indicating that effects are fairly sustainable. Heterogeneity was rather high, due to the wide diversity of the studies included. Several variables moderated the impact on depression: Interventions were more effective if they were of longer duration, if recruitment was conducted via referral or hospital, if interventions were delivered to people with certain psychosocial problems and on an individual basis, and if the study design was of low quality. Moreover, indications for publication bias were found, and the quality of the studies varied considerably. CONCLUSIONS: The results of this meta-analysis show that positive psychology interventions can be effective in the enhancement of subjective well-being and psychological well-being, as well as in helping to reduce depressive symptoms. Additional high-quality peer-reviewed studies in diverse (clinical) populations are needed to strengthen the evidence-base for positive psychology interventions.

Bollen, A. M. (2013). "Self-Etching Primers Result in Higher Odds of Attachment Failure Than Acid Etch, but Do Result in Modest Time Savings." J Evid Based Dent Pract 13(1): 18-19.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Self-etch primers and conventional acid-etch technique for orthodontic bonding: a systematic review and meta-analysis. Fleming PS, Johal A, Pandis N. Am J Orthod Dentofacial Orthop 2012;142:83-94. REVIEWER: Anne-Marie Bollen, DDS, MS, PhD PURPOSE/QUESTION: To assess the risk of attachment failure, bonding time, and demineralization adjacent to attachments between 1-stage (self-etch) and 2-stage (acid etch) bonding in orthodontic patients over a minimum follow-up period of 12 months SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Systematic review and meta-analysis LEVEL OF EVIDENCE: Level 1: Good-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade A: Consistent, good-quality patient-oriented evidence.

Bollhalder, L., A. M. Pfeil, et al. (2013). "A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation." Clin Nutr 32(2): 213-23.

BACKGROUND & AIMS: Glutamine supplementation has been associated with reduced mortality, infections and hospital length of stay in critically ill patients and patients undergoing major surgery. We carried out a meta-analysis to examine randomized clinical trial (RCT)-based evidence of these effects. METHODS: Based on a systematic database search, RCTs published since 1990 were included if they evaluated the effect of parenteral glutamine supplementation against a background of parenteral nutrition. Enteral (tube) feeding in a proportion of patients was allowable. Information on RCT methodology, quality and outcomes was extracted. Random effects meta-analysis followed the DerSimonian-Laird approach. RESULTS: Forty RCTs were eligible for meta-analysis. Parenteral glutamine supplementation was associated with a non-significant 11% reduction in short-term mortality (RR = 0.89; 95% CI, 0.77-1.04). Infections were significantly reduced (RR = 0.83; 95% CI, 0.72-0.95) and length of stay was 2.35 days shorter (95% CI, -3.68 to -1.02) in the glutamine arms. Meta-analysis results were strongly influenced by one recent trial. An element of publication bias could not be excluded. CONCLUSION: Parenteral glutamine supplementation in severely ill patients may reduce infections, length of stay and mortality, but substantial uncertainty remains. Unlike previous meta-analyses, we could not demonstrate a significant reduction in mortality.

Bonequi, P., F. Meneses-Gonzalez, et al. (2013). "Risk factors for gastric cancer in Latin America: a meta-analysis." Cancer Causes Control 24(2): 217-31.

BACKGROUND: Latin America has among the highest gastric cancer incidence rates in the world, for reasons that are still unknown. In order to identify region-specific risk factors for gastric cancer, we conducted a meta-analysis summarizing published literature. METHODS: Searches of PubMed and regional databases for relevant studies published up to December 2011 yielded a total of 29 independent case-control studies. We calculated summary odds ratios (OR) for risk factors reported in at least five studies, including socioeconomic status (education), lifestyle habits (smoking and alcohol use), dietary factors (consumption of fruits, total vegetables, green vegetables, chili pepper, total meat, processed meat, red meat, fish, and salt), and host genetic variants (IL1B-511T, IL1B-31C, IL1RN*2, TNFA-308A, TP53 codon 72 Arg, and GSTM1 null). Study-specific ORs were extracted and summarized using random-effects models. RESULTS: Chili pepper was the only region-specific factor reported in at least five studies. Consistent with multifactorial pathogenesis, smoking, alcohol use, high consumption of red meat or processed meat, excessive salt intake, and carriage of IL1RN*2 were each associated with a moderate increase in gastric cancer risk. Conversely, higher levels of education, fruit consumption, and total vegetable consumption were each associated with a moderately decreased risk. The other exposures were not significantly associated. No prospective study data were identified. CONCLUSION: Risk factor associations for gastric cancer in Latin America are based on case-control comparisons that have uncertain reliability, particularly with regard to diet; the specific factors identified and their magnitudes of association are largely similar to those globally recognized. Future studies should emphasize prospective data collection and focus on region-specific exposures that may explain high gastric cancer risk.

Bonifazi, M., I. Tramacere, et al. (2013). "Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies." Rheumatology (Oxford) 52(1): 143-54.

OBJECTIVES: A higher incidence of cancer in scleroderma patients compared with the general population has been suggested by several observational studies, reporting, however, different estimates. Therefore, we aimed to perform a systematic review and meta-analysis to definitely assess this association. METHODS: We searched MEDLINE and Embase for all original articles of observational studies on cancer incidence in scleroderma patients without language restriction published up to December 2011. Two independent authors reviewed all titles/abstracts and retrieved detailed full-text of potentially relevant articles to identify studies according to predefined selection criteria. Summary estimates were derived using random-effects model and reported as relative risk (RR). Publication bias was evaluated by trim and fill analysis. RESULTS: From articles initially identified, 16 original studies, involving more than 7000 patients, were included in the present review. Compared with the general population, the summary RR to develop all invasive cancers in scleroderma patients was 1.75 (95% CI 1.41, 2.18). The results for selected cancer sites indicated a strong association with lung cancer (RR 4.35; 95% CI 2.08, 9.09), and a significant increased risk also for haematological neoplasms (RR 2.24; 95% CI 1.53, 3.29). The relation with breast cancer, suggested in some previous epidemiological studies, was not confirmed (RR 1.05; 95% CI 0.86, 1.29). CONCLUSION: The present meta-analysis, the first on scleroderma and cancer risk, provides definite estimates on the association between scleroderma and cancer.

Bonzi, M., E. M. Fiorelli, et al. (2013). "Head-up tilt testing for diagnosing vasovagal syncope: A meta-analysis." Int J Cardiol.

Boonekamp, J. J., M. J. Simons, et al. (2013). "Telomere length behaves as biomarker of somatic redundancy rather than biological age." Aging Cell.

Biomarkers of aging are essential to predict mortality and aging-related diseases. Paradoxically, age itself imposes a limitation on the use of known biomarkers of aging because their associations with mortality generally diminish with age. How this pattern arises is, however, not understood. With meta-analysis we show that human leucocyte telomere length (TL) predicts mortality, and that this mortality association diminishes with age, as found for other biomarkers of aging. Subsequently, we demonstrate with simulation models that this observation cannot be reconciled with the popular hypothesis that TL is proportional to biological age. Using the reliability theory of aging, we instead propose that TL is a biomarker of somatic redundancy, the body's capacity to absorb damage, which fits the observed pattern well. We discuss to what extent diminishing redundancy with age may also explain the observed diminishing mortality modulation with age of other biomarkers of aging. Considering diminishing somatic redundancy as the causal agent of aging may critically advance our understanding of the aging process, and improve predictions of life expectancy and vulnerability to aging-related diseases.

Bora, E. and C. Pantelis (2013). "Theory of mind impairments in first-episode psychosis, individuals at ultra-high risk for psychosis and in first-degree relatives of schizophrenia: Systematic review and meta-analysis." Schizophr Res 144(1-3): 31-6.

Theory of mind (ToM) deficit is a well-established feature of schizophrenia and has been suggested as a vulnerability marker of this disorder. However, as most of this evidence is based on studies in chronic patients, it is less clear whether ToM is impaired prior to or following the onset of a first-episode and whether it is evident in unaffected relatives of patients. In this meta-analysis, ToM performance of 3005 individuals with first-episode psychosis (FEP), individuals at ultra-high risk for psychosis (UHR) and unaffected relatives were compared with 1351 healthy controls. ToM was substantially impaired in first-episode psychosis (Cohen d=1.0) and this deficit was comparable to findings in chronic patients. ToM was also impaired in unaffected relatives (d=0.37) and UHR subjects (d=0.45) and performances of these groups were intermediate between FES and healthy controls. Severity of ToM deficits in unaffected relatives and UHR subjects was similar to other cognitive deficits observed in these groups. Longitudinal studies of clinical and genetic high-risk subjects are necessary to investigate the trajectory of development of ToM deficits in schizophrenia.

Borenstein, M. and J. P. Higgins (2013). "Meta-Analysis and Subgroups." Prev Sci.

Subgroup analysis is the process of comparing a treatment effect for two or more variants of an intervention-to ask, for example, if an intervention's impact is affected by the setting (school versus community), by the delivery agent (outside facilitator versus regular classroom teacher), by the quality of delivery, or if the long-term effect differs from the short-term effect. While large-scale studies often employ subgroup analyses, these analyses cannot generally be performed for small-scale studies, since these typically include a homogeneous population and only one variant of the intervention. This limitation can be bypassed by using meta-analysis. Meta-analysis allows the researcher to compare the treatment effect in different subgroups, even if these subgroups appear in separate studies. We discuss several statistical issues related to this procedure, including the selection of a statistical model and statistical power for the comparison. To illustrate these points, we use the example of a meta-analysis of obesity prevention.

Borst, J. P. and J. R. Anderson (2013). "Using model-based functional MRI to locate working memory updates and declarative memory retrievals in the fronto-parietal network." Proc Natl Acad Sci U S A 110(5): 1628-33.

In this study, we used model-based functional MRI (fMRI) to locate two functions of the fronto-parietal network: declarative memory retrievals and updating of working memory. Because regions in the fronto-parietal network are by definition coherently active, locating functions within this network is difficult. To overcome this problem, we applied model-based fMRI, an analysis method that uses predictions of a computational model to inform the analysis. We applied model-based fMRI to five previously published datasets with associated computational cognitive models, and subsequently integrated the results in a meta-analysis. The meta-analysis showed that declarative memory retrievals correlated with activity in the inferior frontal gyrus and the anterior cingulate, whereas updating of working memory corresponded to activation in the inferior parietal lobule, as well as to activation around the inferior frontal gyrus and the anterior cingulate.

Bosetti, C., V. Rosato, et al. (2013). "Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis." Oncologist 18(2): 148-56.

Objective. To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. Methods. A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). Results. Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91-1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07-1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95-1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90-0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48-0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. Conclusions. Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.

Bosquet, L., N. Berryman, et al. (2013). "Effect of training cessation on muscular performance: A meta-analysis." Scand J Med Sci Sports.

The purpose of this study was to assess the effect of resistance training cessation on strength performance through a meta-analysis. Seven databases were searched from which 103 of 284 potential studies met inclusion criteria. Training status, sex, age, and the duration of training cessation were used as moderators. Standardized mean difference (SMD) in muscular performance was calculated and weighted by the inverse of variance to calculate an overall effect and its 95% confidence interval (CI). Results indicated a detrimental effect of resistance training cessation on all components of muscular performance: [submaximal strength; SMD (95% CI) = -0.62 (-0.80 to -0.45), P < 0.01], [maximal force; SMD (95% CI) = -0.46 (-0.54 to -0.37), P < 0.01], [maximal power; SMD (95% CI) = -0.20 (-0.28 to -0.13), P < 0.01]. A dose-response relationship between the amplitude of SMD and the duration of training cessation was identified. The effect of resistance training cessation was found to be larger in older people (> 65 years old). The effect was also larger in inactive people for maximal force and maximal power when compared with recreational athletes. Resistance training cessation decreases all components of muscular strength. The magnitude of the effect differs according to training status, age or the duration of training cessation.

Bosteels, J., J. Kasius, et al. (2013). "Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities." Cochrane Database Syst Rev 1: CD009461.

BACKGROUND: Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions, which are detectable in 10% to 15% of women seeking treatment for subfertility. OBJECTIVES: To assess the effects of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions suspected on ultrasound, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods in women with otherwise unexplained subfertility or prior to intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Specialised Register (6 August 2012), the Cochrane Central Register of Controlled Trials (T he Cochrane Library 2012, Issue 7), MEDLINE (1950 to October 2012), EMBASE (1974 to October 2012), CINAHL (from inception to October 2012) and other electronic sources of trials including trial registers, sources of unpublished literature and reference lists. We handsearched the American Society for Reproductive Medicine (ASRM) conference abstracts and proceedings (from January 2008 to October 2012) and we contacted experts in the field. SELECTION CRITERIA: Randomised comparisons between operative hysteroscopy versus control in women with otherwise unexplained subfertility or undergoing IUI, IVF or ICSI and suspected major uterine cavity abnormalities diagnosed by ultrasonography, saline infusion/gel instillation sonography, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods. Primary outcomes were live birth and hysteroscopy complications. Secondary outcomes were pregnancy and miscarriage. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and risk of bias, and extracted data. We contacted study authors for additional information. MAIN RESULTS: Two studies met the inclusion criteria and neither reported the primary outcomes of live birth and complications from the procedure. In women with otherwise unexplained subfertility and submucous fibroids, there is no evidence of benefit with hysteroscopic myomectomy compared to regular fertility-oriented intercourse during 12 months for clinical pregnancy (odds ratio (OR) 2.4, 95% confidence interval (CI) 0.97 to 6.2, P = 0.06, 94 women) and miscarriage (OR 1.5, 95% CI 0.47 to 5.0, P = 0.47, 94 women) (very low-quality evidence). The hysteroscopic removal of polyps prior to IUI increases the odds of clinical pregnancy (experimental event rate (EER) 63%) compared to diagnostic hysteroscopy and polyp biopsy only (control event rate (CER) 28%) (OR 4.4, 95% CI 2.5 to 8.0, P < 0.00001, 204 women, high-quality evidence). AUTHORS' CONCLUSIONS: Hysteroscopic myomectomy might increase the odds of clinical pregnancy in women with unexplained subfertility and submucous fibroids, but the evidence is at present not conclusive. The hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI might increase the clinical pregnancy rate. More randomised studies are needed to substantiate the effectiveness of the hysteroscopic removal of suspected endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions in women with unexplained subfertility or prior to IUI, IVF or ICSI.

Botling, J., K. Edlund, et al. (2013). "Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation." Clin Cancer Res 19(1): 194-204.

PURPOSE: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap. EXPERIMENTAL DESIGN: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860). RESULTS: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate <1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup. CONCLUSIONS: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics.

Bousema, T., T. S. Churcher, et al. (2013). "Can field-based mosquito feeding assays be used for evaluating transmission-blocking interventions?" Trends Parasitol 29(2): 53-9.

A recent meta-analysis of mosquito feeding assays to determine the Plasmodium falciparum transmission potential of naturally infected gametocyte carriers highlighted considerable variation in transmission efficiency between assay methodologies and between laboratories. This begs the question as to whether mosquito feeding assays should be used for the evaluation of transmission-reducing interventions in the field and whether these field-based mosquito assays are currently standardized sufficiently to enable accurate evaluations. Here, we address biological and methodological reasons for the observed variations, discuss whether these preclude the use of field-based mosquito feeding assays in field evaluations of transmission-blocking interventions, and propose how we can maximize the precision of estimates. Altogether, we underscore the significant advantages of field-based mosquito feeding assays in basic malaria research and field trials.

Bower, P., E. Kontopantelis, et al. (2013). "Influence of initial severity of depression on effectiveness of low intensity interventions: meta-analysis of individual patient data." BMJ 346: f540.

OBJECTIVE: To assess how initial severity of depression affects the benefit derived from low intensity interventions for depression. DESIGN: Meta-analysis of individual patient data from 16 datasets comparing low intensity interventions with usual care. SETTING: Primary care and community settings. PARTICIPANTS: 2470 patients with depression. INTERVENTIONS: Low intensity interventions for depression (such as guided self help by means of written materials and limited professional support, and internet delivered interventions). MAIN OUTCOME MEASURES: Depression outcomes (measured with the Beck Depression Inventory or Center for Epidemiologic Studies Depression Scale), and the effect of initial depression severity on the effects of low intensity interventions. RESULTS: Although patients were referred for low intensity interventions, many had moderate to severe depression at baseline. We found a significant interaction between baseline severity and treatment effect (coefficient -0.1 (95% CI -0.19 to -0.002)), suggesting that patients who are more severely depressed at baseline demonstrate larger treatment effects than those who are less severely depressed. However, the magnitude of the interaction (equivalent to an additional drop of around one point on the Beck Depression Inventory for a one standard deviation increase in initial severity) was small and may not be clinically significant. CONCLUSIONS: The data suggest that patients with more severe depression at baseline show at least as much clinical benefit from low intensity interventions as less severely depressed patients and could usefully be offered these interventions as part of a stepped care model.

Bowering, K. J., N. E. O'Connell, et al. (2013). "The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis." J Pain 14(1): 3-13.

Graded motor imagery (GMI) is becoming increasingly used in the treatment of chronic pain conditions. The objective of this systematic review was to synthesize all evidence concerning the effects of GMI and its constituent components on chronic pain. Systematic searches were conducted in 10 electronic databases. All randomized controlled trials (RCTs) of GMI, left/right judgment training, motor imagery, and mirror therapy used as a treatment for chronic pain were included. Methodological quality was assessed using the Cochrane risk of bias tool. Six RCTs met our inclusion criteria, and the methodological quality was generally low. No effect was seen for left/right judgment training, and conflicting results were found for motor imagery used as stand-alone techniques, but positive effects were observed for both mirror therapy and GMI. A meta-analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2 studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71]; heterogeneity, I(2) = 15%). Our results suggest that GMI and mirror therapy alone may be effective, although this conclusion is based on limited evidence. Further rigorous studies are needed to investigate the effects of GMI and its components on a wider chronic pain population. PERSPECTIVE: This systematic review synthesizes the evidence for GMI and its constituent components on chronic pain. This review may assist clinicians in making evidence-based decisions on managing patients with chronic pain conditions.

Boysen, G. A. and A. VanBergen (2013). "A review of published research on adult dissociative identity disorder: 2000-2010." J Nerv Ment Dis 201(1): 5-11.

The purpose of this study was to assess the scientific and etiological status of dissociative identity disorder (DID) by examining cases published from 2000 to 2010. In terms of scientific status, DID is a small but ongoing field of study. The review yielded 21 case studies and 80 empirical studies, presenting data on 1171 new cases of DID. A mean of 9 articles, each containing a mean of 17 new cases of DID, emerged each year. In terms of etiological status, many of the central criticisms of the disorder's validity remain unaddressed. Most cases of DID emerged from a small number of countries and clinicians. In addition, documented cases occurring outside treatment were almost nonexistent. Finally, people simulating DID in the laboratory were mostly indistinguishable from individuals with DID. Overall, DID is still a topic of study, but the research lacks the productivity and focus needed to resolve ongoing controversies surrounding the disorder.

Bradbury, C. L., S. I. Singh, et al. (2013). "Prevention of post-dural puncture headache in parturients: a systematic review and meta-analysis." Acta Anaesthesiol Scand 57(4): 417-430.

Post-dural puncture headaches (PDPHs) present an important clinical problem. We assessed methods to decrease accidental dural punctures (ADPs) and interventions to reduce PDPH following ADP. Multiple electronic databases were searched for randomised clinical trials (RCTs) of parturients having labour epidurals, in which the studied intervention could plausibly affect ADP or PDPH, and the incidence of at least one of these was recorded. Forty RCTs (n = 11,536 epidural insertions) were included, studying combined spinal-epidurals (CSEs), loss of resistance medium, prophylactic epidural blood patches, needle bevel orientation, ultrasound-guided insertion, epidural morphine, Special Sprotte needles, acoustic-guided insertion, administration of cosyntropin, and continuous spinal analgesia. The RCTs for CSE, loss of resistance medium, and prophylactic epidural blood patches were meta-analysed. Five methods reduced PDPH: prophylactic epidural blood patch {four trials, median quality score = 2, risk difference = -0.48 [95% confidence interval (CI): -0.88 to -0.086]}, lateral positioning of the epidural needle bevel upon insertion (one trial, quality score = 1), Special Sprotte needles [one trial, quality score = 5, risk difference = -0.44 (95% CI: -0.67 to -0.21)], epidural morphine [one trial, quality score = 4, risk difference = -0.36 (95% CI -0.59 to -0.13)], and cosyntropin [one trial, quality score = 5, risk difference = -0.36 (95% CI -0.55 to -0.16)]. Several methods potentially reduce PDPH. Special Sprotte needles, epidural morphine, and cosyntropin are thus far each supported by a single, albeit good quality trial. Prophylactic blood patches are supported by three trials, but these had flawed methodology. Mostly, trials were of limited quality, and further well-conducted, large studies are needed.

Brady, T. J., L. Murphy, et al. (2013). "A meta-analysis of health status, health behaviors, and healthcare utilization outcomes of the Chronic Disease Self-Management Program." Prev Chronic Dis 10: 120112.

INTRODUCTION: The Chronic Disease Self-Management Program (CDSMP) is a community-based self-management education program designed to help participants gain confidence (self-efficacy) and skills to better manage their chronic conditions; it has been implemented worldwide. The objective of this meta-analysis was to quantitatively synthesize the results of CDSMP studies conducted in English-speaking countries to determine the program's effects on health behaviors, physical and psychological health status, and health care utilization at 4 to 6 months and 9 to 12 months after baseline. METHODS: We searched 8 electronic databases to identify CDSMP-relevant literature published from January 1, 1999, through September 30, 2009; experts identified additional unpublished studies. We combined the results of all eligible studies to calculate pooled effect sizes. We included 23 studies. Eighteen studies presented data on small English-speaking groups; we conducted 1 meta-analysis on these studies and a separate analysis on results by other delivery modes. RESULTS: Among health behaviors for small English-speaking groups, aerobic exercise, cognitive symptom management, and communication with physician improved significantly at 4- to 6-month follow-up; aerobic exercise and cognitive symptom management remained significantly improved at 9 to 12 months. Stretching/strengthening exercise improved significantly at 9 to 12 months. All measures of psychological health improved significantly at 4 to 6 months and 9 to 12 months. Energy, fatigue, and self-rated health showed small but significant improvements at 4 to 6 months but not at 9 to 12 months. The only significant change in health care utilization was a small improvement in the number of hospitalization days or nights at 4 to 6 months CONCLUSION: Small to moderate improvements in psychological health and selected health behaviors that remain after 12 months suggest that CDSMP delivered in small English-speaking groups produces health benefits for participants and would be a valuable part of comprehensive chronic disease management strategy.

Braini, A., P. Narisetty, et al. (2013). "Double PPH Technique for Hemorrhoidal Prolapse: A Multicentric, Prospective, and Nonrandomized Trial." Surg Innov.

Introduction. Longo's technique (or PPH technique) is well known worldwide. Meta-analysis suggests that the failure due to persistence or recurrence is close to 7.7%. One of the reasons for the recurrence is the treatment of the advanced hemorrhoidal prolapse with a single stapling device, which is not enough to resect the appropriate amount of prolapse. Materials and methods. We describe the application of "Double PPH Technique" (D-PPH) to treat large hemorrhoidal prolapses. We performed a multicentric, prospective, and nonrandomized trial from July 2008 to July 2009, wherein 2 groups of patients with prolapse and hemorrhoids were treated with a single PPH or a D-PPH. Results were compared. The primary outcome was evaluation of safety and efficacy of the D-PPH procedure in selected patients with large hemorrhoidal prolapse. Results. In all, 281 consecutive patients suffering from hemorrhoidal prolapse underwent surgery, of whom 74 were assigned intraoperatively to D-PPH, whereas 207 underwent single PPH. Postoperative complications were 5% in both groups (P = .32), in particular: postoperative major bleeding 3.0% in PPH versus 4.1% D-PPH (P = .59); pain 37.9 % PPH versus 27.3% D-PPH (mean visual analog scale [VAS] = 2.5 vs 2.9, respectively; P = .72); and fecal urgency 2.1% PPH versus 5.7% D-PPH (P = .8). Persistence of hemorrhoidal prolapse at 12-month follow-up was 3.7% in the PPH group versus 5.9% in the D-PPH group (P = .5). Conclusions. Our data support the hypothesis that an accurate intraoperative patient selection for single (PPH) or double (D-PPH) stapled technique will lower in a significant way the incidence of recurrence after Longo's procedure for hemorrhoidal prolapse.

Brass, E. P., D. Koster, et al. (2013). "A systematic review and meta-analysis of propionyl-L-carnitine effects on exercise performance in patients with claudication." Vasc Med 18(1): 3-12.

Propionyl-l-carnitine (PLC) may improve exercise performance in patients with peripheral artery disease, but results from clinical trials have been inconsistent. The safety and efficacy of PLC for treatment of claudication was evaluated by a systematic review and meta-analysis of clinical trials for which data were available through September 2010. Eighty-five studies were identified, of which 13 were randomized controlled trials. Owing to database availability for the six phase III studies carried out with PLC (1 g orally, twice daily), a patient-level meta-analysis was conducted as the primary analysis. Treadmill performance data from these six studies were harmonized to peak walking distance (PWD) on a 7% grade at a speed of 3 km/hour. PLC (n = 440) was associated with a net 16 meter improvement (95% CI, 8-20 meters) in PWD as compared with placebo (n = 427) in the primary analysis (p = 0.002). The effect of PLC was similar in subpopulations defined using clinical and demographic variables, with possible enhanced benefit in patients engaged in an exercise program or enrolled at study sites in Russia. The systematic review of the effect of PLCs on claudication identified seven additional randomized controlled trials for a total of 13 trials, which included 681 patients on placebo and 672 on PLC. This meta-analysis confirmed a 45 meter net improvement on PLC using a random-effects model. In conclusion, oral PLC is associated with a statistically significant increase in PWD in patients with claudication, which may be clinically relevant.

Bringhen, S., M. V. Mateos, et al. (2013). "Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials." Haematologica.

Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatment-related side effects are frequent and full-drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow-up of 33 months (95% CI 10-56 months), 513/1435 patients (36%) died, median overall survival was 50 months (95% CI 46-60 months). The risk of death was increased in patients >/=75 years (HR 1.44, 95% CI 1.20-1.72, P<0.001), in patients with renal failure (HR 2.02, 95% CI 1.51-2.70, P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, 95% CI 1.75-3.64, P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95% CI 1.12-2.51, P=0.01). This increased risk was restricted to the first 6 months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomib-thalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age >/=75 years or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less-intense individualized approaches are suggested in elderly unfit subjects.

Brinjikji, W., M. H. Murad, et al. (2013). "Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis." Stroke 44(2): 442-7.

BACKGROUND AND PURPOSE: Flow diverters are important tools in the treatment of intracranial aneurysms. However, their impact on aneurysmal occlusion rates, morbidity, mortality, and complication rates is not fully examined. METHODS: We conducted a systematic review of the literature searching multiple databases for reports on the treatment of intracranial aneurysms with flow-diverter devices. Random effects meta-analysis was used to pool outcomes of aneurysmal occlusion rates at 6 months, and procedure-related morbidity, mortality, and complications across studies. RESULTS: A total of 29 studies were included in this analysis, including 1451 patients with 1654 aneurysms. Aneurysmal complete occlusion rate was 76% (95% confidence interval [CI], 70%-81%). Procedure-related morbidity and mortality were 5% (95% CI, 4%-7%) and 4% (95% CI, 3%-6%), respectively. The rate of postoperative subarachnoid hemorrhage was 3% (95% CI, 2%-4%). Intraparenchymal hemorrhage rate was 3% (95% CI, 2%-4%). Perforator infarction rate was 3% (95% CI, 1%-5%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.01; 95% CI, 0.00-0.08; P<0.0001). Ischemic stroke rate was 6% (95% CI, 4%-9%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.15; 95% CI, 0.08-0.27; P<0.0001). CONCLUSIONS: This meta-analysis suggests that treatment of intracranial aneurysms with flow-diverter devices is feasible and effective with high complete occlusion rates. However, the risk of procedure-related morbidity and mortality is not negligible. Patients with posterior circulation aneurysms are at higher risk of ischemic stroke, particularly perforator infarction. These findings should be considered when considering the best therapeutic option for intracranial aneurysms.

Brocklehurst, P., A. Gordon, et al. (2013). "Antibiotics for treating bacterial vaginosis in pregnancy." Cochrane Database Syst Rev 1: CD000262.

BACKGROUND: Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Women may have symptoms of a characteristic vaginal discharge but are often asymptomatic. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcomes and, in particular, preterm birth (PTB). Identification and treatment may reduce the risk of PTB and its consequences. OBJECTIVES: To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2012), searched cited references from retrieved articles and reviewed abstracts, letters to the editor and editorials. SELECTION CRITERIA: Randomised trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis or intermediate vaginal flora whether symptomatic or asymptomatic and detected through screening. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: We included 21 trials of good quality, involving 7847 women diagnosed with bacterial vaginosis or intermediate vaginal flora.Antibiotic therapy was shown to be effective at eradicating bacterial vaginosis during pregnancy (average risk ratio (RR) 0.42; 95% confidence interval (CI) 0.31 to 0.56; 10 trials, 4403 women; random-effects, T(2) = 0.19, I(2) = 91%). Antibiotic treatment also reduced the risk of late miscarriage (RR 0.20; 95% CI 0.05 to 0.76; two trials, 1270 women, fixed-effect, I(2) = 0%).Treatment did not reduce the risk of PTB before 37 weeks (average RR 0.88; 95% CI 0.71 to 1.09; 13 trials, 6491 women; random-effects, T(2) = 0.06, I(2) = 48%), or the risk of preterm prelabour rupture of membranes (RR 0.74; 95% CI 0.30 to 1.84; two trials, 493 women). It did increase the risk of side-effects sufficient to stop or change treatment (RR 1.66; 95% CI 1.02 to 2.68; four trials, 2323 women, fixed-effect, I(2) = 0%).In this updated review, treatment before 20 weeks' gestation did not reduce the risk of PTB less than 37 weeks (average RR 0.85; 95% CI 0.62 to 1.17; five trials, 4088 women; random-effects, T(2) = 0.06, I(2) = 49%).In women with a previous PTB, treatment did not affect the risk of subsequent PTB (average RR 0.78; 95% CI 0.42 to 1.48; three trials, 421 women; random-effects, T(2) = 0.19, I(2) = 72%).In women with abnormal vaginal flora (intermediate flora or bacterial vaginosis), treatment may reduce the risk of PTB before 37 weeks (RR 0.53; 95% CI 0.34 to 0.84; two trials, 894 women).One small trial of 156 women compared metronidazole and clindamycin, both oral and vaginal, with no significant differences seen for any of the pre-specified primary outcomes. Statistically significant differences were seen for the outcomes of prolongation of gestational age (days) (mean difference (MD) 1.00; 95% CI 0.26 to 1.74) and birthweight (grams) (MD 75.18; 95% CI 25.37 to 124.99) however these represent relatively small differences in the clinical setting.Oral antibiotics versus vaginal antibiotics did not reduce the risk of PTB (RR 1.09; 95% CI 0.78 to 1.52; two trials, 264 women). Oral antibiotics had some advantage over vaginal antibiotics (whether metronidazole or clindamycin) with respect to admission to neonatal unit (RR 0.63; 95% CI 0.42 to 0.92, one trial, 156 women), prolongation of gestational age (days) (MD 9.00; 95% CI 8.20 to 9.80; one trial, 156 women) and birthweight (grams) (MD 342.13; 95% CI 293.04 to 391.22; one trial, 156 women).Different frequency of dosing of antibiotics was assessed in one small trial and showed no significant difference for any outcome assessed. AUTHORS' CONCLUSIONS: Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. The overall risk of PTB was not significantly reduced. This review provides little evidence that screening and treating all pregnant women with bacterial vaginosis will prevent PTB and its consequences. When screening criteria were broadened to include women with abnormal flora there was a 47% reduction in preterm birth, however this is limited to two included studies.

Broeders, J. A., D. J. Roks, et al. (2013). "Laparoscopic Anterior 180-Degree Versus Nissen Fundoplication for Gastroesophageal Reflux Disease: Systematic Review and Meta-Analysis of Randomized Clinical Trials." Ann Surg.

OBJECTIVE:: To compare short- and long-term outcome after 180-degree laparoscopic anterior fundoplication (180-degree LAF) with laparoscopic Nissen fundoplication (LNF). SUMMARY OF BACKGROUND DATA:: LNF is currently the most frequently performed surgical therapy for gastroesophageal reflux disease. Alternatively, 180-degree LAF has been alleged to reduce troublesome dysphagia and gas-related symptoms, with similar reflux control. METHODS:: MEDLINE, EMBASE, Cochrane Library, and web of Knowledge CPCI-S were searched for randomized clinical trials comparing primary 180-degree LAF with LNF. The methodological quality was evaluated to assess bias risk. Primary outcomes were esophageal acid exposure, esophagitis, heartburn score, dilatation for dysphagia, modified Dakkak dysphagia score (0-45), and reoperation rate. Meta-analysis was conducted at 1 and 5 years. RESULTS:: Five distinct randomized clinical trials comparing 180-degree LAF (n = 227) with LNF (n = 231) were identified. At 1 year, the Dakkak dysphagia score [2.8 vs 4.8; weighted mean difference: -2.25; 95% confidence interval (CI): -2.66 to -1.83; P < 0.001], gas bloating [11% vs 18%; relative risk (RR) 0.59; 95% CI: 0.36-0.97; P = 0.04], flatulence (14% vs 25%; RR: 0.57; 95% CI: 0.35-0.91; P = 0.02), inability to belch (19% vs 31%; RR: 0.63; 95% CI: 0.40-0.99; P = 0.05), and inability to relieve bloating (34% vs 44%; RR: 0.74; 95% CI: 0.55-0.99; P = 0.04) were lower after 180-degree LAF. Esophageal acid exposure (standardized mean difference: 0.19; 95% CI: -0.07 to 0.46; P = 0.15), esophagitis (19% vs 13%; RR: 1.42; 95% CI: 0.69-2.91; P = 0.34), heartburn score (standardized mean difference: 1.27; 95% CI:-0.36 to 2.90; P = 0.13), dilatation rate (1.4% vs 2.8%; RR: 0.60; 95% CI: 0.19-1.91; P = 0.39), reoperation rate (5.7% vs 2.8%; RR: 2.08; 95% CI: 0.80-5.41; P = 0.13), perioperative outcome, regurgitation, proton pump inhibitor (PPI) use, lower esophageal sphincter pressure, and patient satisfaction were similar after 180-degree LAF and LNF. At 5 years, the Dakkak dysphagia score, flatulence, inability to belch, and inability to relieve bloating remained lower after 180-degree LAF. The 5-year heartburn score, dilatation rate, reoperation rate, PPI use, and patient satisfaction were similar. CONCLUSIONS:: At 1 and 5 years, dysphagia and gas-related symptoms are lower after 180-degree LAF than after LNF, and esophageal acid exposure and esophagitis are similar, with no differences in heartburn scores, patient satisfaction, dilatations, and reoperation rate. These results lend level 1a support for the use of 180-degree LAF for the surgical treatment of gastroesophageal reflux disease.

Broer, L., V. Codd, et al. (2013). "Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect." Eur J Hum Genet.

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r=0.42; P-value=3.60 x 10(-61)) than father-offspring correlation (r=0.33; P-value=7.01 x 10(-5)), and a significant positive association with paternal age at offspring birth (beta=0.005; P-value=7.01 x 10(-5)). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 x 10(-30)) was seen, which appeared stronger in older spouse pairs (mean age >/=55 years; r=0.31; P-value=4.27 x 10(-23)) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 x 10(-10)). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.European Journal of Human Genetics advance online publication, 16 January 2013; doi:10.1038/ejhg.2012.303.

Broer, S. L., J. van Disseldorp, et al. (2013). "Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach." Hum Reprod Update 19(1): 26-36.

BACKGROUND Although ovarian reserve tests (ORTs) are frequently used prior to IVF treatment for outcome prediction, their added predictive value is unclear. We assessed the added value of ORTs to patient characteristics in the prediction of IVF outcome. METHODS An individual patient data (IPD) meta-analysis from published studies was performed. Studies on FSH, anti-Mullerian hormone (AMH) or antral follicle count (AFC) in women undergoing IVF were identified and authors were contacted. Using random intercept logistic regression models, we estimated the added predictive value of ORTs for poor response and ongoing pregnancy after IVF, relative to patient characteristics. RESULTS We were able to collect 28 study databases, comprising 5705 women undergoing IVF. The area under the receiver-operating characteristic curve (AUC) for female age in predicting poor response was 0.61. AFC and AMH each significantly improved the model fit (P-value <0.001). Moreover, almost a similar accuracy was reached using AMH or AFC alone (AUC 0.78 and 0.76, respectively). Combining the two tests, however, did not improve prediction (AUC 0.80, P = 0.19) of poor response. In predicting ongoing pregnancy after IVF, age was the best single predictor (AUC 0.57), and none of the ORTs added any value. CONCLUSIONS This IPD meta-analysis demonstrates that AFC and AMH clearly add to age in predicting poor response. As single tests, AFC and AMH both fully cover the prediction of poor ovarian response. In contrast, none of the ORTs add any information to the limited capacity of female age to predict ongoing pregnancy after IVF. The clinical usefulness of ORTs prior to IVF will be limited to the prediction of ovarian response.

Brollo, J., G. Curigliano, et al. (2013). "Adjuvant trastuzumab in elderly with HER-2 positive breast cancer: a systematic review of randomized controlled trials." Cancer Treat Rev 39(1): 44-50.

Trastuzumab, in combination with chemotherapy, is the gold standard in the adjuvant treatment of patients with HER2 positive breast cancer. Limited data are available on the role of adjuvant trastuzumab in the elderly population. We performed a systematic review of prospective randomized trials with available data on the use of adjuvant trastuzumab in patients older than 60years, focusing on both the efficacy and the cardiac safety. Data extrapolated from two prospective trials were included for efficacy and cardiac safety. A significant 47% relative risk reduction was observed in elderly patients receiving trastuzumab compared to chemotherapy alone (pooled Hazard Ratio: 0.53; 95% CI, 0.36-0.77). The pooled proportion of cardiac events in elderly patients treated with trastuzumab was 5% (95% CI, 4-7%). The use of trastuzumab should be considered as a standard of care in the adjuvant therapy of elderly patients with HER-2 positive breast cancer. Acute and chronic medical conditions, nutritional status and level of daily activities should be considered. Uncertainty about cardiac safety in the elderly is a major concern.

Brondum-Jacobsen, P., B. G. Nordestgaard, et al. (2013). "25-Hydroxyvitamin D and symptomatic ischemic stroke: An Original Study and Meta-Analysis." Ann Neurol 73(1): 38-47.

OBJECTIVE: We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population. METHODS: We measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events. RESULTS: Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend </= 2 x 10(-3) ). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (<25.0nmol/l [<10.0ng/ml]) to individuals with optimal vitamin D status (>/=75.0nmol/l [>/=30.0ng/ml]), the multivariate adjusted hazard ratio of ischemic stroke was 1.36 (1.09-1.70). 25-Hydroxyvitamin D concentrations were not associated with risk of hemorrhagic stroke. In a meta-analysis comparing lowest versus highest quartile of 25-hydroxyvitamin D concentrations, the multivariate adjusted odds ratio of ischemic stroke was 1.54 (1.43-1.65) with a corresponding hazard ratio of 1.46 (1.35-1.58) in prospective general population studies. INTERPRETATION: In this large population-based prospective study, we observed stepwise increasing risk of symptomatic ischemic stroke with decreasing plasma 25-hydroxyvitamin D concentrations. This finding was substantiated in a meta-analysis. ANN NEUROL 2013.

Brookwell, M. L., R. P. Bentall, et al. (2013). "Externalizing biases and hallucinations in source-monitoring, self-monitoring and signal detection studies: a meta-analytic review." Psychol Med: 1-11.

BACKGROUND: Cognitive models have postulated that auditory hallucinations arise from the misattribution of internally generated cognitive events to external sources. Several experimental paradigms have been developed to assess this externalizing bias in clinical and non-clinical hallucination-prone samples, including source-monitoring, verbal self-monitoring and auditory signal detection tasks. This meta-analysis aims to synthesize the wealth of empirical findings from these experimental studies. Method A database search was carried out for reports between January 1985 and March 2012. Additional studies were retrieved by contacting authors and screening references of eligible reports. Studies were considered eligible if they compared either (i) hallucinating and non-hallucinating patients with comparable diagnoses, or (ii) non-clinical hallucination-prone and non-prone participants using source-monitoring, verbal self-monitoring or signal detection tasks, or used correlational analyses to estimate comparable effects. RESULTS: The analysis included 15 clinical (240 hallucinating patients and 249 non-hallucinating patients) and nine non-clinical studies (171 hallucination-prone and 177 non-prone participants; 57 participants in a correlation study). Moderate-to-large summary effects were observed in both the clinical and analogue samples. Robust and significant effects were observed in source-monitoring and signal detection studies, but not in self-monitoring studies, possibly due to the small numbers of eligible studies in this subgroup. The use of emotionally valenced stimuli led to effects of similar magnitude to the use of neutral stimuli. CONCLUSIONS: The findings suggest that externalizing biases are important cognitive underpinnings of hallucinatory experiences. Clinical interventions targeting these biases should be explored as possible treatments for clients with distressing voices.

Brown, H. E., N. Pearson, et al. (2013). "Physical activity interventions and depression in children and adolescents : a systematic review and meta-analysis." Sports Med 43(3): 195-206.

CONTEXT: Evidence suggests chronic physical activity (PA) participation may be both protective against the onset of and beneficial for reducing depressive symptoms. OBJECTIVE: The aim of this article is to assess the impact of PA interventions on depression in children and adolescents using meta-analysis. DATA SOURCES: Published English language studies were located from manual and computerized searches of the following databases: PsycInfo, The Cochrane Database of Systematic Reviews and The Cochrane Central Register of Controlled Trials, Trials Register of Promoting Health Interventions (TRoPHI; EPPI Centre), Web of Science and MEDLINE. STUDY SELECTION: Studies meeting inclusion criteria (1) reported on interventions to promote or increase PA; (2) included children aged 5-11 years and/or adolescents aged 12-19 years; (3) reported on results using a quantitative measure of depression; (4) included a non-physical control or comparison group; and (5) were published in peer-reviewed journals written in English, up to and including May 2011 (when the search was conducted). DATA EXTRACTION: Studies were coded for methodological, participant and study characteristics. Comprehensive Meta-Analysis version-2 software was used to compute effect sizes, with subgroup analyses to identify moderating characteristics. Study quality was assessed using the Delphi technique. RESULTS: Nine studies were included (n = 581); most were school-based randomized controlled trials, randomized by individual. Studies used a variety of measurement tools to assess depressive symptoms. The summary treatment effect was small but significant (Hedges' g = -0.26, standard error = 0.09, 95% confidence intervals = -0.43, -0.08, p = 0.004). Subgroup analyses showed that methodological (e.g. studies with both education and PA intervention; those with a higher quality score; and less than 3 months in duration) and participant characteristics (e.g. single-gender studies; those targeting overweight or obese groups) contributed most to the reduction in depression. CONCLUSIONS: There was a small significant overall effect for PA on depression. More outcome-focused, high-quality trials are required to effectively inform the implementation of programmes to reduce depressive symptoms in children and adolescents.

Brown, K. A., N. Khanafer, et al. (2013). "Antibiotics and the risk of community-associated Clostridium difficile infection (CDI): a meta-analysis." Antimicrob Agents Chemother.

The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposures to high risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. EMBASE and PubMed were queried without restriction to date or language. Comparative observational studies and RCTs considering the impact of antibiotic exposures on CDI risk among non-hospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random effects meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR=16.80, 95% confidence interval [CI]: 7.48-37.76), fluoroquinolones (OR=5.50, 95% CI: 4.26-7.11) and cephalosporins, monobactams and carbapenems (CMCs, OR=5.68, 95% CI: 2.12-15.23) had the largest effects, while macrolides (OR=2.65, 95% CI: 1.92-3.64), sulfonamides and trimethoprim (OR=1.81, 95% CI: 1.34-2.43) and penicillins (OR=2.71, 95% CI: 1.75-4.21) had lesser associations with CDI. We noted no effect of tetracyclines on CDI risk (OR=0.92, 95% CI: 0.61-1.40). In the community setting, there is substantial variation in risk of CDI associated with different antimicrobial classes. Avoidance of high risk antibiotics (such as clindamycin, CMCs and fluoroquinolones) in favor of lower risk antibiotics (such as penicillins, macrolides and tetracyclines) may help reduce the incidence of CDI.

Brown, M. C., K. E. Best, et al. (2013). "Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis." Eur J Epidemiol 28(1): 1-19.

There is increasing evidence that pre-eclampsia, a principal cause of maternal morbidity, may also be a risk factor for future cardiovascular and cerebrovascular events. This review aimed to assess the current evidence and quantify the risks of cardiovascular disease (CVD), cerebrovascular events and hypertension associated with prior diagnosis of pre-eclampsia. Medline and Embase were searched with no language restrictions, as were core journals and reference lists from reviews up until January 2012. Case-control and cohort studies which reported cardiovascular and cerebrovascular diseases or hypertension diagnosed more than 6 weeks postpartum, in women who had a history of pre-eclampsia relative to women who had unaffected pregnancies, were included. Fifty articles were included in the systematic review and 43 in the meta-analysis. Women with a history of pre-eclampsia or eclampsia were at significantly increased odds of fatal or diagnosed CVD [odds ratio (OR) = 2.28, 95 % confidence interval (CI): 1.87, 2.78], cerebrovascular disease (OR = 1.76, 95 % CI 1.43, 2.21) and hypertension [relative risk (RR) = 3.13, 95 % CI 2.51, 3.89]. Among pre-eclamptic women, pre-term delivery was not associated with an increased risk of a future cardiovascular event (RR = 1.32, 95 % CI 0.79, 2.22). Women diagnosed with pre-eclampsia are at increased risk of future cardiovascular or cerebrovascular events, with an estimated doubling of odds compared to unaffected women. This has implications for the follow-up of all women who experience pre-eclampsia, not just those who deliver pre-term. This association may reflect shared common risk factors for both pre-eclampsia and cardiovascular and cerebrovascular disease.

Brown, T., G. Pilkington, et al. (2013). "Clinical effectiveness of first-line chemoradiation for adult patients with locally advanced non-small cell lung cancer: a systematic review." Health Technol Assess 17(6): 1-99.

BACKGROUND: The National Institute for Health and Clinical Excellence has issued guidelines on the treatment of non-small cell lung cancer (NSCLC) and recommends that patients with stage IIIA-IIIB disease who are not amenable to surgery be treated with potentially curative chemoradiation (CTX-RT). This review was conducted as part of a larger systematic review of all first-line chemotherapy (CTX) and CTX-RT treatments for patients with locally advanced or metastatic NSCLC. However, it was considered that patients with potentially curable disease (e.g. stage IIIA) are different from those with advanced disease, who are suitable for palliative treatment only, and therefore the results should be reported separately. OBJECTIVE: To evaluate the clinical effectiveness of first-line CTX in addition to radiotherapy (RT) (CTX-RT vs CTX-RT) for adult patients with locally advanced NSCLC who are suitable for potentially curative treatment. DATA SOURCES: Three electronic databases (MEDLINE, EMBASE and The Cochrane Library) were searched from January 1990 to September 2010. REVIEW METHODS: Inclusion criteria comprised adult patients with locally advanced NSCLC, trials that compared any first-line CTX-RT therapy (induction, sequential, concurrent and consolidation) and outcomes of overall survival (OS) and/or progression-free survival (PFS). The results of clinical data extraction and quality assessment were summarised in tables and with narrative description. Direct meta-analyses using OS data were undertaken where possible: sequential CTX-RT compared with concurrent CTX-RT; sequential CTX-RT compared with concurrent/consolidation CTX-RT; and sequential CTX-RT compared with concurrent CTX-RT with or without consolidation. There were not sufficient data to perform meta-analysis on PFS. RESULTS: Of the 240 potentially relevant studies that were published post 2000, 19 met the inclusion criteria and compared CTX-RT with CTX-RT. The results from the OS meta-analysis comparing sequential CTX-RT with concurrent CTX-RT appear to show an OS advantage for concurrent CTX-RT arms over sequential arms; this result is not statistically significant [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.50 to 1.25)]. The results from the OS meta-analysis comparing sequential CTX-RT with concurrent/consolidation CTX-RT appear to show a statistically significant OS advantage for concurrent/consolidation CTX-RT treatment over sequential treatment (HR 0.68; 95% CI 0.55 to 0.83). The results from the OS meta-analysis comparing sequential CTX-RT with concurrent CTX-RT with or without consolidation appear to show a statistically significant OS advantage for concurrent CTX-RT with or without consolidation over sequential treatment (HR 0.72; 95% CI 0.61 to 0.84). LIMITATIONS: This report provides a summary and critical appraisal of a comprehensive evidence base of CTX-RT trials; however, it is possible that additional trials have been reported since our last literature search. It is disappointing that the quality of the research in this area does not meet the accepted quality standards regarding trial design and reporting. CONCLUSIONS: This review identified that the research conducted in the area of CTX-RT was generally of poor quality and suffered from a lack of reporting of all important clinical findings, including OS. The 19 trials included in the systematic review were too disparate to form any conclusions as to the effectiveness of individual CTX agents or types of RT. The focus of primary research should be good methodological quality; appropriate allocation of concealment and randomisation, and comprehensive reporting of key outcomes, will enable meaningful synthesis and conclusions to be drawn. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Bruce, J. and A. Sutherland (2013). "Surgical versus conservative interventions for displaced intra-articular calcaneal fractures." Cochrane Database Syst Rev 1: CD008628.

BACKGROUND: Fractures of the calcaneus (heel bone) comprise up to 2% of all fractures. These fractures are mostly caused by a fall from a height, and are common in younger adults. Treatment can be surgical or non-surgical; however, there is clinical uncertainty over optimal management. OBJECTIVES: To assess the effects of surgical compared with conservative treatment of displaced intra-articular calcaneal fractures in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to July 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 3), MEDLINE (1948 to July 2011), EMBASE (1980 to 2011 Week 27), the WHO International Clinical Trials Registry Platform, Current Controlled Trials, and Orthopaedic Trauma Association annual meeting archives (1996 to 2011). Reference lists of retrieved articles were checked. No language restrictions were applied. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical studies comparing surgical versus conservative management for displaced intra-articular calcaneal fractures. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, selected studies, extracted data and assessed risk of bias. Primary outcomes were function (e.g. walking ability) and chronic pain. Risk ratios were calculated for dichotomous outcomes and mean differences for continuous outcomes. Missing standard deviations were calculated from P values. MAIN RESULTS: Four trials were included (602 participants). Three trials were small single-centre trials, and the fourth a large multi-centre trial including 424 participants. All trials had methodological flaws, usually failure to conceal allocation and incomplete follow-up data, which put them at high risk of bias. Follow-up ranged from 1 to 15 years after treatment.Data for functional outcomes, including walking ability, from three trials could not be pooled. The strongest evidence was from the multi-centre trial. This showed no statistically or clinically significant differences between the surgical and conservatively treated groups at three years follow-up in the ''validated disease-specific" score (0 to 100: perfect result; 424 participants; mean difference (MD) 4.30, 95% confidence interval (CI) -1.11 to 9.71; P = 0.12). There was no significant difference between the two groups in the risk of chronic pain at follow-up (19/40 versus 24/42; risk ratio (RR) 0.79, 95% CI 0.53 to 1.18; 2 trials). The multi-centre trial found no statistically or clinically significant difference between the two groups in health-related quality of life at three years follow-up (SF-36 (0 to 100: best outcome): MD 4.00, 95% CI -1.16 to 9.16; P = 0.13).Two small trials provided some limited evidence of a tendency for a higher return to previous employment after surgery (27/34 versus 15/27; RR 1.45, 95% CI 0.75 to 2.81; I(2) = 55%; 2 trials). One small trial found no difference between the two groups in the ability to wear normal shoes, whereas another small trial found that surgery resulted in more people who were able to wear all shoes comfortably. There was a higher rate of major complications, such as surgical site infection, after surgery compared with conservative treatment (57/206 versus 42/218; RR 1.44, 95% CI 1.01 to 2.04; 1 trial). Conversely, significantly fewer surgical participants had subtalar arthrodeses due to the development of subtalar arthritis (7/206 versus 37/218; RR 0.20, 95% CI 0.09 to 0.44; 1 trial). There were no significant differences between the two groups in range of movement outcomes or radiological measurements (e.g. Bohler's angle). AUTHORS' CONCLUSIONS: The bulk of the evidence in this review derives from one large multi-centre but inadequately reported trial conducted over 15 years ago. This found no significant differences between surgical or conservative treatment in functional ability and health related quality of life at three years after displaced intra-articular calcaneal fracture. Though it reported a greater risk of major complications after surgery, subtalar arthrodeses for the development of subtalar arthritis was significantly greater after conservative treatment.Overall, there is insufficient high quality evidence relating to current practice to establish whether surgical or conservative treatment is better for adults with displaced intra-articular calcaneal fracture. Evidence from adequately powered randomised, multi-centre controlled trials, assessing patient-centred and clinically relevant outcomes is required. However, it would be prudent to reassess this need after an update of the review that incorporates new evidence from a currently ongoing multi-centre trial.

Brusselaers, N., S. Labeau, et al. (2013). "Value of lower respiratory tract surveillance cultures to predict bacterial pathogens in ventilator-associated pneumonia: systematic review and diagnostic test accuracy meta-analysis." Intensive Care Med 39(3): 365-75.

PURPOSE: In ventilator-associated pneumonia (VAP), early appropriate antimicrobial therapy may be hampered by involvement of multidrug-resistant (MDR) pathogens. METHODS: A systematic review and diagnostic test accuracy meta-analysis were performed to analyse whether lower respiratory tract surveillance cultures accurately predict the causative pathogens of subsequent VAP in adult patients. Selection and assessment of eligibility were performed by three investigators by mutual consideration. Of the 525 studies retrieved, 14 were eligible for inclusion (all in English; published since 1994), accounting for 791 VAP episodes. The following data were collected: study and population characteristics; in- and exclusion criteria; diagnostic criteria for VAP; microbiological workup of surveillance and diagnostic VAP cultures. Sub-analyses were conducted for VAP caused by Staphylococcus aureus, Pseudomonas spp., and Acinetobacter spp., MDR microorganisms, frequency of sampling, and consideration of all versus the most recent surveillance cultures. RESULTS: The meta-analysis showed a high accuracy of surveillance cultures, with pooled sensitivities up to 0.75 and specificities up to 0.92 in culture-positive VAP. The area under the curve (AUC) of the hierarchical summary receiver-operating characteristic curve demonstrates moderate accuracy (AUC: 0.90) in predicting multidrug resistance. A sampling frequency of >2/week (sensitivity 0.79; specificity 0.96) and consideration of only the most recent surveillance culture (sensitivity 0.78; specificity 0.96) are associated with a higher accuracy of prediction. CONCLUSIONS: This study provides evidence for the benefit of surveillance cultures in predicting MDR bacterial pathogens in VAP. However, clinical and statistical heterogeneity, limited samples sizes, and bias remain important limitations of this meta-analysis.

Bryant, A. R., S. B. Wilton, et al. (2013). "Association between QRS duration and outcome with cardiac resynchronization therapy: A systematic review and meta-analysis." J Electrocardiol.

PURPOSE: We conducted a systematic review and meta-analysis of randomized and observational studies to evaluate the associations between QRS duration (QRSd) at baseline or in follow-up and outcomes with cardiac resynchronization therapy (CRT). METHODS: We searched online databases to December 2010 and included 6 randomized controlled trials (RCTs) and 38 observational studies. Outcomes included clinical/functional response, left ventricular (LV) remodeling, hospitalizations and mortality. RESULTS: In RCTs, a benefit of CRT was evident only in patients with QRSd >150ms. In observational studies, those meeting either clinical or remodeling CRT response definitions had both wider pooled baseline QRSd and significantly more QRS narrowing with CRT than non-responders. CONCLUSIONS: RCTs demonstrate that benefit with CRT appears restricted to those with baseline QRSd wider than 150ms. Both wider baseline QRS and more QRS narrowing are associated with CRT response in observational studies. Electrocardiographic QRSd plays an important role in CRT patient selection and follow-up.

Budengeri, P., J. W. Cheng, et al. (2013). "Efficacy and Tolerability of Fixed Combination of Brimonidine 0.2%/Timolol 0.5% Compared with Fixed Combination of Dorzolamide 2%/Timolol 0.5% in the Treatment of Patients with Elevated Intraocular Pressure: A Meta-Analysis of Randomized Controlled Trials." J Ocul Pharmacol Ther.

Abstract Objective: To evaluate the efficacy and tolerability of the fixed-combination brimonidine 0.2%/timolol 0.5% (FCBT) compared with the fixed-combination dorzolamide 2%/timolol 0.5% (FCDT) in the treatment of patients with elevated intraocular pressure (IOP). Methods: Pertinent randomized controlled trials comparing FCBT with FCDT in patients with elevated IOP were identified through systematic searches of the Cochrane Library, PubMed, and EMBASE. The main efficacy measures were the IOP reduction (IOPR), including diurnal mean IOPR, and peak IOPR. The main tolerability measure was the individual adverse events. The pooled estimates and 95% confidence intervals (CIs) were carried out in RevMan version 5.0 software. Results: Seven studies involving 582 patients were included in the meta-analysis. With a weighted mean difference (WMD) of IOPR in diurnal mean of 0.44 mmHg (95% CI, 0.00-0.88), the FCBT was as effective as FCDT in lowering IOP in patients with elevated IOP (P=0.05). The WMD of IOPR at peak was 0.65 mmHg (95% CI, -0.06 to 1.35) (P=0.76), and there was no significant difference between FCBT and FCDT. FCBT caused burning/stinging in less patients than FCDT [pooled relative risk: 0.45 (95% CI, 0.29-0.70)]. Conclusions: Both FCBT and FCDT can effectively lower IOP in patients with elevated IOP, and the IOP-lowering efficacy of FCBT is noninferior to that of FCDT. Additionally, FCBT affords an ocular comfort advantage compared with FCDT.

Buist, K. L., M. Dekovic, et al. (2013). "Sibling relationship quality and psychopathology of children and adolescents: a meta-analysis." Clin Psychol Rev 33(1): 97-106.

In the current meta-analysis, we investigated the link between child and adolescent sibling relationship quality (warmth, conflict and differential treatment) and internalizing and externalizing problems, and potential moderators of these associations. From 34 studies, we obtained 85 effect sizes, based on 12,257 children and adolescents. Results showed that more sibling warmth, less sibling conflict and less differential treatment were all significantly associated with less internalizing and externalizing problems. Effect sizes for sibling conflict were stronger than for sibling warmth and differential treatment, and associations for internalizing and externalizing problems were similar in strength. Effect sizes were moderated by sibling gender combination (stronger effects for higher percentage brother pairs), age difference between siblings (stronger effects for smaller age differences), and developmental period (stronger effect sizes for children than for adolescents). These results indicate that the sibling context is important when considering psychopathology. In addition to the overwhelming evidence of the impact of parent-child and marital relationships on child and adolescent development, the present meta-analysis is a reminder that the sibling relationship warrants more attention in research as well as in clinical settings.

Buldt, A. K., G. S. Murley, et al. (2013). "The relationship between foot posture and lower limb kinematics during walking: A systematic review." Gait Posture.

Variations in foot posture, such as pes planus (low-arched foot) or pes cavus (high-arched foot), are thought to be an intrinsic risk factor for injury due to altered motion of the lower extremity. Hence, the aim of this systematic review was to investigate the relationship between foot posture and lower limb kinematics during walking. A systematic database search of MEDLINE, CINAHL, SPORTDiscus, Embase and Inspec was undertaken in March 2012. Two independent reviewers applied predetermined inclusion criteria to selected articles for review and selected articles were assessed for quality. Articles were then grouped into two broad categories: (i) those comparing mean kinematic parameters between different foot postures, and (ii) those examining associations between foot posture and kinematics using correlation analysis. A final selection of 12 articles was reviewed. Meta-analysis was not conducted due to heterogeneity between studies. Selected articles primarily focused on comparing planus and normal foot postures. Five articles compared kinematic parameters between different foot postures - there was some evidence for increased motion in planus feet, but this was limited by small effect sizes. Seven articles investigated associations between foot posture and kinematics - there was evidence that increasing planus foot posture was positively associated with increased frontal plane motion of the rearfoot. The body of literature provides some evidence of a relationship between pes planus and increased lower limb motion during gait, however this was not conclusive due to heterogeneity between studies and small effect sizes.

Burdett, S., L. Rydewska, et al. (2013). "A closer look at the effects of postoperative radiotherapy by stage and nodal status: Updated results of an individual participant data meta-analysis in non-small-cell lung cancer." Lung Cancer.

Burton, C., B. McKinstry, et al. (2013). "Activity monitoring in patients with depression: a systematic review." J Affect Disord 145(1): 21-8.

BACKGROUND: Altered physical activity is an important feature of depression. It is manifested in psychomotor retardation, agitation and withdrawal from engagement in normal activities. Modern devices for activity monitoring (actigraphs) make it possible to monitor physical activity unobtrusively but the validity of actigraphy as an indicator of mood state is uncertain. We carried out a systematic review of digital actigraphy in patients with depression to investigate the associations between measured physical activity and depression. METHODS: Systematic review and meta-analysis. Studies were identified from Medline, EMBASE and Psycinfo databases and included if they were either case control or longitudinal studies of actigraphy in adults aged between 18 and 65 diagnosed with a depressive disorder. Outcomes were daytime and night-time activity and actigraphic measures of sleep. RESULTS: We identified 19 eligible papers from 16 studies (412 patients). Case control studies showed less daytime activity in patients with depression (standardised mean difference -0.76, 95% confidence intervals -1.05 to -0.47). Longitudinal studies showed moderate increase in daytime activity (0.53, 0.20 to 0.87) and a reduction in night-time activity (-0.36, -0.65 to -0.06) over the course of treatment. LIMITATIONS: All study participants were unblinded. Only seven papers included patients treated in the community. CONCLUSIONS: Actigraphy is a potentially valuable source of additional information about patients with depression. However, there are no clear guidelines for use of actigraphy in studies of patients with depression. Further studies should investigate patients treated in the community. Additional work to develop algorithms for differentiating behaviour patterns is also needed.

Burton, T. P., A. Mittal, et al. (2013). "Nonsteroidal anti-inflammatory drugs and anastomotic dehiscence in bowel surgery: systematic review and meta-analysis of randomized, controlled trials." Dis Colon Rectum 56(1): 126-34.

BACKGROUND: Nonsteroidal anti-inflammatory drugs are a key component of contemporary perioperative analgesia. Recent experimental and observational clinical data suggest an associated increased incidence of anastomotic dehiscence in bowel surgery. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis of anastomotic dehiscence in randomized, controlled trials of perioperative nonsteroidal anti-inflammatory drugs. DATA SOURCES: Published and unpublished trials in any language reported 1990 or later were identified by searching electronic databases, bibliographies, and relevant conference proceedings. STUDY SELECTION: Trials of adults undergoing bowel surgery randomly assigned to perioperative nonsteroidal anti-inflammatory drugs or control were included. The number of patients with a bowel anastomosis and the incidence of anastomotic dehiscence had to be reported or be available from authors for the study to be included. INTERVENTION: At least 1 dose of a nonsteroidal anti-inflammatory drug was given perioperatively within 48 hours of surgery. MAIN OUTCOME MEASURES: The primary outcome measured was 30-day incidence of anastomotic dehiscence as defined by authors. RESULTS: Six trials comprising 480 patients having a bowel anastomosis met inclusion criteria. In 4 studies, anastomotic dehiscence rates were higher in the intervention groups. Overall rates were 14/272 participants (5.1%) in intervention arms vs 5/208 (2.4%) in control arms. Peto OR was 2.16 (95% CI 0.85, 5.53; p = 0.11), and there was no heterogeneity between studies (I statistic 0%). LIMITATIONS: Sizes of available trials were small, preventing firm conclusions and subset analysis of drugs of different cyclooxygenase specificity. A precise and consistent definition of anastomotic dehiscence was not used across trials. CONCLUSIONS: A statistically significant difference in incidence of anastomotic dehiscence was not demonstrated. However, the Peto OR of 2.16 (0.85, 5.53) and lack of heterogeneity between trials suggest that this finding may be due to a lack of power of the available data rather than a lack of effect.

Bush, W. S., J. Boston, et al. (2013). "Enabling high-throughput genotype-phenotype associations in the epidemiologic architecture for genes linked to environment (eagle) project as part of the population architecture using genomics and epidemiology (page) study." Pac Symp Biocomput: 373-84.

Genetic association studies have rapidly become a major tool for identifying the genetic basis of common human diseases. The advent of cost-effective genotyping coupled with large collections of samples linked to clinical outcomes and quantitative traits now make it possible to systematically characterize genotype-phenotype relationships in diverse populations and extensive datasets. To capitalize on these advancements, the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) project, as part of the collaborative Population Architecture using Genomics and Epidemiology (PAGE) study, accesses two collections: the National Health and Nutrition Examination Surveys (NHANES) and BioVU, Vanderbilt University's biorepository linked to de-identified electronic medical records. We describe herein the workflows for accessing and using the epidemiologic (NHANES) and clinical (BioVU) collections, where each workflow has been customized to reflect the content and data access limitations of each respective source. We also describe the process by which these data are generated, standardized, and shared for meta-analysis among the PAGE study sites. As a specific example of the use of BioVU, we describe the data mining efforts to define cases and controls for genetic association studies of common cancers in PAGE. Collectively, the efforts described here are a generalized outline for many of the successful approaches that can be used in the era of high-throughput genotype-phenotype associations for moving biomedical discovery forward to new frontiers of data generation and analysis.

Bushe, C. J. and N. C. Savill (2013). "Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009-2011: Focus on clinical efficacy and safety." J Psychopharmacol.

Background:Clinicians obtain critical prescribing knowledge from clinical papers and review articles. This is the first published systematic review of clinical atomoxetine data covering 2009-2011.Objective:We aim to update clinicians on current clinical atomoxetine data with specific reference to time of onset of efficacy and maximal efficacy. These data may allow critical analysis of comparative efficacy between atomoxetine and stimulant medications.Methods:A formal systematic review of atomoxetine data from January 2009-June 2011 was conducted. The search term used was "atomoxetine" in the English language. The search yielded 747 citations from which 106 are clinical data. This paper includes clinical efficacy and safety data and excludes quality-of-life and review papers.Results:Atomoxetine has an onset of action within 4 weeks (possibly within 1 week in subsequent responders) but requires at least 12 weeks for full response to be demonstrated. Treatment-naive cohorts (6-12 weeks) report effect sizes of 0.6-1.3. Using minimum 6-week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta-analysis, although the diversity of the data makes interpretation complex. From epidemiological databases, cardiovascular and suicide-related events were similar to those seen in patients taking methylphenidate.Conclusions:Incremental response time to atomoxetine should be considered in the design of future comparative efficacy trials.

Butts, M. M., W. J. Casper, et al. (2013). "How important are work-family support policies? A meta-analytic investigation of their effects on employee outcomes." J Appl Psychol 98(1): 1-25.

This meta-analysis examines relationships between work-family support policies, which are policies that provide support for dependent care responsibilities, and employee outcomes by developing a conceptual model detailing the psychological mechanisms through which policy availability and use relate to work attitudes. Bivariate results indicated that availability and use of work-family support policies had modest positive relationships with job satisfaction, affective commitment, and intentions to stay. Further, tests of differences in effect sizes showed that policy availability was more strongly related to job satisfaction, affective commitment, and intentions to stay than was policy use. Subsequent meta-analytic structural equation modeling results indicated that policy availability and use had modest effects on work attitudes, which were partially mediated by family-supportive organization perceptions and work-to-family conflict, respectively. Additionally, number of policies and sample characteristics (percent women, percent married-cohabiting, percent with dependents) moderated the effects of policy availability and use on outcomes. Implications of these findings and directions for future research on work-family support policies are discussed.

Buurma, A. J., R. J. Turner, et al. (2013). "Genetic variants in pre-eclampsia: a meta-analysis." Hum Reprod Update.

BACKGROUNDPre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia.METHODSStudies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model.RESULTSThe literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1.CONCLUSIONSThis meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.

Cadeddu, J. A. (2013). "Re: Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies." J Urol 189(1): 70.

Caeiro, L., J. M. Ferro, et al. (2013). "Apathy secondary to stroke: a systematic review and meta-analysis." Cerebrovasc Dis 35(1): 23-39.

Background: Apathy is a disturbance of motivation, frequent in survivors of stroke. Several studies have evaluated the rate of apathy secondary to stroke and risk factors. Different conclusions and contradictory findings have been published. We aimed to perform a systematic review and meta-analysis of all studies evaluating apathy secondary to stroke to better estimate its rate and risk factors, and explore associations with poorer outcomes. Methods: We searched PubMed, Cochrane Library, PsychINFO and PsycBITE databases and screened references of included studies and review articles for additional citations. Search results and data extraction was performed independently. We systematically reviewed available publications reporting investigations on ischemic and intracerebral hemorrhagic stroke and apathy. Quality assessment of the studies was performed independently. Subgroup analyses were performed according to stroke phase (acute and post-acute), stroke past history (first-ever and any-stroke) and patient age (younger and older patients). Pooled odds ratios (OR) and standardized mean difference, and 95% confidence intervals (CI), were derived by random-effects meta-analysis. Heterogeneity was assessed with I(2) test. Results: From the initial 1,399 publications, we included 19 studies (2,221 patients). The pooled rate of apathy was 36.3% (95% CI 30.3-42.8; I(2) = 46.8), which was similar for acute [39.5% (95% CI 28.9-51.1)] and post-acute phase [34.3% (95% CI 27.8-41.4)], and about three times higher than the rate of depression [12.1% (95% CI 8.2-17.3)]. Apathetic patients were on average 2.74 years older (95% CI 1.25-4.23; I(2) = 0%). No gender differences were found. Depression (OR 2.29; 95% CI 1.41-3.72; I(2) = 44%) and cognitive impairment (OR 2.90; 95% CI 1.09-7.72; I(2) = 14%) were more frequent and severe in apathetic patients. Apathy rate was similar for ischemic and hemorrhagic stroke type and for left- and right-sided hemispheric lesions. Clinical global outcome was similar between apathetic and nonapathetic patients. Conclusion: Apathy secondary to stroke is a more frequent neuropsychiatric disturbance than depression. Apathetic patients are more frequently and severely depressed and cognitively impaired. A negative impact of apathy secondary to stroke on clinical global outcome cannot be ascribed. Future research should properly address its predictor factors and evaluate the impact of apathy treatment options in stroke patients.

Cagliani, R., U. Pozzoli, et al. (2013). "Crohn's Disease Loci Are Common Targets of Protozoa-Driven Selection." Mol Biol Evol.

Previous studies indicated that a few risk variants for autoimmune diseases are subject to pathogen-driven selection. Nonetheless, the proportion of risk loci that has been targeted by pathogens and the type of infectious agent(s) that exerted the strongest pressure remain to be evaluated. We assessed whether different pathogens exerted a pressure on known Crohn's disease (CD) risk variants and demonstrate that these single-nucleotide polymorphisms (SNPs) are preferential targets of protozoa-driven selection (P = 0.008). In particular, 19% of SNPs associated with CD have been subject to protozoa-driven selective pressure. Analysis of P values from genome-wide association studies (GWASs) and meta-analyses indicated that protozoan-selected SNPs display significantly stronger association with CD compared with nonselected variants. This same behavior was not observed for GWASs of other autoimmune diseases. Thus, we integrated selection signatures and meta-analysis results to prioritize five genic SNPs for replication in an Italian cohort. Three SNPs were significantly associated with CD risk, and combination with meta-analysis results yielded P values < 4 x 10(-6). The bona fide risk alleles are located in ARHGEF2, an interactor of NOD2, NSF, a gene involved in autophagy, and HEBP1, encoding a possible mediator of inflammation. Pathway analysis indicated that ARHGEF2 and NSF participate in a molecular network, which also contains VAMP3 (previously associated to CD) and is centered around miR-31 (known to be disregulated in CD). Thus, we show that protozoa-driven selective pressure had a major role in shaping predisposition to CD. We next used this information for the identification of three bona fide novel susceptibility loci.

Cahalin, L. P., P. Chase, et al. (2013). "A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure." Heart Fail Rev 18(1): 79-94.

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO(2)), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO(2)) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO(2) (7,319), VE/VCO(2) slope (5,044), EOV (1,617), and OUES (584). Peak VO(2), the VE/VCO(2) slope and EOV were all highly significant prognostic markers (diagnostic odds ratios >/= 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO(2) and the VE/VCO(2) slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.

Cai, L., S. L. Deng, et al. (2013). "Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population." Hum Genet 132(3): 265-73.

Genetic factors play important roles in the development of tuberculosis (TB). SP110 is a promising candidate target for controlling TB infections. However, several studies associating SP110 single nucleotide polymorphisms (SNPs) with TB have yielded conflicting results. This may be partly resolved by studying other genes associated with SP110, such as MYBBP1A and RELA. Here, we genotyped 6 SP110 SNPs, 8 MYBBP1A SNPs and 5 RELA SNPs in 702 Chinese pulmonary TB patients and 425 healthy subjects using MassARRAY and SNaPshot methods. Using SNP-based analysis with Bonferroni correction, rs3809849 in MYBBP1A [Pcorrected (cor) = 0.0038] and rs9061 in SP110 (Pcor = 0.019) were found to be significantly associated with TB. Furthermore, meta-analysis of rs9061 in East Asian populations showed that the rs9061 T allele conferred significant risk for TB [P = 0.002, pooled odds ratio (OR), 1.24, 95 % confidence interval (CI) = 1.08-1.43]. The MYBBP1A GTCTTGGG haplotype and haplotypes CGACCG/TGATTG within SP110 were found to be markedly and significantly associated with TB (P = 2.00E-06, 5.00E-6 and 2.59E-4, respectively). Gene-based analysis also demonstrated that SP110 and MYBBP1A were each associated with TB (Pcor = 0.011 and 0.035, respectively). The logistic regression analysis results supported interactions between SP110 and MYBBP1A, indicating that subjects carrying a GC/CC genotype in MYBBP1A and CC genotype in SP110 possessed the high risk of developing TB (P = 1.74E-12). Our study suggests that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel marker for identifying the risk of developing TB in the Chinese Han population.

Calanna, S., M. Christensen, et al. (2013). "Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies." Diabetologia.

AIMS/HYPOTHESIS: We carried out a systematic review of clinical studies investigating glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test. METHODS: Random effects models for the primary meta-analysis and random effects meta-regression, subgroup and regression analyses were applied. RESULTS: Random effects meta-analysis of GLP-1 responses in 22 trials during 29 different stimulation tests showed that patients with type 2 diabetes (n = 275) and controls without type 2 diabetes (n = 279) exhibited similar responses of total GLP-1 (p = NS) as evaluated from peak plasma concentrations (weighted mean difference [95% CI] 1.09 pmol/l [-2.50, 4.67]), total AUC (tAUC) (159 pmol/lxmin [-270, 589]), time-corrected tAUC (tAUC min(-1)) (0.99 pmol/l [-1.28, 3.27]), incremental AUC (iAUC) (-122 pmol/lxmin [-410, 165]) and time-corrected iAUC (iAUC min(-1)) (-0.49 pmol/l [-2.16, 1.17]). Fixed effects meta-analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes. Subgroup analysis showed increased responses after a liquid mixed meal test (peak, tAUC and tAUC min(-1)) and after a 50 g OGTT (AUC and tAUC min(-1)), and reduced responses after a solid mixed meal test (tAUC min(-1)) among patients with type 2 diabetes. Meta-regression analyses showed that HbA(1c) and fasting plasma glucose predicted the outcomes iAUC and iAUC min(-1), respectively. CONCLUSIONS/INTERPRETATION: The present analysis suggests that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test, and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion.

Caldarella, C., G. Treglia, et al. (2013). "Diagnostic performance of positron emission tomography using 11C-methionine in patients with suspected parathyroid adenoma: a meta-analysis." Endocrine 43(1): 78-83.

The diagnostic performance of positron emission tomography using (11)C-methionine (MET-PET) in detecting parathyroid adenoma has been investigated by several studies with conflicting results. Aim of our study is to meta-analyze published data about this topic. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through May 2012 and regarding the diagnostic performance of MET-PET in patients with parathyroid adenoma was carried out. No language restriction was used. Only articles in which at least five patients with parathyroid adenoma underwent MET-PET were included in the meta-analysis. Pooled sensitivity and detection rate (DR) on a per patient-based analysis were calculated to assess the diagnostic performance of MET-PET. Nine studies comprising 258 patients with suspected parathyroid adenoma were included in this meta-analysis. Pooled sensitivity and DR values of MET-PET in patients with suspected parathyroid adenoma were 81 % (95 % confidence interval [95 %CI] 74-86 %) and 70 % (95 %CI 62-77 %), respectively, on a per patient-based analysis. The included studies were heterogeneous in their estimate of sensitivity and DR. Our meta-analysis demonstrates that MET-PET is a sensitive and reliable tool in patients with suspected parathyroid adenoma. Thus, this imaging method could be helpful in patients with diagnosis of primary hyperparathyroidism when conventional imaging techniques are negative or inconclusive in localizing parathyroid adenoma.

Calvert, C. and P. C. Ronsmans (2013). "The contribution of hiv to pregnancy-related mortality: a systematic review and meta-analysis." AIDS.

OBJECTIVES:: Whilst much is known about the contribution of HIV to adult mortality, remarkably little is known about the mortality attributable to HIV during pregnancy. In this paper we estimate the proportion of pregnancy-related deaths attributable to HIV based on empirical data from a systematic review of the strength of association between HIV and pregnancy-related mortality. METHODS:: Studies comparing mortality during pregnancy and the postpartum in HIV-infected and uninfected women were included. Summary estimates of the relative and attributable risks for the association between HIV and pregnancy-related mortality were calculated through meta-analyses. Varying estimates of HIV prevalence were used to predict the impact of the HIV epidemic on pregnancy-related mortality at the population level. RESULTS:: 23 studies were included (17 from sub-Saharan Africa). Meta-analysis of the risk ratios (RR) indicated that HIV-infected women had eight times the risk of a pregnancy-related death compared with HIV-uninfected women (pooled RR: 7.74, 95% CI 5.37-11.16). The excess mortality attributable to HIV among HIV-infected pregnant and postpartum women was 994 per 100,000 pregnant women. We predict that 12% of all deaths during pregnancy and up to one year postpartum are attributable to HIV/AIDS in regions with a prevalence of HIV among pregnant women of 2%. This figure rises to 50% in regions with a prevalence of 15%. CONCLUSION:: The substantial excess of pregnancy-related mortality associated with HIV highlights the importance of integrating HIV and reproductive health services in areas of high HIV prevalence and pregnancy-related mortality.

Calvo-Munoz, I., A. Gomez-Conesa, et al. (2013). "Physical therapy treatments for low back pain in children and adolescents: a meta-analysis." BMC Musculoskelet Disord 14: 55.

ABSTRACT: BACKGROUND: Low back pain (LBP) in adolescents is associated with LBP in later years. In recent years treatments have been administered to adolescents for LBP, but it is not known which physical therapy treatment is the most efficacious. By means of a meta-analysis, the current study investigated the effectiveness of the physical therapy treatments for LBP in children and adolescents. METHODS: Studies in English, Spanish, French, Italian and Portuguese, and carried out by March 2011, were selected by electronic and manual search. Two independent researchers coded the moderator variables of the studies, and performed the effect size calculations. The mean effect size index used was the standardized mean change between the pretest and posttest, and it was applied separately for each combination of outcome measures, (pain, disability, flexibility, endurance and mental health) and measurement type (self-reports, and clinician assessments). RESULTS: Eight articles that met the selection criteria enabled us to define 11 treatment groups and 5 control groups using the group as the unit of analysis. The 16 groups involved a total sample of 334 subjects at the posttest (221 in the treatment groups and 113 in the control groups). For all outcome measures, the average effect size of the treatment groups was statistically and clinically significant, whereas the control groups had negative average effect sizes that were not statistically significant. CONCLUSIONS: Of all the physical therapy treatments for LBP in children and adolescents, the combination of therapeutic physical conditioning and manual therapy is the most effective. The low number of studies and control groups, and the methodological limitations in this meta-analysis prevent us from drawing definitive conclusions in relation to the efficacy of physical therapy treatments in LBP.

Calvo-Munoz, I., A. Gomez-Conesa, et al. (2013). "Prevalence of low back pain in children and adolescents: a meta-analysis." BMC Pediatr 13: 14.

ABSTRACT: BACKGROUND: Low back pain (LBP) is common in children and adolescents, and it is becoming a public health concern. In recent years there has been a considerable increase in research studies that examine the prevalence of LBP in this population, but studies exhibit great variability in the prevalence rates reported. The purpose of this research was to examine, by means of a meta-analytic investigation, the prevalence rates of LBP in children and adolescents. METHODS: Studies were located from computerized databases (ISI Web of Knowledge, MedLine, PEDro, IME, LILACS, and CINAHL) and other sources. The search period extended to April 2011. To be included in the meta-analysis, studies had to report a prevalence rate (whether point, period or lifetime prevalence) of LBP in children and/or adolescents (</= 18 years old). Two independent researchers coded the moderator variables of the studies, and extracted the prevalence rates. Separate meta-analyses were carried out for the different types of prevalence in order to avoid dependence problems. In each meta-analysis, a random-effects model was assumed to carry out the statistical analyses. RESULTS: A total of 59 articles fulfilled the selection criteria. The mean point prevalence obtained from 10 studies was 0.120 (95% CI: 0.09 and 0.159). The mean period prevalence at 12 months obtained from 13 studies was 0.336 (95% CI: 0.269 and 0.410), whereas the mean period prevalence at one week obtained from six studies was 0.177 (95% CI: 0.124 and 0.247). The mean lifetime prevalence obtained from 30 studies was 0.399 (95% CI: 0.342 and 0.459). Lifetime prevalence exhibited a positive, statistically significant relationship with the mean age of the participants in the samples and with the publication year of the studies. CONCLUSIONS: The most recent studies showed higher prevalence rates than the oldest ones, and studies with a better methodology exhibited higher lifetime prevalence rates than studies that were methodologically poor. Future studies should report more information regarding the definition of LBP and there is a need to improve the methodological quality of studies.

Campbell, F., H. O. Dickinson, et al. (2013). "A systematic review of fish-oil supplements for the prevention and treatment of hypertension." Eur J Prev Cardiol 20(1): 107-20.

AIMS: Fish oils are widely believed to promote cardiovascular health by lowering blood pressure (BP) but the evidence supporting this is not conclusive. We aimed to systematically review existing evidence. METHOD: We undertook a systematic review of randomized controlled trials and crossover trials that evaluated the effectiveness of fish-oil supplements. We included trials enrolling adults who were given fish-oil supplements with at least 8 weeks' follow up. Effects on systolic and diastolic BP were assessed using meta-analysis. Meta-regression was undertaken to explore the relationship between dose of fish oil and BP outcomes. RESULTS: We included 17 studies, with a total of 1524 participants. We explored the effects of fish-oil supplements in both normotensive and hypertensive participants with BP 140/85 mmHg at least. Meta-analyses were performed using the inverse-variance method. Data from eight studies in hypertensive participants found a statistically significant reduction in systolic and diastolic BP; 2.56 mmHg (95% CI 0.58 to 4.53) and 1.47 mmHg (95% CI 0.41 to 2.53), respectively. Nine studies in normotensive participants showed a non-significant reduction in both systolic and diastolic BP. Meta-regression showed no significant relationship between dose of fish oil and the effect on BP. CONCLUSION: The small but statistically significant effects of fish-oil supplements in hypertensive participants in this review have important implications for population health and lowering the risk of stroke and ischaemic heart disease. Their modest effects, however, mean that they should not be recommended as an alternative to BP-lowering drugs where guidelines recommend treatment.

Cao, C., C. Manganas, et al. (2013). "Video-assisted thoracic surgery versus open thoracotomy for non-small cell lung cancer: a meta-analysis of propensity score-matched patients." Interact Cardiovasc Thorac Surg 16(3): 244-9.

OBJECTIVES This meta-analysis aimed to compare the perioperative outcomes of video-assisted thoracic surgery (VATS) with open thoracotomy for propensity score-matched patients with early-stage non-small cell lung cancer (NSCLC). METHODS Four relevant studies with propensity score-matched patients were identified from six electronic databases. Endpoints included perioperative mortality and morbidity, individual postoperative complications and duration of hospitalization. RESULTS Results indicate that all-cause perioperative mortality was similar between VATS and open thoracotomy. However, patients who underwent VATS were found to have significantly fewer overall complications, and significantly lower rates of prolonged air leak, pneumonia, atrial arrhythmias and renal failure. In addition, patients who underwent VATS had a significantly shorter length of hospitalization compared with those who underwent open thoracotomy. CONCLUSIONS In view of a paucity of high-level clinical evidence in the form of large, well-designed randomized controlled trials, propensity score matching may provide the highest level of evidence to compare VATS with open thoracotomy for patients with NSCLC. The present meta-analysis demonstrated superior perioperative outcomes for patients who underwent VATS, including overall complication rates and duration of hospitalization.

Cao, C., C. Manganas, et al. (2013). "Drug-eluting stents versus coronary artery bypass graft surgery in left main coronary artery disease: A meta-analysis of early outcomes from randomized and nonrandomized studies." J Thorac Cardiovasc Surg 145(3): 738-47.

OBJECTIVE: The present meta-analysis aimed to compare the short-term safety and efficacy of drug-eluting stents and coronary artery bypass graft surgery for patients with left main coronary artery disease. METHODS: Fourteen relevant studies were identified from 5 electronic databases. End points included mortality, stroke, myocardial infarction, repeat revascularization, and major adverse cardiac and cerebrovascular events. RESULTS: Results indicate that all-cause mortality was similar between drug-eluting stents and coronary artery bypass grafting at 30 days and at follow-up beyond 1 year. Likewise, the incidence of myocardial infarction was similar between drug-eluting stents and coronary artery bypass grafting at 12 months and at follow-up beyond 1 year. However, drug-eluting stents were associated with a lower incidence of all-cause mortality at 12 months and a higher incidence of myocardial infarction at 30 days compared with coronary artery bypass grafting. Drug-eluting stents were consistently associated with a higher incidence of repeat revascularization, whereas coronary artery bypass grafting had a higher incidence of stroke. The incidence of major adverse cardiac and cerebrovascular events was similar between the 2 groups at 30 days but higher for drug-eluting stents at 12 months and beyond. CONCLUSIONS: Patients treated by drug-eluting stents in randomized controlled trials and observational studies in the current literature are often a preselected subgroup with less complex lesions compared with the overall target population. Results drawn from these studies should be viewed with caution. Coronary artery bypass grafting is associated with a lower incidence of major adverse cardiac and cerebrovascular events at 1 year and beyond, and thus should be regarded as the standard of treatment. However, drug-eluting stents may have a role for selected patients with percutaneously amenable left main disease who are poor surgical candidates.

Cao, H., J. C. Auguet, et al. (2013). "Global ecological pattern of ammonia-oxidizing archaea." PLoS One 8(2): e52853.

BACKGROUND: The global distribution of ammonia-oxidizing archaea (AOA), which play a pivotal role in the nitrification process, has been confirmed through numerous ecological studies. Though newly available (ammonia monooxygenase subunit A) gene sequences from new environments are accumulating rapidly in public repositories, a lack of information on the ecological and evolutionary factors shaping community assembly of AOA on the global scale is apparent. METHODOLOGY AND RESULTS: We conducted a meta-analysis on uncultured AOA using over ca. 6,200 archaeal gene sequences, so as to reveal their community distribution patterns along a wide spectrum of physicochemical conditions and habitat types. The sequences were dereplicated at 95% identity level resulting in a dataset containing 1,476 archaeal gene sequences from eight habitat types: namely soil, freshwater, freshwater sediment, estuarine sediment, marine water, marine sediment, geothermal system, and symbiosis. The updated comprehensive phylogeny was composed of three major monophyletic clusters (i.e. , , ) and a non-monophyletic cluster constituted mostly by soil and sediment sequences that we named . Diversity measurements indicated that marine and estuarine sediments as well as symbionts might be the largest reservoirs of AOA diversity. Phylogenetic analyses were further carried out using macroevolutionary analyses to explore the diversification pattern and rates of nitrifying archaea. In contrast to other habitats that displayed constant diversification rates, marine planktonic AOA interestingly exhibit a very recent and accelerating diversification rate congruent with the lowest phylogenetic diversity observed in their habitats. This result suggested the existence of AOA communities with different evolutionary history in the different habitats. CONCLUSION AND SIGNIFICANCE: Based on an up-to-date phylogeny, this analysis provided insights into the possible evolutionary mechanisms and environmental parameters that shape AOA community assembly at global scale.

Cao, J., E. Larocque, et al. (2013). "Associations of the 5-hydroxytryptamine (serotonin) Receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse." Am J Med Genet B Neuropsychiatr Genet 162(2): 169-76.

Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples. (c) 2013 Wiley Periodicals, Inc.

Cao, L., F. Wang, et al. (2013). "PIN1-842G/C and -667T/C polymorphisms are not associated with the susceptibility of Alzheimer's disease: Pooled analysis of epidemiologic studies." Neurosci Lett 535: 100-3.

Associations between PIN1 gene polymorphisms and Alzheimer's disease (AD) risk remain controversial, possibly because single studies often lack sufficient statistical power. In this study, we performed a meta-analysis to evaluate the association of two commonly studied PIN1 polymorphisms, -842G/C and -667T/C, with the risk of AD. Relevant studies were identified from PubMed, EMBASE, and China National Knowledge Infrastructure up to October 2012. Data were available from a total of 7 case-control studies with 2504 cases and 2322 controls. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the association. The results showed no significant association between PIN1-842G/C polymorphism and AD risk in all comparison models (GG vs. GC: OR=0.84, 95%CI=0.61-1.18; GG vs. CC: OR=0.70, 95%CI=0.35-1.41; GC vs. CC: OR=0.81, 95%CI=0.39-1.69; G vs. C: OR=0.89, 95%CI=0.69-1.17; GG vs. GC+CC: OR=0.81, 95%CI=0.56-1.17; GG+GC vs. CC: OR=0.72, 95%CI=0.36-1.45). For the PIN1-667T/C polymorphism, lack of an association was also found. Subgroup analyses by the ethnicity and patients with late-onset AD did not change the results. Conclusively, the present meta-analysis revealed that PIN1 gene polymorphisms (-842G/C and -667T/C) were unlikely to contribute to AD susceptibility.

Cao, S. (2013). "A brief critical comment on a recent meta-analysis." Gene 512(1): 174.

Cao, Y., J. Xu, et al. (2013). "Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: a meta-analysis." Gene 514(2): 105-11.

BACKGROUND: Recurrent pregnancy loss is an important clinical problem. Recently, high-level homocysteine in blood has been considered as a possible cause. Genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) have been proved to be the common hereditary factors of high-level homocysteine. The association between MTHFR polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported but with controversial results. The purpose of present study is to collect and analyze published available data, and evaluate the association between MTHFR polymorphisms and URPL. METHODS: A meta-analysis was performed to examine the association between MTHFR polymorphisms (C677T and A1298C) and URPL. Odds ratio (OR) and its 95% confidence interval (CI) were used in each study of genotype and allele contrast. RESULT(S): MTHFR C677T: The analysis included 3559 URPL cases and 5097 healthy controls. Overall random-effects odds ratios (ORs) were 1.68 (95% CI, 1.32-2.13; P<0.0001) for TT versus total genotypes, 1.35 (95% CI, 1.04-1.76; P=0.0224) for TT and CT genotype combined versus total genotypes and 1.34 (95%CI, 1.13-1.58; P<0.0001) for T versus total alleles. Although significant heterogeneity was found in C677T, it became weaker in the East Asian subgroup and the mixed subgroup when separated by ethnic subgroups. The results showed significant association between MTHFR C677T and URPL in the East Asian subgroup (ORs 2.11 for TT versus total genotype (P=0.0004) and 1.53 for T versus total alleles (P<0.0001)) and in the mixed subgroup (ORs 3.47 for TT versus total genotypes (P<0.0001) and 1.80 for T versus total alleles (P<0.027)), but not in Caucasian subgroup. MTHFR A1298C: The study involved 1163 URPL cases and 1061 healthy controls. Overall random-effects odds ratios (ORs) were 1.37 (95% CI, 0.71-2.67; P=0.3456) for CC versus total genotypes, 1.16 (95%CI, 0.98-1.38; P=0.0833) for CC+AC versus total genotypes and 1.04 (95%CI, 0.84-1.29; P=0.7112) for C versus total alleles. No significant association between MTHFR A1298C polymorphism and URPL was found. CONCLUSIONS: These results indicate a significant association between MTHFR C677T mutation and URPL in the East Asian subgroup and mixed subgroup, but no significance in MTHFR A1298C mutation.

Caplan, G. A. (2013). "A meta-analysis of "hospital in the home"." Med J Aust 198(4): 195-6.

Caplan, L. R. and H. S. Markus (2013). "Antiplatelets vs anticoagulation for dissection: CADISS nonrandomized arm and meta-analysis." Neurology 80(10): 970-1.

The Cervical Artery Dissection in Stroke Study (CADISS-NR) trial concluded that there was no difference in secondary stroke prevention provided by antiplatelet and anticoagulant agents in patients with carotid or vertebral artery dissections. It is important to note that the mean time of treatment after symptom onset was 10.8 days (SD 7.0, range 1-31 days) in this study.

Carayol, M., P. Bernard, et al. (2013). "Psychological effect of exercise in women with breast cancer receiving adjuvant therapy: what is the optimal dose needed?" Ann Oncol 24(2): 291-300.

BACKGROUND: Several meta-analyses have examined the role of exercise interventions in improving psychological outcomes in cancer survivors but most did not focus on adjuvant therapy period and did not investigate the optimal dose of exercise needed. The present meta-analysis examines the impact of exercise interventions delivered at this particular period on fatigue, anxiety, depression, and quality of life (QoL) as well as dose-response relationships between volume of prescribed exercise and these psychological outcomes. MATERIALS AND METHODS: Randomized, controlled trials that proposed an exercise intervention to patients with breast cancer undergoing chemotherapy and/or radiotherapy were systematically identified and coded. Psychological outcomes effect sizes were calculated and analyzed for trends using linear and quadratic regressions. RESULTS: Pooled effects of the 17 included studies revealed improvement for all outcomes, significant for fatigue, depression, and QoL with pooled estimates ranging from 0.2 to 0.5 favoring intervention. Significant inverse associations of the volume of prescribed exercise with fatigue and QoL were observed. CONCLUSIONS: Exercise intervention improved fatigue, depression, and QoL in patients with breast cancer receiving adjuvant therapy. Prescription of relatively low doses of exercise (<12 MET h/week) consisting in approximately 90-120 min of weekly moderate physical exercise seems more efficacious in improving fatigue and QoL than higher doses.

Cardiel, M. H. (2013). "Treat to target strategy in rheumatoid arthritis: Real benefits." Reumatol Clin 9(2): 101-105.

Treating rheumatoid arthritis (RA) with a goal or <<Treat to target>> strategy is a therapeutic proposal taken from cardiovascular and endocrine literature. It proposes that the therapeutic target in RA should be a state of remission, or an alternative goal could be a low disease activity. Rheumatologists should measure and register disease activity in every clinical visit and if the goal has not been reached, therapeutic adjustments should be made. Current evidence from clinical trials and a meta-analysis supports the notion that this strategy has important clinical benefits in patients with early RA when compared with routine care. It is also described that using protocolized treatment offers greater benefits. Recent data from Dutch cohorts is presented showing its successful implementation. A discussion is offered on the need of more studies in established RA.

Carlson, L., K. W. Hatcher, et al. (2013). "Elevated infant mortality rates among oral cleft and isolated oral cleft cases: a meta-analysis of studies from 1943 to 2010." Cleft Palate Craniofac J 50(1): 2-12.

Objective : To review available published literature in order to obtain a more comprehensive assessment of the association between infant mortality and oral clefts, overall and isolated. Design : A wide-ranging search of published studies relating infant mortality rates to oral clefts and congenital malformations was conducted, yielding applicable data sets. Settings of the included studies varied to a limited extent, although all were conducted within high-income countries with superior health indicators. These results were tabulated and meta-analyzed. Random effects odds ratios comparing each data set with its respective population have been used to account for differing settings and specific infant mortality rates. Results : Nine articles with relatable data were included in these meta-analyses. The calculated odds ratio of infant mortality associated with oral cleft cases, including those with associated malformations, was substantial: 9.466 (95% confidence interval, 6.153 to 14.560). Excluding oral cleft cases with associated malformations, the odds ratio, although lower, was still significant: 2.073 (95% confidence interval, 1.390 to 3.092). Conclusions : Compared with the overall population, infants with oral clefts have nine times the odds of dying within the first year of life. Furthermore, even without additional malformations, infants with oral clefts are still twice as likely to die before 1 year of age. Current research points to a substantially higher relative risk of infant mortality among oral cleft cases in developing countries. Additional research is essential to determine the sources of these raised infant mortality rates and possible interventions to decrease them.

Carmona, F. D., M. C. Cenit, et al. (2013). "New insight on the Xq28 association with systemic sclerosis." Ann Rheum Dis.

OBJECTIVE: To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). METHODS: We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. RESULTS: IRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (P(FDR)=4.12x10(-3), OR=1.27, 95% CI 1.09 to 1.47, and P(FDR)=5.26x10(-4), OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (P(FDR)=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF- (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). CONCLUSIONS: Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.

Carmona, F. D., J. E. Martin, et al. (2013). "The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis." PLoS One 8(1): e54419.

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34x10(-8), OR = 1.22, CI 95% = 1.14-1.30; rs2004640: P = 4.60x10(-7), OR = 0.84, CI 95% = 0.78-0.90; rs10488631: P = 7.53x10(-20), OR = 1.63, CI 95% = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04x10(-22), OR = 1.75, CI 95% = 1.56-1.97) better explained the observed association (likelihood P-value = 1.48x10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.

Carotenuto, M., E. Pedone, et al. (2013). "Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction." Sci Rep 3: 1351.

Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.

Carroll, P. J., D. Gibson, et al. (2013). "Surgeon-performed ultrasound at the bedside for the detection of appendicitis and gallstones: systematic review and meta-analysis." Am J Surg 205(1): 102-8.

BACKGROUND: We undertook a systematic review and meta-analysis to compare surgeon-performed ultrasound (SPUS) for suspected appendicitis or gallstone disease to the "gold standard" of pathological examination or radiologist-performed ultrasound (RPUS). DATA SOURCES: MEDLINE, Embase, trial registries, conference proceedings, and article reference lists were searched to identify trials and/or studies comparing SPUS with pathology or RPUS as the reference standard. Data were abstracted from eligible studies to produce 2 x 2 contingency tables, permitting the calculation of pooled sensitivity and specificity values. RESULTS: Eight studies (1,268 patients) evaluated SPUS for appendicitis. For appendicitis, SPUS had a pooled sensitivity of .92 (95% confidence interval [CI], .887-.939) and a pooled specificity of .96 (95% CI, .946-.974). SPUS for gallstones was evaluated in 8 studies (1,019 patients). The pooled sensitivity was .96 (95% CI, .934-.979), and the specificity was .99 (95% CI .983-.998). CONCLUSIONS: SPUS achieves acceptable sensitivity and specificity for both gallstones and appendicitis. However, there was some evidence of heterogeneity. Data regarding cost-effectiveness are lacking.

Carson, J. L. and P. C. Hebert (2013). "Here we go again--blood transfusion kills patients?: comment on "Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis"." JAMA Intern Med 173(2): 139-41.

Cashdollar, J. L. and L. Wymer (2013). "Methods for primary concentration of viruses from water samples: a review and meta-analysis of recent studies." J Appl Microbiol.

Since the beginning of environmental virology in the mid-twentieth century, a key challenge to scientists in the environmental field has been how to collect, isolate and detect pathogenic viruses from water that is used for drinking and/or recreational purposes. Early studies investigated different types of membrane filters, with more sophisticated technologies being developed more recently. The purpose of this study was to look at the current state of the science of methods for the concentration of viruses from water. Several technologies were reviewed, and associated data were included in a meta-analysis which showed that electronegative filters, electropositive filters and ultrafilters are comparable in performance and that significant differences in recovery are due to virus type rather than filter type, water matrix or sample volume. This information is useful, as it will help to determine which method(s) should be used, particularly if there is a specific viral type being targeted for a particular study. In addition, it will be helpful when sampling different environmental water matrices and/or when budget allowance must be taken into consideration. Taken together, this will be useful in performing viral occurrence studies, which ultimately can help ensure safer water for both humans and the environment.

Caslake, R., K. Taylor, et al. (2013). "Age-, gender-, and socioeconomic status-specific incidence of Parkinson's disease and parkinsonism in North East Scotland: The PINE study." Parkinsonism Relat Disord.

There have been few high quality incidence studies of Parkinson's disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I2 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.

Castells, X., R. Cunill, et al. (2013). "Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials." Eur J Clin Pharmacol 69(3): 347-56.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) in adulthood is increasingly diagnosed and treated. Methylphenidate is frequently advocated as a first-line pharmacological treatment. PURPOSE: The aim of our study was to compare all-cause discontinuation rate of methylphenidate and its pharmaceutical presentations with placebo in adults with ADHD. METHODS: This was a systematic review and meta-analysis of randomized controlled trials comparing methylphenidate with placebo in adults with ADHD. All-cause treatment discontinuation was the primary endpoint. The efficacy in reducing ADHD symptoms and safety were the secondary endpoints. RESULTS: Twelve studies (2,496 patients) met the inclusion criteria. Four racemic methylphenidate and one dexmethylphenidate presentations were investigated. The rate of all-cause treatment discontinuation was greater with methylphenidate than with placebo, but this difference was not statistically significant [odds ratio (OR) 1.19, 95 % confidence interval (95 % CI) 0.82-1.74, P = 0.37, I (2) = 64 %] This finding reached the conventional threshold of statistical significance after one outlier study was excluded (OR 1.44, 95 % CI 1.14-1.82, P = 0.002, I (2) = 0). Methylphenidate was more efficacious than placebo for reducing ADHD symptoms and it was associated with a higher proportion of patients dropping out due to adverse effects. CONCLUSIONS: Despite reducing ADHD symptoms, methylphenidate showed no advantage over placebo in terms of treatment discontinuation. More attention should be given in the future to the endpoint "all-cause treatment discontinuation" when making regulatory decisions and developing clinical guidelines involving the treatment of ADHD in adulthood.

Catala-Lopez, F. (2013). "Safety of aprotinin in adult cardiac surgery: revisiting the validity of a mixed-treatment comparison meta-analysis." J Thorac Cardiovasc Surg 145(2): 610.

Catala-Lopez, F., M. Ridao, et al. (2013). "Cost-effectiveness of pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: Qualitative synthesis of scientific evidence." Rev Psiquiatr Salud Ment.

OBJECTIVE: To describe the cost-effectiveness analyses of medications launched in Spain for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. MATERIAL AND METHODS: Systematic review of the literature without meta-analysis. A search was made in, PubMed/MEDLINE, SCOPUS, databases of the Centre for Reviews and Dissemination, and the websites of technology assessment agencies from Canada, the United Kingdom and the Spanish Platform AUnETS. Only full economic evaluations were included, considering at least methylphenidate or atomoxetine as pharmacological treatment alternatives in children and/or adolescents with ADHD. RESULTS: Eleven studies published in 9 articles or reports were included. The most frequent characteristics were: cost-utility analysis (82%), health system perspective (82%), short-term horizon (91%), and private funding (50%). Methylphenidate was included in all studies, and atomoxetine in 4 studies. Methylphenidate and atomoxetine are cost-effective alternatives compared to placebo or no treatment, although incremental cost-effectiveness ratios are variable. The few direct treatment-comparisons between methylphenidate and atomoxetine provided contradictory and potentially biased results. CONCLUSIONS: The pharmacological treatment of ADHD in children and adolescents, with the reservations arising from the generalization of results to different settings, is probably cost-effective in the short term. The existing studies do not allow the relative efficiency of different treatments to be established, either in the long-term treatment or in patient subgroups with specific characteristics or comorbidities.

Catala-Lopez, F., G. Sanfelix-Gimeno, et al. (2013). "Efficacy of osteoporosis therapies in a network meta-analysis with indirect comparisons: many concerns for new tools of evidence synthesis?" Osteoporos Int.

Catala-Lopez, F. and A. Tobias (2013). "[Clinical evidence synthesis and network meta-analysis with indirect-treatment comparisons]." Med Clin (Barc) 140(4): 182-7.

Celar, A., M. Schedlberger, et al. (2013). "Systematic review on self-ligating vs. conventional brackets: initial pain, number of visits, treatment time." J Orofac Orthop 74(1): 40-51.

OBJECTIVE: Meta-analysis of differences between conventional and self-ligating brackets concerning pain during tooth movement, number of patient visits, total treatment duration, and ligation times. MATERIALS AND METHODS: Online search in Medline, Embase, and Central focused on randomized clinical trials and controlled clinical studies published between 1996 and 2012. RESULTS: Four studies on pain met our inclusion criteria, two on the number of appointments, two on overall treatment time but none on ligation times. Pain levels did not differ significantly between patients treated with conventional or self-ligating brackets after 4 h, 24 h, 3 and 7 days. The number of appointments and total treatment times revealed no significant differences between self-ligating and conventional brackets. CONCLUSION: The lack of significant overall effects apparent in this meta-analysis contradicts evidence-based statements on the advantages of self-ligating brackets over conventional ones regarding discomfort during initial orthodontic therapy, number of appointments, and total treatment time. Due to the limited number of studies included, further randomized controlled clinical trials are required to deliver more data and to substantiate evidence-based conclusions on differences between the two bracket types considering orthodontic pain, number of visits, treatment, and ligation times.

Celeste, R. K. (2013). "Oxygenating Agents may Inhibit Tooth Staining Effect of Chlorhexidine." J Evid Based Dent Pract 13(1): 9-10.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effect of an oxygenating agent on chlorhexidine-induced extrinsic tooth staining: a systematic review. van Maanen-Schakel N, Slot D, Bakker E, Van der Weijden G. Int J Dent Hyg 2012 May 17;10(3):198-208. REVIEWER: Roger Keller Celeste, DDS, MSc, PhD PURPOSE/QUESTION: To review clinical trials on the effect of mouthwashes with chlorhexidine alone compared those with chlorhexidine and an oxygenating agent on tooth staining SOURCE OF FUNDING: No external source of funding (self-funded) TYPE OF STUDY/DESIGN: Systematic review with meta-analysis LEVEL OF EVIDENCE: Level 1: Good-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade A: Consistent, good-quality patient-oriented evidence.

Celio, L., E. Bonizzoni, et al. (2013). "Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials." Support Care Cancer 21(2): 565-73.

PURPOSE: Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy. METHODS: Chemo-naive breast cancer patients randomized to receive palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n = 200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3 (n = 205), were included in the analysis. The primary endpoint was complete response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period. The effect of the 1-day regimen and age (<50 and >/= 50 years) was investigated by a meta-analysis of individual patient data. RESULTS: Younger patients comprised 43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the pooled sample received the AC combination. There were no between-treatment differences in CR rate according to age during all observation periods. In the 1-day regimen group, 55.2 % of younger patients achieved overall CR compared with 54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients achieved overall CR compared with 58.7 % of older patients. In the adjusted analysis, younger age was not associated with overall CR to treatment (risk difference, -3.1 %; 95 % CI, -13.0 to 6.7 %; P = 0.533). CONCLUSIONS: These results provide evidence that, irrespective of age, the dexamethasone-sparing regimen is not associated with a significant loss in overall anti-emetic protection in women undergoing AC-containing chemotherapy.

Centers for Disease, C. and Prevention (2013). "Early estimates of seasonal influenza vaccine effectiveness--United States, January 2013." MMWR Morb Mortal Wkly Rep 62(2): 32-5.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged >/=6 months. Each season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended acute respiratory infection (ARI). This season, early data from 1,155 children and adults with ARI enrolled during December 3, 2012-January 2, 2013 were used to estimate the overall effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. After adjustment for study site, but not for other factors, the estimated vaccine effectiveness (VE) was 62% (95% confidence intervals [CIs] = 51%-71%). This interim estimate indicates moderate effectiveness, and is similar to a summary VE estimate from a meta-analysis of randomized controlled clinical trial data; final estimates likely will differ slightly. As of January 11, 2013, 24 states and New York City were reporting high levels of influenza-like illness, 16 states were reporting moderate levels, five states were reporting low levels, and one state was reporting minimal levels. CDC and the Advisory Committee on Immunization Practices routinely recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating. Persons aged >/=6 months who have not yet been vaccinated this season should be vaccinated. However, these early VE estimates underscore that some vaccinated persons will become infected with influenza; therefore, antiviral medications should be used as recommended for treatment in patients, regardless of vaccination status. In addition, these results highlight the importance of continued efforts to develop more effective vaccines.

Cerrato, E., F. D'Ascenzo, et al. (2013). "Cardiac dysfunction in pauci symptomatic human immunodeficiency virus patients: a meta-analysis in the highly active antiretroviral therapy era." Eur Heart J.

AimsHuman immunodeficiency virus infection (HIV) has been associated with cardiac dysfunction that, if present, can negatively affect morbidity and mortality of HIV-infected patients. Unfortunately, many of the studies on this topic were performed before the highly active antiretroviral therapy (HAART) was established. Thus, we performed a comprehensive meta-analysis to critically appraise the incidence of cardiac dysfunction in HIV-infected pauci symptomatic patients.Methods and resultsMedline, Cochrane Library, and Biomed Central were systematically screened for studies reporting on systolic and/or diastolic dysfunctions in HIV pauci-symptomatic patients. Baseline treatment and cardiac imaging data were appraised and pooled with random effect methods computing summary. At pooled analysis, including a total of 2242 patients from 11 studies, an overall average incidence of traditional cardiovascular risk factors was observed, while a low rate of previous coronary artery disease was reported. Incidence of systolic and diastolic left ventricular dysfunction was 8.33% (95% CI: 2.20-14.25) and 43.38% (95% CI: 31.73-55.03), respectively. Diastolic dysfunction was graded as first [31.85% (95% CI: 24.85-43.73)], second [8.53% (95% CI: 2.12-14.93)], and third degree [3.02% (95% CI: 1.78-4.27)]. At multivariate analysis, a high sensitivity C-reactive protein level >5 mg/L, active tobacco smoking and previous history of myocardial infarction were predictors of left ventricular systolic dysfunction [odd ratio 1.70 (95% CI: 1.03-2.77); 1.57 (95% CI: 1.03-2.34); and 15.90 (95% CI: 1.94-329.00), respectively]. Hypertension (OR = 2.30; 95% CI: 1.20-4.50) and older age (OR = 2.50 per 10 years increase; 95% CI: 1.70-3.60) were predictors of left ventricular diastolic dysfunction (Figure 3).ConclusionsSystolic and diastolic dysfunction represent a common finding in pauci symptomatic HIV-infected patients, regardless to HAART.

Chae, Y., D. S. Chang, et al. (2013). "Inserting needles into the body: a meta-analysis of brain activity associated with acupuncture needle stimulation." J Pain 14(3): 215-22.

Acupuncture is a therapeutic treatment that is defined as the insertion of needles into the body at specific points (ie, acupoints). Advances in functional neuroimaging have made it possible to study brain responses to acupuncture; however, previous studies have mainly concentrated on acupoint specificity. We wanted to focus on the functional brain responses that occur because of needle insertion into the body. An activation likelihood estimation meta-analysis was carried out to investigate common characteristics of brain responses to acupuncture needle stimulation compared to tactile stimulation. A total of 28 functional magnetic resonance imaging studies, which consisted of 51 acupuncture and 10 tactile stimulation experiments, were selected for the meta-analysis. Following acupuncture needle stimulation, activation in the sensorimotor cortical network, including the insula, thalamus, anterior cingulate cortex, and primary and secondary somatosensory cortices, and deactivation in the limbic-paralimbic neocortical network, including the medial prefrontal cortex, caudate, amygdala, posterior cingulate cortex, and parahippocampus, were detected and assessed. Following control tactile stimulation, weaker patterns of brain responses were detected in areas similar to those stated above. The activation and deactivation patterns following acupuncture stimulation suggest that the hemodynamic responses in the brain simultaneously reflect the sensory, cognitive, and affective dimensions of pain. PERSPECTIVE: This article facilitates a better understanding of acupuncture needle stimulation and its effects on specific activity changes in different brain regions as well as its relationship to the multiple dimensions of pain. Future studies can build on this meta-analysis and will help to elucidate the clinically relevant therapeutic effects of acupuncture.

Challis, S., O. Nielssen, et al. (2013). "Systematic meta-analysis of the risk factors for deliberate self-harm before and after treatment for first-episode psychosis." Acta Psychiatr Scand.

OBJECTIVE: Attempted suicide and deliberate self-injury can occur before or after presentation with a first-episode of psychosis. The aim of the study is to identify the factors associated with suicide attempts or deliberate self-injury before and after treatment for first-episode psychosis. METHOD: A systematic review and meta-analysis of controlled studies of factors associated with either suicide attempts or deliberate self-injury, referred to here as deliberate self-harm (DSH). RESULTS: The pooled proportion of patients who reported DSH prior to treatment for first-episode psychosis was 18.4% (95% Confidence Interval (CI) 14.4-23.3, N = 18 studies, I(2) = 93.8). The pooled proportion of patients with DSH during the period of untreated psychosis was 9.8%, (95% CI 6.7-14.2, N = 5 studies, I(2) = 58.9). The pooled proportion of patients committing DSH during periods of follow up of between 1 and 7 years was 11.4%, (95% CI, 8.3-15.5, N = 13 studies, I(2) = 89.2). Categorical factors associated with an increased risk of DSH were a prior history of DSH (OR = 3.94), expressed suicide ideation (OR = 2.34), greater insight (OR = 1.64), alcohol abuse (OR = 1.68) and substance use (OR = 1.46). Continuous variables associated with an increased risk of DSH were younger age of onset (Standardized Mean Difference (SMD) = -0.28), younger age at first treatment (SMD = -0.18), depressed mood (SMD = 0.49) and the duration of untreated psychosis (SMD = 0.20). Depressed mood and substance use were associated with DSH both before and after treatment, negative symptoms were associated with DSH after treatment but not before treatment. Positive symptoms and social and global functioning were not associated with DSH. Younger age and the duration of untreated psychosis were associated with DSH before treatment but not after treatment. CONCLUSION: Earlier treatment of first-episode psychosis and successful treatment of depression and substance use could prevent some episodes of DSH and might reduce suicide mortality in early psychosis.

Chambrone, L., A. M. Foz, et al. (2013). "Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate." J Clin Periodontol.

AIM: The aim of this systematic review (SR) was to evaluate the association between periodontitis and chronic kidney disease (CKD) and the effect of periodontal treatment (PT) on the estimated glomerular filtration rate (eGFR). METHODS: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched up to and including September 30, 2012 to observational (S1) and interventional (S2) studies on the association of periodontitis with CKD. Studies were considered eligible for inclusion if they reported the eGFR. Search was conducted by two independent reviewers. The methodological quality of the observational studies was assessed using the Newcastle-Ottawa Scale (NOS) adapted for this review, and the Cochrane's Collaboration risk of bias assessment tool. A random-effects odds-ratio meta-analysis was conducted to estimate the degree of association between periodontitis and CKD. RESULTS: Search strategy identified 2456 potentially eligible articles, of which four cross-sectional, one retrospective, and three interventional studies were included. Four S1, 80.0% reported some degree of association between periodontitis and CKD. Similarly, such an outcome was supported by pooled estimates (OR: 1.65, 95% Confidence Interval: 1.35, 2.01, p < 0.00001, chi(2) = 1.70, I(2 ) = 0%). All interventional studies found positive outcomes related to treatment. CONCLUSION: There is quite consistent evidence to support the positive association between periodontitis and CKD, as well as the positive effect of PT on eGFR.

Chamorro, A. J., M. Marcos, et al. (2013). "Association of allelic variants of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase with thrombosis or ocular involvement in Behcet's disease: A systematic review and meta-analysis." Autoimmun Rev 12(5): 607-16.

Thrombosis is frequent in patients with Behcet's disease (BD), although the exact cause remains uncertain. Some single nucleotide polymorphism (SNP) (G1691A in factor V gene, also called factor V Leiden [FVL], G20210A in prothrombin gene and C677T in methyltetrahydrofolate reductase [MTHFR] gene) have been associated with thrombosis and ocular involvement in BD with controversial results. AIM: To assess the effects of FVL, prothrombin and MTHFR SNP variants in patients with BD and thrombosis and ocular involvement by means of a systematic review and meta-analysis. METHODS: We retrieved studies analyzing the genotype of the above-mentioned polymorphism among patients with BD. A meta-analysis was conducted in a random effects model and calculations of odds ratio (OR) and confidence intervals (CI) were done. Sensitivity analysis and tests for heterogeneity of the results were performed. RESULTS: 27 previous studies analyzed the association of BD and thrombosis with the FVL, prothrombin and MTHFR polymorphisms. A significant association was found between the possession of the AA or GA genotypes of FVL polymorphism among patients with BD and the presence of any thrombosis (OR=2.51; 95% CI: 1.68, 3.74; P<0.00001). In addition, a significant association was found between the possession of the GA or AA genotypes and the presence of BD (OR=2.67; 95% CI: 1.93. 3.72; P<0.00001) when cases with BD and healthy controls were compared. This association was not found when studies from Turkey were excluded. No association was found between prothrombin and MTHFR SNPs and thrombosis in BD, and no association between any SNP and ocular involvement was shown either. CONCLUSIONS: Factor V Leiden could be responsible for some thrombotic events in at least Turkish patients. However, this relationship has to be demonstrated from a pathogenic point of view.

Champaneria, R., L. Shah, et al. (2013). "Analgesic effectiveness of transversus abdominis plane blocks after hysterectomy: a meta-analysis." Eur J Obstet Gynecol Reprod Biol 166(1): 1-9.

To determine the effectiveness of transversus abdominis plane blocks in gynecological surgery by systematic review and meta-analysis. Embase, MEDLINE and the Cochrane Library (CENTRAL) bibliographic databases were searched using a Cochrane Library search strategy modified for gynecological surgery. We included randomized controlled trials comparing transversus abdominis plane block with no block or placebo block. We retrieved 681 citations from which we included five published studies (225 randomized participants) which fulfilled our inclusion criteria, and identified a further six ongoing studies. Quality was assessed across six risk of bias domains: randomization sequence generation, allocation concealment, blinding, missing outcome data, selective reporting and other biases. Data were meta-analyzed where possible and presented as mean differences with 95% confidence intervals. Study quality was moderate. Compared with no block or saline placebo, transversus abdominis plane block provided significantly less postoperative pain at rest on a 10 cm visual analog scale at 2h (mean difference -2.14 cm, 95% confidence interval (CI) -3.57 to -0.71) but not at 24h postoperatively (-0.52 cm, 95% CI -1.49 to 0.45). Pain on movement showed similar results. Transversus abdominis plane block resulted in significantly less postoperative requirement for morphine use at 24h (-11.76 mg, 95% CI -18.77 to -4.75) but not at 48 h (-16.01 mg, 95% CI -39.40 to 7.39). Evidence exists for the short-term efficacy (within 24 h) of transversus abdominis plane blocks during hysterectomy in terms of reported pain and morphine consumption, which may not be sustained at 48 h. Updates to this review should be undertaken periodically, and until further robust evidence is available, anesthetists should not rush to adopt this procedure into routine practice.

Chan, C. C., Y. Y. Chan, et al. (2013). "Systematic review and meta-analysis of the use of tranexamic acid in tonsillectomy." Eur Arch Otorhinolaryngol 270(2): 735-48.

Post-tonsillectomy haemorrhage is a serious complication that can lead to death despite the fact that tonsillectomy is one of the commonest procedures performed in otolaryngology. Post-operative haemorrhage can be reduced by a potent antifibrinolytic agent such as tranexamic acid (TXA). This systematic review aims to evaluate the role of TXA in tonsillectomy. Searches were performed on MEDLINE, EMBASE, Web of Science and the Cochrane Library. Study selection, data extraction and quality assessment were conducted independently by two reviewers. Mean difference (MD) in volume of blood loss was calculated with 95 % confidence interval (CI). Risk ratios (RR) with 95 % CI were computed using random effects for the risk of post-tonsillectomy haemorrhage. This review identified and included a total of seven studies. Two studies (n = 180) compared the effects of TXA on volume of blood loss. Meta-analysis of these studies showed a significant decrease in the mean blood loss of 32.72 ml (95 % CI -42.66 to -22.78, p < 0.00001). Five studies (n = 1,670) compared the number of patients with post-tonsillectomy haemorrhage between TXA and control groups. TXA does not reduce the number of patients with post-tonsillectomy haemorrhage significantly (RR = 0.51, 95 % CI 0.25 to 1.07, p = 0.08). TXA led to a significant reduction of tonsillectomy blood loss volume but had no impact on the rate of patients with post-tonsillectomy haemorrhage. This systematic review demonstrated that most studies were conducted before 1980; therefore, a new, large and well-designed randomised controlled trial is needed to investigate the risks and benefits of TXA.

Chan, D. S., T. D. Reid, et al. (2013). "Systematic review and meta-analysis of the influence of circumferential resection margin involvement on survival in patients with operable oesophageal cancer." Br J Surg 100(4): 456-64.

BACKGROUND: The prognostic role and definition of circumferential resection margin (CRM) involvement in operable oesophageal cancer remain controversial. The College of American Pathologists (CAP) and Royal College of Pathologists (RCP) define CRM involvement as tumour found at the cut resection margin and within 1 mm of the cut margin respectively. This systematic review and meta-analysis was performed to determine the influence of CRM involvement on survival in operable oesophageal cancer. METHODS: PubMed, MEDLINE and the Cochrane Library (January 1990 to June 2012) were searched for studies correlating CRM involvement with 5-year mortality. Statistical analysis of dichotomous variables was performed using the odds ratio (OR) as the summary statistic. RESULTS: Fourteen studies involving 2433 patients with oesophageal cancer who had undergone potentially curative oesophagectomy were analysed. Rates of CRM involvement were 15.3 per cent (173 of 1133) and 36.5 per cent (889 of 2433) according to the CAP and RCP criteria respectively. Overall 5-year mortality rates were significantly higher in patients with CRM involvement compared with CRM-negative patients according to both CAP (OR 4.02, 95 per cent confidence interval (c.i.) 2.25 to 7.20; P < 0.001) and RCP (OR 2.52, 1.96 to 3.25; P < 0.001) criteria. CRM involvement between 0.1 and 1 mm was associated with a significantly higher 5-year mortality rate than CRM-negative status (involvement more than 1 mm from CRM) (OR 2.05, 95 per cent c.i. 1.41 to 2.99; P < 0.001). CONCLUSION: CRM involvement is an important predictor of poor prognosis. CAP criteria differentiate a higher-risk group than RCP criteria, but overlook a patient group with similar poor outcomes. Copyright (c) 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Chan, E. W., Y. He, et al. (2013). "Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs." Obes Rev.

Lorcaserin is a new anti-obesity drug recently approved by US Food and Drug Administration. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the association of lorcaserin therapy with weight loss and adverse events in obese adults (18-65 years old). Weight loss of 3.23 kg (95% confidence interval [CI]: 2.70, 3.75) and body mass index reduction of 1.16 kg m(-2) (95% CI: 0.98, 1.34) was observed compared with placebo in RCTs of 1 year duration. The use of lorcaserin for 8 and 12 weeks reduced weight of 1.60 kg (95% CI: 0.34, 2.86) and 2.9 kg (95% CI: 2.2, 3.5), respectively. In comparison to placebo, lorcaserin decreased waist circumference, blood pressure, total cholesterol, low-density lipoprotein-cholesterol and triglycerides, however did not statistically affect heart rate or high-density lipoprotein-cholesterol. Headache, nausea and dizziness were found to be significantly higher in the patients receiving lorcaserin than patients receiving placebo, whereas diarrhoea is no more likely than in patients receiving placebo. In conclusion, lorcaserin achieves modest weight loss and appears to be well tolerated. Clinical and pharmacovigilance studies with longer study duration are needed to inform of the long-term efficacy and safety of lorcaserin.

Chan, K., R. S. Patel, et al. (2013). "Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: a collaborative meta-analysis." J Am Coll Cardiol 61(9): 957-70.

OBJECTIVES: This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD. BACKGROUND: Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. METHODS: We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. RESULTS: We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. CONCLUSIONS: The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.

Chan, M. F., I. Mattar, et al. (2013). "Investigating factors that have an impact on nurses' performance of patients' conscious level assessment: a systematic review." J Nurs Manag 21(1): 31-46.

AIM: To identify factors that have an impact on nurses' performance of patients' conscious level assessment. BACKGROUND: There is a need for nurses to accurately assess a patient's conscious level to detect neurological changes and initiate prompt action. METHODS: Nine databases were systematically searched (1990-February 2010) to review experimental, cohort, case control, cross-sectional and descriptive studies that addressed factors which affected nurses' performance of patient conscious level assessment. Participants in the studies reviewed were nursing staff. The Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument was used for quality assessment. RESULTS: Eleven studies were analysed in this review. Knowledge and experience were found to be the most significant factors in determining nurses' performance of patient conscious level assessment. Formal training was found to be effective in improving assessment skills and experience greatly affected the accuracy of assessment. CONCLUSION: Knowledge and experience are the most significant factors on nurses' performance of consciousness level assessment. Implications for nursing management Formal training is needed on a continual basis to maintain skills in consciousness level assessment, and nurses who are more experienced in the use of assessment should mentor those that are less experienced.

Chan, R. J. (2013). "Response to "Topical agent therapy for prevention and treatment of radiodermatitis: a meta-analysis"." Support Care Cancer.

Chang, K. H., J. P. Burke, et al. (2013). "Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis." Int J Colorectal Dis 28(3): 287-93.

PURPOSE: Acute severe colitis affects 25 % of patients with ulcerative colitis (UC). Up to 30-40 % of these patients are resistant to intensive steroid therapy and therefore require rescue therapy to prevent emergent colectomy. Data comparing rescue therapy using infliximab and cyclosporine are limited and equivocal. This study evaluates the outcomes of UC patients receiving infliximab or cyclosporine as rescue therapy in acute severe steroid-refractory exacerbations. METHODS: Electronic databases (PubMed, EMBASE, and Cochrane database) were searched for studies directly comparing infliximab and cyclosporine in UC, and references of included studies were screened. Two independent reviewers identified relevant studies and extracted data. Meta-analyses were performed using the random effect model. Outcome measures included 3- and 12-month colectomy rates, adverse drug reactions, and postoperative complications. RESULTS: Six retrospective cohort studies describing 321 patients met the inclusion criteria. The meta-analysis did not show significant differences between infliximab and cyclosporine in the 3-month colectomy rate (odds ratio (OR) = 0.86, 95 % confidence interval (CI) = 0.31-2.41, p = 0.775), in the 12-month colectomy rate (OR = 0.60, 95 % CI = 0.19-1.89, p = 0.381), in adverse drug reactions (OR = 0.76, 95 % CI = 0.34-1.70, p = 0.508), and in postoperative complications (OR = 1.66, 95 % CI = 0.26-10.50, p = 0.591). Funnel plot revealed no publication bias. CONCLUSIONS: Infliximab and cyclosporine are comparable when used as rescue therapy in acute severe steroid-refractory UC. Randomized trials are required to further evaluate these agents.

Chang, L. J., T. Yarkoni, et al. (2013). "Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference." Cereb Cortex 23(3): 739-49.

Recent work has indicated that the insula may be involved in goal-directed cognition, switching between networks, and the conscious awareness of affect and somatosensation. However, these findings have been limited by the insula's remarkably high base rate of activation and considerable functional heterogeneity. The present study used a relatively unbiased data-driven approach combining resting-state connectivity-based parcellation of the insula with large-scale meta-analysis to understand how the insula is anatomically organized based on functional connectivity patterns as well as the consistency and specificity of the associated cognitive functions. Our findings support a tripartite subdivision of the insula and reveal that the patterns of functional connectivity in the resting-state analysis appear to be relatively conserved across tasks in the meta-analytic coactivation analysis. The function of the networks was meta-analytically "decoded" using the Neurosynth framework and revealed that while the dorsoanterior insula is more consistently involved in human cognition than ventroanterior and posterior networks, each parcellated network is specifically associated with a distinct function. Collectively, this work suggests that the insula is instrumental in integrating disparate functional systems involved in processing affect, sensory-motor processing, and general cognition and is well suited to provide an interface between feelings, cognition, and action.

Chang, M. C., J. H. Chen, et al. (2013). "Accuracy of whole-body FDG-PET and FDG-PET/CT in M staging of nasopharyngeal carcinoma: a systematic review and meta-analysis." Eur J Radiol 82(2): 366-73.

BACKGROUND: A meta-analysis was conducted to evaluate the accuracy of whole-body positron emission tomography (PET) or PET/CT in M staging of nasopharyngeal carcinoma (NPC). METHODS: Through a search of relevant English language studies from October 1996 to September 2011, pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and summary receiver operating characteristic (SROC) curves of whole-body PET or PET/CT in M staging of NPC were calculated. RESULTS: Three PET and 5 PET/CT studies were identified. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG-PET or PET/CT were 0.83 (95% confidence interval [CI], 0.77-0.88), 0.97 (95% CI, 0.95-0.98), 23.38 (95% CI, 16.22-33.69), and 0.19 (95% CI, 0.13-0.25), respectively. The area under curve was 0.9764 and Q* index estimate was 0.9307 for FDG-PET or PET/CT. CONCLUSION: Current evidence confirms the good diagnostic performance of the whole-body FDG-PET or PET/CT in M staging of NPC.

Chang, W. W., L. Zhang, et al. (2013). "Meta-analysis of the transforming growth factor-beta1 polymorphisms and susceptibility to Alzheimer's disease." J Neural Transm 120(2): 353-60.

The association between transforming growth factor-beta1 (TGF-beta1) gene polymorphisms and Alzheimer's disease (AD) risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-beta1 polymorphisms and AD risk, we conducted a meta-analysis of all available case-control studies relating the T869C and/or C-509T polymorphisms of the TGF-beta1 gene to the risk of developing AD. Eligible articles were identified by search of databases including Pub Med, Web of Science, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and the Wan Fang (Chinese) for the period up to March 2012. Finally, a total of 14 articles were identified, 10 with 1,657 cases and 6,971 controls for T869C polymorphism and 8 with 2,618 cases and 7,473 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity. With respect to T869C and C-509T polymorphism, the combined results showed that there were no significant differences in genotype distribution between AD and control based on all studies. When stratifying for the race, there were also no statistically significant differences in genotype distribution between AD and controls. This meta-analysis did not provide an evidence of confirming association between the T869C and/or C-509T polymorphisms of the TGF-beta1 gene and AD.

Chang, X. and J. Wu (2013). "Effects of luteal estradiol pre-treatment on the outcome of IVF in poor ovarian responders." Gynecol Endocrinol 29(3): 196-200.

Background: In view of the discrepancies about the luteal estradiol treatment before stimulation protocols having some potential advantages compared with the standard protocols in poor ovarian responders undergoing IVF, a meta-analysis of the published data was performed to compare the efficacy of the luteal estradiol pre-treatment protocols in IVF poor response patients. Methods: We searched for all published articles. The searches yielded 32 articles, from which seven studies met the inclusion criteria. We performed this meta-analysis involving 450 IVF patients in luteal estradiol pre-treatment protocol group and 606 patients in standard protocol group. Results: The luteal estradiol protocol resulted in a significantly higher duration of stimulation compared with the standard protocol. In addition, the number of oocytes retrieved and mature oocytes retrieved were significantly higher in the luteal estradiol protocols than those in the standard protocols. The cycle cancellation rate (CCR) in the luteal estradiol protocols was lower than the standard protocols. Moreover, no significant difference was found in the clinical pregnancy rate (CPR). Conclusions: The addition of the estradiol in the luteal phase preceding IVF in poor responders improved IVF cycle outcomes, including increasing the number of oocytes retrieved and mature oocytes retrieved and decreasing the CCR.

Chang, X., Y. Zhang, et al. (2013). "Health effects of exposure to nano-TiO2: a meta-analysis of experimental studies." Nanoscale Res Lett 8(1): 51.

ABSTRACT: The paper is aimed to investigate the toxicity of nano-TiO2 and its potential harmful impact on human health using meta-analysis of in vitro and short-time animal studies. Data were retrieved according to included and excluded criteria from 1994 to 2011. The combined toxic effects of nano-TiO2 were calculated by the different endpoints by cell and animal models. From analysis of the experimental studies, more than 50% showed positive statistical significance except the apoptosis group, and the cytotoxicity was in a dose-dependent but was not clear in size-dependent manner. Nano-TiO2 was detained in several important organs including the liver, spleen, kidney, and brain after entering the blood through different exposure routes, but the coefficient of the target organs was altered slightly from animal models. It is possible that nano-TiO2 can induce cell damage related to exposure size and dose. Further studies will be needed to demonstrate that nanoparticles have toxic effects on human body, especially in epidemiological studies.

Chao, G. Q. and S. Zhang (2013). "A Meta-analysis of the Therapeutic Effects of Amitriptyline for Treating Irritable Bowel Syndrome." Intern Med 52(4): 419-24.

Objective We aimed to evaluate the efficacy of amitriptyline as a therapeutic option for irritable bowel syndrome (IBS) through a meta-analysis of randomized controlled trials. Methods For the years from 1966 until May 2012, PubMed, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched for double-blind, placebo-controlled trials investigating the efficacy of amitriptyline in the management of IBS. Results Four randomized, placebo-controlled clinical trials met our criteria and were included in the meta-analysis. The pooled relative risk for clinical improvement with amitriptyline therapy was 4.18 (95% CI: 2.00 to 8.77, p=0.0001). Conclusion It was thus concluded that amitriptyline exhibits a clinically and statistically significant control of IBS symptoms.

Chapelle, C., S. Quenet, et al. (2013). "Antipsychotics: a real or confounding risk factor for venous thromboembolism?" Pharmacopsychiatry 46(1): 36-7.

In a meta-analysis of case-control studies, Zhang et al. (2011) found an increased risk of venous thromboembolic events (VTE) in patients exposed to antipsychotics (OR=2.39 [1.71-3.35]). Our updated meta-analysis including the 2 available cohort studies, recognized as a more relevant type of observational study, showed a weaker, but still strong association (OR=1.84 [1.39; 2.44]). In view of the lack of data on the confirmed risk factors for VTE in existing studies, prospective studies including adjustment for these risk factors are warranted to confirm this association and to assess the benefit/risk ratio of antipsychotics in high-risk patients.

Charidimou, A., P. Kakar, et al. (2013). "Cerebral microbleeds and the risk of intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: systematic review and meta-analysis." J Neurol Neurosurg Psychiatry 84(3): 277-80.

BACKGROUND: Intracerebral haemorrhage (ICH) remains the most devastating yet unpredictable complication of intravenous thrombolysis for acute ischaemic stroke. We performed a systematic review and meta-analysis, to assess whether the presence of cerebral microbleeds (CMBs) on prethrombolysis MRI scans is associated with an increased risk of ICH. METHODS: We searched PubMed for studies assessing ICH risk in patients with acute ischaemic stroke treated with thrombolysis, in relation to the presence of pre-treatment CMBs. RESULTS: We identified five studies including 790 patients and pooled data in a meta-analysis. The CMB (+) versus CMB (-) groups were not significantly different in age, gender or stroke severity. The overall prevalence of CMBs was 135/790 (17.1%). Amongst patients with CMBs, 10/135 (7.4%) experienced a symptomatic ICH after thrombolysis, compared to 29/655 (4.4%) patients without CMBs. The pooled relative risk of ICH was 1.90 (95% CI 0.92 to 3.93; p=0.082). CONCLUSIONS: The available evidence does not demonstrate a statistically significant increased risk of symptomatic ICH after thrombolysis for ischaemic stroke in patients with CMBs. However, in view of the methodological limitations of the studies included, the clinical relevance of any potential hazard associated with CMBs remains uncertain. Further studies are warranted to evaluate whether the risk of ICH might outweigh the benefit of thrombolysis, especially in patients with multiple lobar CMBs suggestive of cerebral amyloid angiopathy.

Chatterjee, S., G. Biondi-Zoccai, et al. (2013). "Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis." BMJ 346: f55.

OBJECTIVE: To clarify whether any particular beta blocker is superior in patients with heart failure and reduced ejection fraction or whether the benefits of these agents are mainly due to a class effect. DESIGN: Systematic review and network meta-analysis of efficacy of different beta blockers in heart failure. DATA SOURCES: CINAHL(1982-2011), Cochrane Collaboration Central Register of Controlled Trials (-2011), Embase (1980-2011), Medline/PubMed (1966-2011), and Web of Science (1965-2011). STUDY SELECTION: Randomized trials comparing beta blockers with other beta blockers or other treatments. DATA EXTRACTION: The primary endpoint was all cause death at the longest available follow-up, assessed with odds ratios and Bayesian random effect 95% credible intervals, with independent extraction by observers. RESULTS: 21 trials were included, focusing on atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, and nebivolol. As expected, in the overall analysis, beta blockers provided credible mortality benefits in comparison with placebo or standard treatment after a median of 12 months (odds ratio 0.69, 0.56 to 0.80). However, no obvious differences were found when comparing the different beta blockers head to head for the risk of death, sudden cardiac death, death due to pump failure, or drug discontinuation. Accordingly, improvements in left ventricular ejection fraction were also similar irrespective of the individual study drug. CONCLUSION: The benefits of beta blockers in patients with heart failure with reduced ejection fraction seem to be mainly due to a class effect, as no statistical evidence from current trials supports the superiority of any single agent over the others.

Chatterjee, S., N. Nerella, et al. (2013). "Angioplasty Alone Versus Angioplasty and Stenting for Subclavian Artery Stenosis-A Systematic Review and Meta-analysis." Am J Ther.

Subclavian artery stenosis has long been treated with great success with bypass surgery. Percutaneous intervention, often used in combination with stent placement, has come into vogue for the past few years as a safe and effective therapeutic modality. This study aimed to compare angioplasty alone with angioplasty followed by stent placement by combining available data. The objective of this study was to perform a review of the available literature to compare the efficacy of percutaneous transluminal angioplasty (PTA) alone with PTA followed by stent placement for proximal subclavian artery stenosis. Successful recanalization was defined as patency at the end of 1 year, and reocclusions and restenoses were noted as events for the purpose of pooling the data. The authors searched the Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, and CINAHL databases for relevant trials/studies comparing PTA and PTA with stenting. Review authors independently assessed the methodological quality of studies (focusing on the adequacy of the randomization process, allocation concealment, blinding, completeness of follow-up, and intention-to-treat analysis) and selected studies for inclusion. All retrospective observational studies were also included in the analysis in the absence of double-blinded randomized trials for increasing sample size. All analyses were done using RevMan 5.0. Odds ratio was calculated using Mantel-Haenszel test with a fixed effect model. All included studies were assessed by all authors for potential sources of bias. Eight studies were included in the analysis having 544 participants. Stenting after PTA was significantly superior to angioplasty alone for treatment of subclavian artery stenosis and maintenance of patency at 1 year, as indicated by absence of events (P = 0.004; 95% confidence interval, odds ratio 2.37 [1.32-4.26]) without significant complication rates for either procedure. There is evidence in favor of stent placement after angioplasty for successful recanalization of stenosed subclavian arteries and long-term maintenance of patency without significant increase in risk for major complications in subjects.

Chatterjee, S., P. Sardar, et al. (2013). "Pharmacologic rate versus rhythm-control strategies in atrial fibrillation: an updated comprehensive review and meta-analysis." Pacing Clin Electrophysiol 36(1): 122-33.

BACKGROUND: In patients with atrial fibrillation (AF), ventricular rate control with medications has been found to be noninferior in preventing clinical events, compared to a strategy converting patients to sinus rhythm and maintaining it with medications. Guidelines have accepted rate control as an acceptable therapeutic option. Most of the prior studies excluded patients without significant left ventricular dysfunction, or permanent AF. METHODS: The authors searched the PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966 to 2011. Trials included were direct head-to-head comparisons of rate- and rhythm-control strategy using pharmacological means. The primary outcome assessed was risk of all-cause mortality. We also assessed other pooled clinical endpoints using a random effects model (Mantel-Haenszel) between rate and rhythm-control strategies. RESULTS: Ten studies (total N = 7,867) met inclusion/exclusion criteria. In-hospital mortality was not different between groups (P = 0.31). The rates of stroke, systemic embolism, worsening heart failure, myocardial infarction, and bleeding were also similar. However, rates of rehospitalization were much lower with a rate-control strategy (P = 0.007). An exploratory analysis in patients younger than 65 years revealed a rhythm-control strategy was superior to rate control in the prevention of all-cause mortality (P = 0.0007). CONCLUSIONS: This systematic review suggests no difference in clinical outcomes with a rate or rhythm-control strategy with AF. However, rehospitalization rates appear to be lower with pharmacological rate control for all ages, while finding support for rhythm control in younger patients.

Chatterjee, S., J. Wetterslev, et al. (2013). "Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis." JAMA Intern Med 173(2): 132-9.

BACKGROUND: The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists. METHODS: A systematic search of studies published between January 1, 1966, and March 31, 2012, was conducted using MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. English-language studies comparing blood transfusion with no blood transfusion or a liberal vs restricted blood transfusion strategy were identified. Two study authors independently reviewed 729 originally identified titles and abstracts and selected 10 for analysis. Study title, follow-up period, blood transfusion strategy, and mortality outcomes were extracted manually from all selected studies, and the quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology checklist. RESULTS: Studies of blood transfusion strategy in anemia associated with myocardial infarction were abstracted, as well as all-cause mortality rates at the longest available follow-up periods for the individual studies. Pooled effect estimates were calculated with random-effects models. Analyses of blood transfusion in myocardial infarction revealed increased all-cause mortality associated with a strategy of blood transfusion vs no blood transfusion during myocardial infarction (18.2% vs 10.2%) (risk ratio, 2.91; 95% CI, 2.46-3.44; P < .001), with a weighted absolute risk increase of 12% and a number needed to harm of 8 (95% CI, 6-17). Multivariate meta-regression revealed that blood transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P = .03). CONCLUSIONS: Blood transfusion or a liberal blood transfusion strategy compared with no blood transfusion or a restricted blood transfusion strategy is associated with higher all-cause mortality rates. A practice of routine or liberal blood transfusion in myocardial infarction should not be encouraged but requires investigation in a large trial with low risk for bias.

Chaudhary, S., A. K. Panda, et al. (2013). "Association of +331G/A PgR polymorphism with susceptibility to female reproductive cancer: evidence from a meta-analysis." PLoS One 8(1): e53308.

The progesterone receptor (PgR), a sex steroid hormone receptor that binds progesterone is critical for normal breast development. The PgR (+331G/A, rs10895068) promoter polymorphism is associated with cancer risk possibly by altering the expression of progesterone receptor B isoform. Previous studies have provided inconsistent results. To validate the association between the PgR +331G/A polymorphism and female reproductive cancer risk (breast, endometrial and ovarian cancer), we performed a meta-analysis of 19 studies (19,978 cases and 24,525 controls) by using the CMA Version 2 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results indicated that the variant allele and genotypes were associated with a mild increase in overall female reproductive cancer risk (A vs. G: OR = 1.063, 95% CI = 1.001-1.129; AA+AG vs. GG: OR = 1.067, 95% CI = 1.002-1.136). The results suggest that the PgR +331G/A polymorphism might be associated with an increased female reproductive cancer risk.

Che, D. H., J. Y. Cao, et al. (2013). "The efficacy and safety of low-molecular-weight heparin use for cancer treatment: A meta-analysis." Eur J Intern Med.

BACKGROUND: Low-molecular-weight heparin (LMWH) has an anti-tumour effect in-vitro and in animal models of malignancy; however, the evidence from clinical trials is controversial. Thus, we performed a meta-analysis from the results of randomised controlled trials (RCTs) to assess LMWH efficacy and safety in cancer patients who had no venous thromboembolism (VTE). METHODS: We searched the MEDLINE, EMBASE and CENTRAL (The Cochrane Central Register of Controlled Trails) databases covering all papers published up until April 2012. Two reviewers (D. H. Che and J. Y. Cao) extracted the data independently. The inclusion criteria used were patients with cancer who had no VTE and were treated with LMWH. The outcomes of interest included the 1-year mortality rate, VTE, bleeding and major bleeding complications. The results were presented as a relative risk (RR), and the STATA 11.0 package was used for comprehensive quantitative analysis. RESULTS: A total of 11 studies with 3835 cases and 3449 controls were included. The meta-analysis showed significant differences in the rates of bleeding with an RR: 1.32 [95% confidence interval (95% CI, 1.08-1.62)] and VTE with an RR: 0.53 (95% CI, 0.42-0.67) in cancer patients when LMWH was compared with placebo or no anticoagulant. There were no significant differences in the 1-year mortality rate with an RR: 0.97 (95% CI, 0.92-1.02) and major bleeding with an RR: 1.22 (95% CI, 0.87-1.71). CONCLUSION: LMWH does not significantly reduce the 1-year mortality rate for cancer patients. Although LMWH can prevent VTE, we should consider the risk-effect ratio (in case of an increased bleeding event) when we use LMWH in the patients with cancer. Thus, further research is still needed to confirm these results.

Chen, C., T. Xu, et al. (2013). "The efficacy of temozolomide for recurrent glioblastoma multiforme." Eur J Neurol 20(2): 223-30.

BACKGROUND AND PURPOSE: The efficacy of temozolomide (TMZ) in recurrent glioblastoma multiforme (GBM) has been evaluated by several clinical trials. A meta-analysis to assess the overall efficacy of TMZ in the treatment of recurrent GBM was carried out by the authors. METHODS: Medline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies were clinical trials of recurrent GBMs assigned to TMZ with data on efficacy including tumor response, progression-free survival (PFS) or overall survival (OS) available. The overall efficacy was calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included trials. RESULTS: A total of 15 phase II clinical trials including 902 recurrent GBMs were analyzed. The overall clinical benefit rate was 50.5% (95% CI: 44.3-56.7%) with significant difference between metronomic and standard schedules of TMZ (61.4% vs. 46.3%, P = 0.037). The overall 6-month PFS (PFS-6) rate was found to be 27.8% (95% CI: 22.7-33.5%) with significant difference between metronomic and standard schedules (33.1% vs. 20.1%, P < 0.001). In addition, significant difference in PFS-6 was detected between high (average daily dose >100 mg/m(2) ) and low (average daily dose </= 100 mg/m(2) ) dose metronomic schedules (RR = 1.57, 95% CI: 1.17-2.09, P = 0.002). The overall 6-month OS (OS-6) and 12-month OS (OS-12) rates were 65.0% (95% CI: 57.4-71.9%) and 36.4% (95% CI: 26.9-47.1%) separately. There was no significant difference in OS-6 between metronomic and standard schedules (P = 0.266); however, a trend was noted favoring the metronomic schedule for OS-12 (P = 0.089). CONCLUSIONS: Temozolomide is effective for recurrent GBMs, and its efficacy may be increased with metronomic schedule and high average daily dose (>100 mg/m(2) ).

Chen, C. Y., L. Y. Lu, et al. (2013). "Shengmai injection, a traditional chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis." Evid Based Complement Alternat Med 2013: 703815.

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate ( < 0.01), decreasing the incidence of IDH episode ( < 0.01), decreasing the frequency of nursing interventions ( < 0.01), and increasing diastolic blood pressure ( < 0.01). There was no statistical significance in the improvement of mean arterial pressure ( = 0.22) and systolic blood pressure ( = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

Chen, D. T., X. Jiang, et al. (2013). "Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder." Mol Psychiatry 18(2): 195-205.

Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of approximately 750,000 high-quality genetic markers on a combined sample of approximately 14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of approximately 17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 x 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the approximately 105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.

Chen, G. C., D. B. Lv, et al. (2013). "Dietary fiber intake and stroke risk: a meta-analysis of prospective cohort studies." Eur J Clin Nutr 67(1): 96-100.

BACKGROUND/OBJECTIVES: Epidemiological studies have suggested that dietary fiber intake may be associated with a decreased risk of stroke, but the findings have been inconsistent. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on PubMed database through July 2012 to identify prospective studies of dietary fiber intake in relation to risk of stroke. We also comprehensively reviewed the reference lists of the retrieved articles to identify additional studies. We used a random-effects model to compute the summary risk estimates. RESULTS: Six prospective cohort studies containing a total of 314 864 subjects and 8920 stroke cases were included. The summary relative risk (RR) of stroke for the highest vs lowest category of dietary fiber intake was 0.87 (95% confidence interval (CI), 0.77-0.99). The corresponding RR in the subgroup analyses for men and women was 0.95 (95% CI, 0.83-1.08) and 0.80 (95% CI, 0.66-0.96), respectively; and for ischemic stroke and hemorrhagic stroke was 0.83(95% CI, 0.72-0.96) and 0.86 (95% CI, 0.70-1.06), respectively. Meta-regression indicated no significant difference between gender (P-interaction=0.18), or stroke subtypes (P-interaction =0.85). The dose-response analysis suggested a 12% (RR=0.88; 95% CI, 0.79-0.97) reduction in risk of stroke for each 10 g per day increment in dietary fiber intake. Moderate heterogeneity emerged in some of analyses, but disappeared after removing one study substantially contributing to the heterogeneity. Little evidence of publication bias was detected. CONCLUSION: Findings of this meta-analysis indicate a significant inverse dose-response relationship between dietary fiber intake and risk of stroke.

Chen, G. C., D. B. Lv, et al. (2013). "Red and processed meat consumption and risk of stroke: a meta-analysis of prospective cohort studies." Eur J Clin Nutr 67(1): 91-5.

BACKGROUND/OBJECTIVES: Epidemiological evidence is suggestive, but inconclusive, for an association between consumption of red and processed meat and risk of stroke. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on PubMed database through June 2012 to identify prospective cohort studies of red and processed meat intake in relation to risk of stroke. Reference lists of the retrieved articles were also reviewed. Both fixed-effects and random-effects model were assumed to compute the summary risk estimates. RESULTS: Five large independent prospective cohort studies were identified. These studies contained a total of 2 39 251 subjects and 9593 stroke events. Comparing the highest category of consumption with lowest category, the pooled relative risks (RRs) of total stroke were 1.15 (95% confidence interval (CI), 1.05-1.25) for total meat (red and processed meat combined) (n=4), 1.09 (95% CI, 1.01-1.18) for red meat (n=5) and 1.14 (95% CI, 1.05-1.25) for processed meat (n=5); the corresponding RRs of ischemic stroke (highest vs lowest quintile) were 1.15 (95% CI, 1.04-1.28), 1.13(95% CI, 1.01-1.25) and 1.19 (95% CI, 1.08-1.31). Consumption of red and/or processed meat was not associated with hemorrhagic stroke. In the dose-response analysis, the risk of stroke increased significantly by 10% and 13% for each 100 g per day increment in total and red meat consumption, respectively, and by 11% for each 50 g per day increment in processed meat consumption. CONCLUSION: Findings from this meta-analysis indicate that consumption of red and/or processed meat increase risk of stroke, in particular, ischemic stroke.

Chen, G. J. and M. S. Yang (2013). "The Effects of Calcium Channel Blockers in the Prevention of Stroke in Adults with Hypertension: A Meta-Analysis of Data from 273,543 Participants in 31 Randomized Controlled Trials." PLoS One 8(3): e57854.

Hypertension is a major risk factor for the development of stroke. It is well known that lowering blood pressure decreases the risk of stroke in people with moderate to severe hypertension. However, the specific effects of calcium channel blockers (CCBs) against stroke in patients with hypertension as compared to no treatment and other antihypertensive drug classes are not known. This systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated CCBs effect on stroke in patients with hypertension in studies of CCBs versus placebo, angiotensin-converting-enzyme inhibitors (ACEIs), beta-adrenergic blockers, and diuretics. The PUBMED, MEDLINE, EMBASE, OVID, CNKI, MEDCH, and WANFANG databases were searched for trials published in English or Chinese during the period January 1, 1996 to July 31, 2012. A total of 177 reports were collected, among them 31 RCTs with 273,543 participants (including 130,466 experimental subjects and 143,077 controls) met the inclusion criteria. In these trials a total of 9,550 stroke events (4,145 in experimental group and 5,405 in control group) were reported. CCBs significantly decreased the incidence of stroke compared with placebo (OR = 0.68, 95% CI 0.61-0.75, p<1x10-5), beta-adrenergic blockers combined with diuretics (OR = 0.89, 95% CI 0.83-0.95, p = 7x10-5) and beta-adrenergic blockers (OR = 0.79, 95% CI 0.72-0.87, p<1x10-5), statistically significant difference was not found between CCBs and ACEIs (OR = 0.92, 95% CI 0.8-1.02, p = 0.12) or diuretics (OR = 0.95, 95% CI 0.84-1.07, p = 0.39). In a pooled analysis of data of 31 RCTs measuring the effect of CCBs on stroke, CCBs reduced stroke more than placebo and beta-adrenergic blockers, but were not different than ACEIs and diuretics. More head to head RCTs are warranted.

Chen, J., S. Y. Chen, et al. (2013). "Pharmacodynamic Impacts of Proton Pump Inhibitors on the Efficacy of Clopidogrel In Vivo-A Systematic Review." Clin Cardiol.

BACKGROUND: There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data. HYPOTHESIS: PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events. METHODS: PubMed, the Cochrane Library, Embase, Web of Science, and China Biology Medicine Disc were searched. Randomized controlled trials that compared pharmacodynamic impacts of a PPI on the efficacy of clopidogrel in vivo were included. Two independent reviewers evaluated study quality and extracted data for meta-analysis. RESULTS: We identified 8 eligible studies. Compared to clopidogrel treatment alone, patients who received both a PPI and clopidogrel had less of a decrease in the platelet reactivity index (weighted mean difference [WMD]: 8.18; 95% confidence interval [CI]: 6.81-9.56; P < 0.00001), less adenosine 5'-diphosphate-induced platelet aggregation inhibition (WMD: 7.28; 95% CI: 2.44-12.11; P = 0.003), higher P2Y12 reaction units (WMD: 40.58; 95% CI: 19.31-61.86; P = 0.0002), and higher risks of clopidogrel resistance (odds ratio [OR]: 2.49; 95% CI: 1.49-4.14; P = 0.0005). There were no significant differences, however, for the incidences of major adverse cardiovascular events between the 2 groups (OR: 1.07; 95% CI: 0.44-2.59; P = 0.88), and treatment with a PPI and clopidogrel significantly reduced the risk of adverse gastrointestinal events (OR: 0.16; 95% CI: 0.04-0.62; P = 0.008). CONCLUSIONS: Concomitant use of a PPI with clopidogrel attenuated the antiplatelet effect of clopidogrel, but may be clinically unimportant because there were no clinical differences in the risk for major adverse cardiovascular events. Additional Supporting Information may be found in the online version of this article. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Chen, J., Y. Ye, et al. (2013). "Association between KRAS codon 13 mutations and clinical response to anti-EGFR treatment in patients with metastatic colorectal cancer: results from a meta-analysis." Cancer Chemother Pharmacol 71(1): 265-72.

PURPOSE: To comparatively evaluate whether metastatic colorectal cancer (mCRC) patients with KRAS codon 13 mutations (codon 13 muts) can benefit from anti-EGFR treatment. METHODS: We performed a meta-analysis of relevant studies. Systematic searches of the PubMed, Embase, and Cochrane databases, as well as ASCO conference papers up to July 30, 2012, were retrieved, and the authors of included studies were contacted to obtain more individual data. Fixed effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end points were the overall response rate (ORR). Secondary end points were progress-free survival (PFS) and overall survival (OS). RESULTS: A total of 7 studies were included in the final meta-analysis, consisting of 2,802 mCRC patients, 1,679 of whom were treated with anti-EGFR monoclonal antibodies. The ORR of mCRC patients with codon 13 mutation was 25.2 % (29/115), compared to 17.6% (98/558) for other KRAS mutations (other mut) and 42.6% (429/1,006) for KRAS WT patients. The overall pooled RR for ORRs of codon 13 mut versus other mut was 1.52 (95% CI 1.10-2.09, P = 0.003), whereas the pooled RR for codon 13 mut versus WT was 0.61 (95% CI 0.45-0.83, P = 0.002). The pooled progression-free survival (PFS) times were 6.4 months for codon 13 mut, 4.1 months for other mut, and 6.6 months for WT, whereas the pooled OS durations were 14.6, 11.8, and 17.3 months, respectively. Subgroup analysis was conducted on the basis of the line of treatment, anti-EGFR drug, study design, and detection method, respectively. The results implicated that KRAS codon 13 mut patients gain more benefit from Cetuximab in further line treatment. CONCLUSIONS: Metastatic colorectal cancer patients with KRAS codon 13 mutations demonstrate a greater clinical response to anti-EGFR treatment than patients with other KRAS mutations.

Chen, K. C., Y. K. Yang, et al. (2013). "Striatal Dopamine Transporter Availability in Drug-Naive Patients With Schizophrenia: A Case-Control SPECT Study With [99mTc]-TRODAT-1 and a Meta-Analysis." Schizophr Bull 39(2): 378-86.

Central dopaminergic hyperactivity has been one of the main hypotheses of the pathophysiology of schizophrenia since the 1970s. Excess dopamine (DA) neurotransmission in the striatum is hypothesized to alter the processing of information and result in psychotic symptoms in schizophrenia. Single photon emission computerized tomography (SPECT) provides in vivo indices of DA neurotransmission. Our study aimed to compare dopamine transporter (DAT) availability between drug-naive patients with schizophrenia and controls using SPECT. DAT availability through [(99m)Tc]-TRODAT-1 SPECT was compared between 47 drug-naive patients with recent-onset schizophrenia and 112 healthy controls. We also conducted a random-effects meta-analysis of the available literature synthesizing the results of 6 comparable published articles as well as our current data. The mean specific striatal binding showed a statistical trend for a reduction among the patients compared with controls (estimated difference = 0.071; 95% CI -0.01, 0.15; P = .08). There was an effect of gender, whereby females had a higher ratio of specific striatal binding than males. Age was negatively correlated with the ratio of specific striatal binding, both in patients and controls. The meta-analysis provided a pooled standardized effect size (Cohen's d) of -0.07 (95% CI -0.31, 0.18; P = .60) for the patient vs control comparison in TRODAT binding, with no evidence of heterogeneity between studies or publication bias. Our findings suggest that striatal DAT levels are not altered in the early stages of schizophrenia before medication is introduced. We identified gender differences and aging effects that could have significance for future studies.

Chen, L., J. Y. Tong, et al. (2013). "Long-term effects of bone marrow-derived cells transplantation in patients with acute myocardial infarction: a meta-analysis." Chin Med J (Engl) 126(2): 353-60.

BACKGROUND: The long-term effects of bone marrow-derived cells (BMC) transplantation in patients with acute myocardial infarction (AMI) have not been established. The present meta-analysis of randomized controlled trials with follow-up >/= 2 years was performed to investigate the long-term effects of BMC therapy in patients after AMI. METHODS: Specific terms were used to conduct a systematic literature search of MEDLINE, EMBASE, the Cochrane Library and the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Disk database from their inception to March 2012. A standardized protocol was used to extract information, and random effect model was used to analyze all data except major adverse events. RESULTS: Five trials comprising 510 patients were included. Compared with controls, BMC therapy significantly improved left ventricular ejection fraction (LVEF) (4.18%, 95%CI: 2.02% to 6.35%, P = 0.0002), while mildly but not significantly reduced left ventricular end-systolic volume (-4.47 ml, 95%CI: -10.92 to 1.99, P = 0.17) and left ventricular end-diastolic volume (-2.29 ml, 95%CI: -9.96 to 5.39, P = 0.56). Subgroup analysis revealed that significant improvement of LVEF induced by BMC therapy could be observed in patients with baseline LVEF </= 42%, but disappeared in those with baseline LVEF > 42%. There were trends in favor of BMC therapy for most major clinical adverse events, though most differences were not significant. CONCLUSIONS: Intracoronary BMC infusion in patients with AMI seems to be safe and may further improve LVEF on top of standard therapy; especially the beneficial effects could last for long term. The findings need to be validated in the future.

Chen, M., M. Zang, et al. (2013). "A powerful Bayesian meta-analysis method to integrate multiple gene set enrichment studies." Bioinformatics.

MOTIVATION: Much research effort has been devoted to the identification of enriched gene sets for microarray experiments. However, identified gene sets are often found to be inconsistent among independent studies. This is probably owing to the noisy data of microarray experiments coupled with small sample sizes of individual studies. Therefore, combining information from multiple studies is likely to improve the detection of truly enriched gene classes. As more and more data become available, it calls for statistical methods to integrate information from multiple studies, also known as meta-analysis, to improve the power of identifying enriched gene sets. RESULTS: We propose a Bayesian model that provides a coherent framework for joint modeling of both gene set information and gene expression data from multiple studies, to improve the detection of enriched gene sets by leveraging information from different sources available. One distinct feature of our method is that it directly models the gene expression data, instead of using summary statistics, when synthesizing studies. Besides, the proposed model is flexible and offers an appropriate treatment of between-study heterogeneities that frequently arise in the meta-analysis of microarray experiments. We show that under our Bayesian model, the full posterior conditionals all have known distributions, which greatly facilitates the MCMC computation. Simulation results show that the proposed method can improve the power of gene set enrichment meta-analysis, as opposed to existing methods developed by Shen and Tseng (2010, Bioinformatics, 26, 1316-1323), and it is not sensitive to mild or moderate deviations from the distributional assumption for gene expression data. We illustrate the proposed method through an application of combining eight lung cancer datasets for gene set enrichment analysis, which demonstrates the usefulness of the method. AVAILABILITY: CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chen, N., M. Yang, et al. (2013). "Cerebrolysin for vascular dementia." Cochrane Database Syst Rev 1: CD008900.

BACKGROUND: Vascular dementia is a common disorder without definitive treatments. Cerebrolysin seems to be a promising intervention based on its potential neurotrophic and pro-cognitive effects, but studies of its efficacy have yielded inconsistent results. OBJECTIVES: To assess the efficacy and safety of Cerebrolysin for vascular dementia. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 4 November 2012 using the terms: Cerebrolysin, Cere, FPF1070, FPF-1070. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. SELECTION CRITERIA: All randomized controlled trials of Cerebrolysin for treating vascular dementia without language restriction. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials and evaluated the methodological quality, then extracted and analysed data from the included trials. MAIN RESULTS: Six randomized controlled trials with a total of 597 participants were eligible. The meta-analyses revealed a beneficial effect of Cerebrolysin on general cognitive function measured by mini-mental state examination (MMSE) (weighted mean difference (WMD) 1.10; 95% confidence interval (CI) 0.37 to 1.82) or Alzheimer's Disease Assessment Scale Cognitive Subpart, extended version (ADAS-cog+) (WMD -4.01; 95% CI -5.36 to -2.66). It also improved patients' global clinical function evaluated by the response rates (relative risk (RR) 2.71, 95% CI 1.83 to 4.00). Only non-serious adverse events were observed in the included trials, and there was no significant difference in occurrence of non-serious side effects between groups (RR 0.97, 95% CI 0.49 to 1.94). AUTHORS' CONCLUSIONS: Cerebrolysin may have positive effects on cognitive function and global function in elderly patients with vascular dementia of mild to moderate severity, but there is still insufficient evidence to recommend Cerebrolysin as a routine treatment for vascular dementia due to the limited number of included trials, wide variety of treatment durations and short-term follow-up in most of the trials.

Chen, P., M. Li, et al. (2013). "Higher Blood 25(OH)D Level May Reduce the Breast Cancer Risk: Evidence from a Chinese Population Based Case-Control Study and Meta-Analysis of the Observational Studies." PLoS One 8(1): e49312.

Experimental data suggest a protective effect of vitamin D on breast cancer; however, epidemiologic results remain inclusive. With a Chinese population-based case-control study and meta-analysis of the observational studies, we here systematically evaluated the association of blood 25(OH)D level and breast cancer risk. With 593 breast cancer cases and 580 cancer-free controls from Shanghai, China, we found that 80% of the normal women had severe vitamin D deficiency (less than 20 ng/mL) and 15.2% had mild deficiency (20 to 30 ng/mL) and only 4.8% of women had sufficient vitamin D level (>30 ng/mL) while the proportion was 96.1%, 3.2% and 0.7% respectively for the breast cancer patients. Compared to those with the lowest quartile of plasma 25(OH)D level, women with highest quartile 25(OH)D level showed a significant decreased breast cancer risk (Q4 vs.Q1: OR = 0.10, 95% CI = 0.06-0.15) and every 1 ng/ml increment of plasma 25(OH)D level led to a 16% lower odds of breast cancer (OR = 0.84, 95% CI = 0.81-0.87; P<0.001). From the meta-analysis of the observational studies, we found that women with highest quantile of blood 25(OH)D level was associated with a significantly reduced breast cancer risk compared to those with lowest quantile of blood 25(OH)D level for the 11 nested case-control and retrospective studies (pooled OR = 0.86, 95% CI = 0.75-1.00) and 10 case-control studies (7 population based, OR = 0.35, 95% CI = 0.24-0.52; 3 hospital based, OR = 0.08, 95% CI = 0.02-0.33). These results suggest that vitamin D may have a chemo-preventive effect against breast cancer.

Chen, P., P. Zou, et al. (2013). "The TERT MNS16A polymorphism contributes to cancer susceptibility: Meta-analysis of the current studies." Gene.

The MNS16A polymorphism in the telomerase reverse transcriptase (TERT) gene has been implicated in cancer risk in multiple populations and various types of cancers; however, the results of previous studies exploring this association were inconclusive. To more precisely evaluate the relationship between the TERT MNS16A polymorphism and cancer risk, we performed a meta-analysis based on 8 studies described in 7 articles comprising 7864 controls and 4355 cases. The summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to assess the strength of the association in a fixed-effects model or a random-effects model where appropriate. Heterogeneity among articles and their publication bias were also tested. Overall, the pooled results indicated that the MNS16A polymorphism was significantly associated with increased cancer risk in the homozygote comparison model (SS vs. LL: OR=1.280, 95% CI 1.060-1.547) and the recessive model (SS vs. LL+SL: OR=1.201, 95% CI 1.004-1.436). In the stratified analyses, a statistically significant association was observed among Caucasians and in population-based studies. We also performed the analyses by cancer type, and a significantly increased risk of glioma was found in four genetic models. Our results suggest that the TERT MNS16A polymorphism most likely contributes to an increased risk of cancer. Moreover, the same relationship was found when the studies were stratified by cancer type, ethnicity and source of controls.

Chen, S., Y. Dong, et al. (2013). "Intravenous immunoglobulin plus corticosteroid to prevent coronary artery abnormalities in Kawasaki disease: a meta-analysis." Heart 99(2): 76-82.

OBJECTIVE: To summarise clinical trials that compared the incidence of coronary abnormality between intravenous immune globulin (IVIG) plus corticosteroid therapy and IVIG therapy alone, and to determine the overall efficacy and safety of IVIG plus corticosteroid therapy for the initial treatment of Kawasaki disease. BACKGROUND: Although use of IVIG as initial therapy has been established in Kawasaki disease, the role of corticosteroids therapy is controversial. METHODS: Medline, The Cochrane Library, The Clinical Trials, and Embase Database were searched for published clinical studies up to 31 March 2012. Studies that compare the efficacy of IVIG plus corticosteroid with that of IVIG in treating Kawasaki disease were included. The coronary outcome and adverse events were analysed by meta-analysis. RESULTS: 9 clinical studies with a total of 1011 patients were identified. Meta-analysis of the 9 studies showed that IVIG plus corticosteroid therapy significantly reduced the risk of coronary abnormality (OR: 0.3; 95% CI 0.20 to 0.46). Similar results were observed in subgroup analyses of randomised controlled studies (OR: 0.3; 95% CI 0.18 to 0.5), studies focused on patients with a high risk of IVIG resistance (OR: 0.2; 95% CI 0.1 to 0.36) and studies with blinded-endpoint manner (OR: 0.32; 95% CI 0.19 to 0.55). There was no significant difference in the incidence of severe adverse events between the IVIG plus corticosteroid group, and the IVIG group (OR: 1.24; 95% CI 0.33 to 4.67). CONCLUSIONS: Combination of corticosteroid with the conventional regimen of IVIG as an initial treatment strategy could reduce the risk of coronary abnormality.

Chen, S., Z. Ling, et al. (2013). "The efficacy and safety of cardiac resynchronization therapy combined with implantable cardioverter defibrillator for heart failure: a meta-analysis of 5674 patients." Europace.

AIMS: The purpose of this study was to evaluate the efficacy and safety of cardiac resynchronization plus implantable cardioverter defibrillator (CRT-D) therapy and implantable cardioverter defibrillator (ICD) therapy in treating heart failure by systematically reviewing randomized controlled trials.METHODS AND RESULTS: Databases of Medline, Embase, and Cochrane Library were searched for published studies up to 31 May 2012. and US Food and Drug Administration websites were searched as well. Only randomized controlled trials comparing the efficacy of CRT-D therapy with ICD therapy were enrolled in meta-analysis. Eight randomized controlled trials characterizing 5674 patients were finally included. Meta-analysis found that CRT-D therapy was associated with significant improvement in clinical conditions [odds ratio (OR): 1.66; 95% confidence interval (CI):1.33-2.07] and a reduction in hospitalization (OR: 0.7; 95% CI: 0.6-0.81) and all-cause mortality (OR: 0.8; 95% CI: 0.67-0.95). Although advantages of CRT-D therapy over ICD therapy were obvious, the peri-implantation adverse events of CRT-D therapy remained to be concerns.CONCLUSION: Compared with ICD therapy, patients receiving CRT-D therapy have favourable outcomes regarding improvement in clinical conditions, hospitalization rate, and overall survival, but at a significantly higher risk of peri-implantation adverse events. Future studies are warranted to optimize the clinical application of CRT-D.

Chen, S., X. Song, et al. (2013). "CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis." PLoS One 8(2): e56380.

OBJECTIVE: CD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis. METHODS: A comprehensive literature search for relevant studies published up to December 2012 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which CD133 antigen was detected in situ localisation by immunohistochemical staining were included. This meta-analysis was done using RevMan 4.2 software. RESULTS: We found that a total of 15 studies involving 810 CD133-high and 1487 CD133-low patients met the inclusion criteria for the analysis of 5-year overall survival (OS) rate. In a random-effects model, the results showed that CD133-high expression in colorectal cancer was an independent prognostic marker correlating with both OS rate (RR = 0.67, 95%CI 0.54-0.82, P<0.01) and disease free survival (DFS) rate (RR = 0.71, 95%CI 0.52-0.96, P = 0.03). CD133-high expression was also associated with more T3,4 tumor invasion, N positive and vascular invasion cases, corresponding to a risk difference of 1.12 (95%CI 1.01-1.23, P = 0.03), 1.31 (95%CI 1.06-1.63, P = 0.01) and 1.24 (95%CI 1.08-1.41, P<0.01), respectively. However, when types of histology, lymphatic invasion and distant metastasis were considered, CD133 overexpression was not significantly related with these clinicopathological parameters. CONCLUSION: Our meta-analysis results suggest that CD133 is an efficient prognostic factor in CRC. Higher CD133 expression is significantly associated with poorer clinical outcome and some clinicopathological factors such as T category, N category and vascular invasion in CRC patients.

Chen, T., H. Wang, et al. (2013). "POSSUM and P-POSSUM as Predictors of Postoperative Morbidity and Mortality in Patients Undergoing Hepato-biliary-pancreatic Surgery: A Meta-analysis." Ann Surg Oncol.

BACKGROUND: Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) models are used extensively to predict postoperative morbidity and mortality in general surgery. The aim was to undertake the first meta-analysis of the predictive value of these models in patients undergoing hepato-biliary-pancreatic surgery. METHODS: Eligible articles were identified by searches of electronic databases from 1991 to 2012. All data were specific to hepato-biliary-pancreatic surgery. Predictive value of morbidity and mortality were assessed by calculating weighted observed to expected (O/E) ratios. Subanalysis was also performed. RESULTS: Sixteen studies were included in final review. The morbidity analysis included nine studies on POSSUM with a weighted O/E ratio of 0.78 [95 % confidence interval (CI) 0.68-0.88]. The mortality analysis included seven studies on POSSUM and nine studies on P-POSSUM (Portsmouth predictor equation for mortality). Weighted O/E ratios for mortality were 0.35 (95 % CI 0.17-0.54) for POSSUM and 0.95 (95 % CI 0.65-1.25) for P-POSSUM. POSSUM had more accuracy to predict morbidity after pancreatic surgery (O/E ratio 0.82; 95 % CI 0.72-0.92) than after hepatobiliary surgery (O/E ratio 0.66; 95 % CI 0.57-0.74), in large sample size studies (O/E ratio 0.90; 95 % CI 0.85-0.96) than in small sample size studies (O/E ratio 0.69; 95 % CI 0.59-0.79). CONCLUSIONS: POSSUM overpredicted postoperative morbidity after hepato-biliary-pancreatic surgery. Predictive value of POSSUM to morbidity was affected by the type of surgery and the sample size of studies. Compared with POSSUM, P-POSSUM was more accurate for predicting postoperative mortality. Modifications to POSSUM and P-POSSUM are needed for audit in hepato-biliary-pancreatic surgery.

Chen, W., H. Wang, et al. (2013). "Istradefylline, an adenosine A(2)A receptor antagonist, for patients with Parkinson's Disease: a meta-analysis." J Neurol Sci 324(1-2): 21-8.

OBJECTIVES: To assess the efficacy and safety of istradefylline as an adjunct to levodopa in patients with Parkinson's Disease (PD). METHODS: In this study, we searched the Cochrane Library, MEDLINE, Embase, China Academic Journal Full-text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Scientific Journals Database (VIP), and Wanfang Database. The quality of included studies was strictly evaluated. Data analyses were performed by the Cochrane Collaboration's RevMan5.0 software. RESULTS: Five randomized controlled trials (RCTs) were included. The result showed a significant reduction of the awake time per day spent in the OFF state and improvement of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III in the ON state when receiving istradefylline compared with patients receiving placebo. There was no significant difference between the istradefylline 20mg and the istradefylline 40 mg groups in the UPDRS Part III in the ON state (WMD=1.27, 95% CI [-0.40, 2.95]). The results showed significant differences in dyskinesia (RR=1.63, 95% CI [1.16, 2.29]) compared to istradefylline 40 mg with placebo. There was no significant statistical difference with regard to other adverse events. CONCLUSIONS: The present study showed that istradefylline is safe and effective as an adjunct to levodopa in patients with PD. Future large-scale, higher-quality, long-treatment, and placebo-controlled trials are needed.

Chen, W. K. and C. H. Miao (2013). "The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies." PLoS One 8(2): e56540.

Animal models have shown that regional anesthesia (combined with or without general anesthesia) would attenuate the surgical stress response by preserving immune function and result in better long-term outcome. In order to test the hypothesis that cancer patients who had surgery with epidural anesthesia (EA) would have better outcome (either overall survival [OS] or recurrence-free survival [RFS]) than those who were general anesthesia (GA), we performed this meta-analysis. By searching relevant literature, a total of 14 studies containing 18 sub-studies (seven in OS analysis and eleven in RFS analysis) were identified and meta-analyzed. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the strength of association. For OS, the random-effects model was used to analyze the data and demonstrated an OS benefit in favor of EA compared with GA alone (HR = 0.84, 95% CI 0.74-0.96, P = 0.013). The influence analysis showed the robustness of the results. Specifically, a significantly positive association between EA and improved OS was observed in colorectal cancer (HR = 0.65, 95% CI 0.43-0.99, P = 0.045). For RFS, the random-effects model was used to analyze the data and no significant relationship between RFS benefit and EA (HR = 0.88, 95% CI 0.64-1.22, P = 0.457) was detected. In conclusion, our meta-analysis suggests that epidural anesthesia and/or analgesia might be associated with improved overall survival in patients with operable cancer undergoing surgery (especially in colorectal cancer), but it does not support an association between epidural anesthesia and cancer control. Prospective studies are needed to determine whether the association between epidural use and survival is causative.

Chen, X., L. Liu, et al. (2013). "Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: A meta-analysis." Clin Biochem.

OBJECTIVES: Results from the published studies on the association of ADRA2A (adrenoceptor alpha 2A) variants with type 2 diabetes (T2D) are conflicting and call for further assessment. The aim of this meta-analysis was to quantitatively summarize the effects of the two recently reported ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 on T2D risk. DESIGN AND METHODS: We searched all the publications about the association between the ADRA2A SNPs and T2D from PubMed and ISI database updated on September 2012. Meta-analysis of the overall odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by using the software STATA 11.0. RESULTS: Twelve studies with 40,828 subjects from seven eligible papers were included in the meta-analysis. Overall, the present meta-analysis failed to support a positive association between ADRA2A SNPs (rs553668 and rs10885122) and susceptibility to T2D (OR=1.05, p=0.17, 95% CI: 0.98, 1.12; and OR=1.06, p=0.11, 95% CI: 0.99, 1.13; respectively). However, in the subgroup analysis by ethnicity, the significant association between rs553668 and the risk of T2D was obtained in Europeans under the recessive genetic model (OR=1.36, p=0.02, 95% CI: 1.05, 1.76). CONCLUSIONS: This meta-analysis suggested that the AA genotype of rs553668 in ADRA2A might be a genetic risk factor that increases T2D susceptibility in Europeans. However, rs10885122 was unlikely substantially contribute to T2D susceptibility.

Chen, X., N. Zhang, et al. (2013). "Evaluation of left ventricular diastolic function using tissue Doppler echocardiography and conventional doppler echocardiography in patients with subclinical hypothyroidism aged <60 years: a meta-analysis." J Cardiol 61(1): 8-15.

Studies have suggested that subclinical hypothyroidism (SCH) may have detrimental effects on left ventricular (LV) diastolic function. Whether SCH is a risk factor for LV diastolic dysfunction is controversial. Databases (MEDLINE, PubMed, EMBASE) were searched for cross-sectional studies evaluating LV diastolic function in SCH patients aged <60 years using tissue Doppler echocardiography (TDE) and conventional two-dimensional Doppler echocardiography (2D-DECG) published in the past 12 years. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using fixed or random-effects models. We summarized the results of 14 cross-sectional studies with 675 participants. SCH patients had a significantly lower LV mitral annular E(a) peak velocity (WMD=-1.71 cm/s; 95%CI: -3.02 to -0.40; p<0.05), E(a)/A(a) ratio (WMD=-0.22; 95%CI: -0.40 to -0.05; p<0.05), and significantly higher mitral annular A(a) peak velocity (WMD=0.47 cm/s; 95%CI: 0.10-0.85; p<0.05) than euthyroid subjects using TDE. Subgroup analyses showed that statistical significance existed only in E(a) and E(a)/A(a) parameters when data from "women >/= 90%" were used, and in the A(a) parameter when data from "women<90%" were used. No matter which subgroup of females was used, there were significant differences in LV peak transmitral A velocity (WMD=7.64 cm/s; 95%CI: 4.55-10.73; p<0.05), and E/A ratio (WMD=-0.22; 95%CI: -0.31 to -0.21; p<0.05) but no significant difference in peak transmitral E velocity (p>0.05) between SCH patients and euthyroid controls using 2D-DECG. Therefore, for those aged <60 years, SCH patients had significantly worse parameters of LV diastolic function than euthyroid controls.

Chen, X. D., F. Q. He, et al. (2013). "Laparoscopic splenectomy with or without devascularization of the stomach for liver cirrhosis and portal hypertension: a systematic review." ANZ J Surg 83(3): 122-8.

BACKGROUND: Open splenectomy and devascularization are effective treatments for cirrhotic patients with severe thrombocytopenia and variceal bleeding. However, it remains controversial whether laparoscopic splenectomy (LS) and devascularization (LSD) can be indicated and beneficial in these patients. OBJECTIVES: A systematic review of the efficacy and safety of LS and LSD for patients with liver cirrhosis and portal hypertension was undertaken to clarify controversy about their utilization in such patients. METHODS: A systematic search strategy was performed to retrieve relevant studies from PubMed and The literature search and data extraction were independently performed by two reviewers. RESULTS: Sixteen articles met the inclusion criteria. The methodology of the identified articles was poor. Six hundred and fifty-one patients, including 478 LS patients and 173 LSD patients, were involved in efficacy and safety evaluations. There was wide variability in the outcome measures between studies. There was only one death in the patients underwent LSD. Reported major complications included post-operative bleeding requiring re-surgery, pancreatic leakage and gastric perforation. Seven studies were identified with comparisons between laparoscopic and open procedures. No meta-analysis was possible because of heterogeneity between studies and lack of randomization. CONCLUSIONS: The publications reviewed revealed LS and LSD to be safe and effective in the setting of liver cirrhosis and portal hypertension. From the comparison articles, laparoscopic procedures appear to be superior to open procedures regarding blood loss, hospital stay, complication rate and liver function impairment. However, it is difficult to draw firm statistical conclusions due to lack of high-quality evidence.

Chen, Y., J. Li, et al. (2013). "APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis." Eur J Hum Genet.

Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is limited. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for PCa detection in body fluids and tissues. Combining search results from PubMed and Embase, 19 studies were included, 5 involving body fluids and 14 involving prostate tissue, with 2344 subjects. In body fluid subgroups, the pooled sensitivity and specificity was 0.53 (95% confidence interval (CI): 0.28-0.78) and 0.92 (95% CI: 0.86-0.95), respectively. From tissue studies, the results presented as 0.84 (95% CI: 0.70-0.92) and 0.91 (95% CI: 0.77-0.97). To confirm the results, we conducted a further analysis by removing studies which introduced high heterogeneity due to the type of cases and controls. The same degree of sensitivity and specificity was presented in two subgroups (urine: sensitivity 0.46, 95% CI: 0.39-0.53; specificity 0.87, 95% CI: 0.64-0.96; tissue: sensitivity 0.87, 95% CI: 0.72-0.94; specificity 0.89, 95% CI: 0.68-0.97). In addition, analysis of the interaction between APC methylation and PCa showed strong association in the whole data set (odds ratio (OR)=24.91, 95% CI: 12.86-48.24, I(2)=72.5%). Pooling the same two main subgroups (tissue/fluid) gave a pooled OR of 33.54 (95% CI: 14.88-75.59; I(2)=70.7%) and 8.20 (95% CI: 2.84-23.74, I(2)=64.2%), respectively. From this study, the results suggest that APC promoter methylation may be the potential testing for PCa diagnosis and provide a new viewpoint in the treatment of PCa.European Journal of Human Genetics advance online publication, 9 January 2013; doi:10.1038/ejhg.2012.281.

Chen, Y., L. Meng, et al. (2013). "Aliskiren vs. other antihypertensive drugs in the treatment of hypertension: a meta-analysis." Hypertens Res 36(3): 252-61.

To investigate the antihypertensive effects and tolerability of aliskiren in comparison with other antihypertensive drugs and placebo in patients with hypertension, a meta-analysis was performed of studies published between 1950 and 2012. A systematic literature search of MEDLINE and the Cochrane Library was conducted for randomized controlled trials. Weighted mean differences and relative risk with 95% confidence intervals were calculated for continuous and dichotomous data, respectively. In all, 14 studies with 6741 participants were included in the present meta-analysis. Nine studies included trial arms with placebo, four included angiotensin (Ang) AT1 receptor blockers (ARBs), three included Ang-converting enzyme inhibitors (ACEIs), two included calcium channel blockers (CCBs), one included a beta-blocker, and one included hydrochlorothiazide (HCTZ). We found that aliskiren, which lowered blood pressure (BP) effectively in patients with mild-to-moderate hypertension, was similar to HCTZ but inferior to CCBs in BP reduction, response rates and control rates. Furthermore, aliskiren was superior to ACEIs in lowering diastolic BP (DBP), while it had similar effects to ACEIs on systolic BP (SBP) reduction, response rates and control rates. Additionally, the present meta-analysis showed the superiority of atenolol over aliskiren in DBP reduction and BP response but showed that atenolol was inferior in SBP reduction and BP control. No difference was found in the rates of therapeutic response between aliskiren and ARBs, while more patients achieved BP control with aliskiren. Further studies will be needed to determine the antihypertensive effects and tolerability of aliskiren in comparison with other antihypertensive drugs.

Chen, Y., S. A. Nah, et al. (2013). "Transanal endorectal pull-through versus transabdominal approach for Hirschsprung's disease: A systematic review and meta-analysis." J Pediatr Surg 48(3): 642-651.

AIM: Transanal endorectal pull-through (TERPT) has become popular for single-stage treatment of Hirschsprung's disease. The benefits of TERPT over the conventional transabdominal approach (TAB) are still unclear. We performed a comprehensive meta-analysis comparing the clinical outcomes of TERPT and TAB. METHODS: Original articles published from 1998 to 2012 were searched from Medline, Embase, and Cochrane databases. Randomized controlled trials (RCT) and observational clinical studies (OCS) comparing TERPT and TAB were included. Outcomes evaluated included operative time, hospital stay and incidence of postoperative incontinence/soiling, constipation and enterocolitis. Pooled odds ratios (OR) were calculated for dichotomous variables; pooled mean differences (MD) were measured for continuous variables. RESULTS: Of 93 studies, 1 RCT and 11 OCS were included, comprising 444 cases of TERPT and 348 cases of TAB (215 Soave, 94 Duhamel, 24 Swenson, 15 Rehbein procedures). TERPT had shorter operative time (MD=-57.85min; 95% confidence interval [CI], -83.11 to -32.60; P<0.00001) and hospital stay (MD=-7.06days; 95% CI, -10.95 to -3.16; P=0.0004). TERPT had less postoperative incontinence/soiling (OR=0.58; 95% CI 0.37-0.90; P=0.01) and constipation (OR=0.49; 95% CI 0.30-0.81; P=0.005). There was no difference in incidence of postoperative enterocolitis. CONCLUSION: TERPT is superior to TAB in operative time, hospital stay, postoperative incontinence and constipation. However, more randomized controlled trials are necessary to verify the benefit of TERPT for Hirschsprung's disease.

Chen, Y., A. Schieppati, et al. (2013). "Immunosuppression for Membranous Nephropathy: A Systematic Review and Meta-Analysis of 36 Clinical Trials." Clin J Am Soc Nephrol.

BACKGROUND AND OBJECTIVES: The efficacy and safety of immunosuppression for idiopathic membranous nephropathy (IMN) with nephrotic syndrome are still controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cochrane Library, PUBMED, EMBASE, Chinese Database, and Clinical Trial Registries (June 2012) were searched to identify RCTs investigating the effect of immunosuppression on adults with IMN and nephrotic syndrome. RESULTS: This review was an update (36 RCTs, 1762 participants) of the 2004 version (18 RCTs, 1025 participants). Immunosuppression significantly reduced all-cause mortality or ESRD (15 RCTs, 791 participants; risk ratio, 0.58 [95% confidence interval, 0.36-0.95]; P=0.03). However, the result was not consistent when prespecified subgroup analyses were undertaken. Immunosuppression increased complete or partial remission (CR + PR) (16 RCTs, 864 participants; 1.31 [1.01-1.70]; P=0.04) but resulted in more withdrawals or hospitalizations (16 RCTs, 880 participants; 5.35 [2.19-13.02]; P=0.002). Corticosteroids combined with alkylating agents significantly reduced all-cause mortality or ESRD (8 RCTs, 448 participants; 0.44 [0.26-0.75]; P=0.002) and increased CR + PR (7 RCTs, 422 participants; 1.46 [1.13-1.89]; P=0.004) but led to more adverse events (4 RCTs, 303 participants; 4.20 [1.15-15.32]; P=0.03). Cyclophosphamide was safer than chlorambucil (3 RCTs, 147 participants; 0.48 [0.26-0.90]; P=0.02). Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents. Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria. CONCLUSIONS: Alkylating agents plus corticosteroids had long-term and short-term benefits for adult IMN, but resulted in more withdrawals or hospitalizations.

Chen, Y. C., G. H. Dong, et al. (2013). "Gender difference of childhood overweight and obesity in predicting the risk of incident asthma: a systematic review and meta-analysis." Obes Rev 14(3): 222-31.

The aims of our meta-analysis were (i) to quantify the predictability of childhood overweight and obesity on the risk of incident asthma; and (ii) to evaluate the gender difference on this relationship. The selection criteria included prospective cohort paediatric studies which use age- and sex-specific body mass index (BMI) as a measure of childhood overweight and the primary outcome of incident asthma. A total of 1,027 studies were initially identified through online database searches, and finally 6 studies met the inclusion criteria. The combined result of reported relative risk from the 6 included studies revealed that overweight children conferred increased risks of incident asthma as compared with non-overweight children (relative risk, 1.19; 95% confidence interval [CI], 1.03-1.37). The relationship was further elevated for obesity vs. non-obesity (relative risk, 2.02; 95% CI, 1.16-3.50). A dose-responsiveness of elevated BMI on asthma incidence was observed (P for trend, 0.004). Obese boys had a significantly larger effect than obese girls (relative risk, boys: 2.47; 95% CI, 1.57-3.87; girls: 1.25; 95% CI, 0.51-3.03), with significant dose-dependent effect. Proposed mechanisms of gender difference could be through pulmonary mechanics, sleep disordered breathing and leptin. Further research might be needed to better understand the exact mechanism of gender difference on the obesity-asthma relationship.

Chen, Z., M. Fei, et al. (2013). "Association between cytotoxic T lymphocyte antigen-4 polymorphism and type 1 diabetes: A meta-analysis." Gene 516(2): 263-70.

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an important mediators of T-cell activation in autoimmune diseases. The association of polymorphisms of CTLA gene with type 1 diabetes (T1D) has widely been reported; however, the results are inconsistent. To obtain further insight into this topic, we performed a meta-analysis of 52 studies involving a total of 11,017 cases and 14,191 controls for 49A/G (rs231775) polymorphism of the CTLA-4 gene to evaluate the effect of CTLA-4 on genetic susceptibility for T1D. An overall random effects odds ratio of 1.41 (95% CI: 1.31-1.53, p<10(-5)) was found for G allele versus A allele. Significant results were also observed for heterozygous (OR=1.29, 95% CI: 1.16-1.45, p<10(-5)) and homozygous (OR=1.96, 95% CI: 1.66-2.31, p<10(-5)). When stratified by ethnicity, sample size, diagnostic criterion, HWE status, genotyping method, and onset types, significantly increased risks were found for the polymorphism in almost all genetic models. Subgroup analysis and meta-regression was used to identify potential source of heterogeneity. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. This meta-analysis demonstrated that the G allele of rs231775 of CTLA-4 is a risk factor associated with increased T1D susceptibility.

Chen, Z., J. Qian, et al. (2013). "Addition of Cilostazol to Conventional Dual Antiplatelet Therapy Reduces the Risk of Cardiac Events and Restenosis After Drug-Eluting Stent Implantation: A Meta-Analysis." J Clin Pharmacol.

This meta-analysis was performed to compare the risk of cardiac events and restenosis between triple antiplatelet therapy (TAT, addition of cilostazol to aspirin and clopidogrel) and conventional dual antiplatelet therapy (DAT, aspirin and clopidogrel) in drug-eluting stents (DES) implantation patients. We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation. Five clinical trials were involved in the study. TAT was associated with a 36% reduction in major adverse cardiac events (MACE; odds ratio (OR) = 0.64; 95% confidence interval (CI) = 0.51-0.81, P < .01), a 40% reduction (OR = 0.60, 95% CI = 0.44-0.80; P < .01) in target vessel revascularization (TVR), a 44% reduction (OR = 0.56, 95% CI = 0.34-0.91; P = .02) in target lesion revascularization (TLR) and a 47%/44% reduction in in-segment/in-stent restenosis (P < .01) and lower in-segment/in-stent late loss (P < .01). As regards to the safety assessment, there was no significant difference about the risk of stent thrombosis and bleeding between TAT and DAT group, while the risk of gastrointestinal trouble was significantly higher in TAT group (OR = 2.46, 95% CI = 1.25-4.86; P < .01). Addition of cilostazol to DAT reduced the incidence of MACE, TVR, and TLR after DES implantation. TAT also reduced the risk of restenosis and late loss in patients after DES implantation.

Chen, Z., L. Zhu, et al. (2013). "TNF-alpha-308 G>A polymorphism and colorectal cancer risk: a meta-analysis." Int J Colorectal Dis 28(3): 431-2.

Cheng, C., S. F. Cheung, et al. (2013). "Cultural meaning of perceived control: a meta-analysis of locus of control and psychological symptoms across 18 cultural regions." Psychol Bull 139(1): 152-88.

Integrating more than 40 years of studies on locus of control (LOC), this meta-analysis investigated whether (a) the magnitude of the relationship between LOC and psychological symptoms differed among cultures with distinct individualist orientations and (b) depression and anxiety symptoms yielded different patterns of cultural findings with LOC. We included studies that examined global self-ratings of LOC and at least 1 of the criterion variables in nonclinical samples (age range: 18-80 years). Data were analyzed on the basis of 152 independent samples, representing the testing of 33,224 adults across 18 cultural regions. Results revealed moderately strong relationships for external LOC with depression symptoms (k = 123, N = 28,490, r = .30, 95% confidence interval [CI] [.27, .32]) and anxiety symptoms (k = 65, N = 13,208, r = .30, 95% CI [.27, .33]). Individualism explained 20% of unique variance only in the external LOC-anxiety relationship: The link between external LOC and anxiety symptoms was weaker for collectivist societies (k = 8, N = 2,297, r = .20, 95% CI [.13, .28]) compared with individualist societies (k = 54, N = 9,887, r = .32, 95% CI [.29, .34]). Such cultural differences were attributed to the reduced emphasis on agentic goals in more collectivist societies. It is noteworthy that external LOC does not carry the same negative connotations across cultures, and members of collectivist societies may be more ready to endorse such items. Culture has been examined at the country level, and the findings may not be applicable to any particular person in a cultural region. Implications for integrating cultural meaning of perceived control into formulation of theories, research design, and intervention programs are discussed.

Cheng, G. and A. Alavi (2013). "Value of 18F-FDG PET versus iliac biopsy in the initial evaluation of bone marrow infiltration in the case of Hodgkin's disease: a meta-analysis." Nucl Med Commun 34(1): 25-31.

OBJECTIVE: We carried out a meta-analysis to evaluate the performance of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) PET and PET/CT against bone marrow biopsy (BMB) in the initial diagnosis of bone marrow infiltration (BMI) in patients with Hodgkin's disease (HD). MATERIALS AND METHODS: Retrospective and prospective studies with direct comparison of (18)F-FDG PET with BMB in the initial evaluation of BMI in HD were included. Seven eligible studies were included in the meta-analysis comprising a total of 687 patients. RESULTS: Both (18)F-FDG PET and BMB had excellent specificity in detecting BMI. However, (18)F-FDG PET had excellent pooled sensitivity (94.5%; 95% confidence interval: 89.0-97.8%) in detecting BMI in the initial staging of HD patients, whereas the pooled sensitivity of iliac BMB was very poor (39.4%; 95% confidence interval: 30.8-48.4%). The diagnostic odds ratio, a measure of the overall diagnostic power of the test, was much higher for PET (pooled value of 1591) than for iliac BMB (pooled value of 137). CONCLUSION: (18)F-FDG PET significantly outperforms iliac BMB in the detection of BMI in the initial staging of HD patients and therefore should be used as a first-line study. Iliac BMB has low sensitivity and a high rate of false-negative findings. Thus, a negative BMB finding cannot rule out marrow involvement in HD patients on initial staging.

Cheng, H. M., C. Tufanaru, et al. (2013). "Automated blood pressure measurement in atrial fibrillation: a systematic review and meta-analysis." J Hypertens 31(1): 214-5.

Cheng, J. W., S. W. Cheng, et al. (2013). "The prevalence of visual impairment in older adults in mainland China: a systematic review and meta-analysis." Ophthalmic Res 49(1): 1-10.

PURPOSE: This paper presents estimates of the prevalence of blindness and low vision among older adults over 50 years of age in mainland China. METHODS: All primary reports of population-based studies that reported the prevalence or incidence of visual impairment among older populations in mainland China were identified. Twenty-four population-based studies were included in this systematic review. Blindness is defined as visual acuity of less than 3/60, or a corresponding visual-field loss to less than 10 degrees in the better eye with the best possible correction; low vision is defined as visual acuity of less than 6/18, but equal to or better than 3/60 in the better eye with the best possible correction. The pooled prevalence estimates of blindness and low vision were calculated assuming a random-effects model. Relative odds with 95% confidence intervals (95% CIs) were calculated, stratified by methodological and socioeconomic variables. RESULTS: The overall pooled prevalence of blindness was 1.7% (95% CI 1.4-2.1). The results of the meta-regression showed the significance of a predictor variable: geographic region. The blindness rates per 100 older adults in various regions were 1.4 (0.9-2.0) in East China, and 1.4 (1.0-2.0) in Central China and 2.5 (1.9-3.2) in Western China. The overall pooled prevalence of low vision was 4.1% (3.4-5.1) and the independent pooled prevalence rates stratified by geographic region were 3.6% (2.6-5.1) in East China, 3.6% (2.4-5.2) in Central China and 5.2% (3.6-7.4) in Western China. CONCLUSIONS: Blindness or low vision affects approximately 5.8% Chinese adults older than 50 years. The prevalence of visual impairment, and especially blindness, vary greatly by the developmental status of geographic region.

Cheng, W., C. Ma, et al. (2013). "Low- or High-Dose Radioiodine Remnant Ablation for Differentiated Thyroid Carcinoma: A Meta-Analysis." J Clin Endocrinol Metab.

Context:There is uncertainty over the dose of (131)I required for thyroid remnant ablation. Most previous studies have been inadequately powered to establish the best fixed dose of (131)I for effective ablation.Objective:The aim of the study was to assess the effects of low- vs high-dose regimens of radioiodine in thyroid remnant ablation for patients with differentiated thyroid carcinoma.Data Sources:Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS (all until September 2012).Study Selection:Randomized controlled trials that assess the efficacy of low- or high-dose of radioiodine ablation of thyroid remnants were collected.Data Extraction:Two authors performed the data extraction independently.Data Synthesis:Nine randomized controlled trials involving 2569 patients were included. The 1100-MBq vs the 3700-MBq radioiodine showed no statistically significant difference in successful thyroid remnant ablation (risk ratio [RR], 0.91 [0.79 to 1.04]; P = .15), both the 1100 vs the 1850 MBq (RR, 0.95 [0.83 to 1.10]; P = .52) and the 1850 vs the 3700 MBq (RR, 1.00 [0.85 to 1.17]; P = .98) also showed no significant differences (95% confidence intervals were calculated for each estimate). Also, no significant differences existed in quality-of-life scores on the SF-36 between different (131)I-dose groups both on the day of ablation (RR, 0.15 [-0.65 to 0.96], P = .71; I(2) = 29%, P = .24) and 3 months after ablation (RR, -1.1 [-2.37 to 0.17], P = .09; I(2) = 22%, P = .26). A low dose of 1100 MBq radioiodine showed significant benefits in reducing adverse effects (total RR, 0.65 [0.55 to 0.77], P < .1; I(2) = 31%, P =.14) and shorter hospital isolation (RR, 0.4 [0.32 to 0.50]; P < .05).Conclusions:The low dose of 1100 MBq radioiodine activity is sufficient for thyroid remnant ablation as compared to 3700 MBq radioiodine activity with similar quality of life, less common adverse effects, and a shorter hospital stay.

Cheng, Y., J. Lu, et al. (2013). "Gases for establishing pneumoperitoneum during laparoscopic abdominal surgery." Cochrane Database Syst Rev 1: CD009569.

BACKGROUND: Laparoscopic surgery is now widely performed to treat various abdominal diseases. Currently, carbon dioxide is the most frequently used gas for insufflation of the abdominal cavity (pneumoperitoneum). Many other gases have been introduced as alternatives to carbon dioxide for establishing pneumoperitoneum. OBJECTIVES: To assess the safety, benefits, and harms of different gases for establishing pneumoperitoneum in patients undergoing laparoscopic abdominal surgery. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and Chinese Biomedical Literature Database (CBM) until September 2012. SELECTION CRITERIA: We only included randomized controlled trials comparing different gases for establishing pneumoperitoneum in patients undergoing laparoscopic abdominal surgery under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors identified the trials for inclusion, collected the data, and assessed the risk of bias independently. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Carbon dioxide pneumoperitoneum versus nitrous oxide pneumoperitoneum Three trials randomized 196 participants (the majority with low anaesthetic risk) to carbon dioxide pneumoperitoneum (n =96) or nitrous oxide pneumoperitoneum (n =100). All of the trials were of high risk of bias. Two trials (n=143) showed lower pain scores in nitrous oxide pneumoperitoneum at various time points on the first post-operative day. One trial (n=53) showed no difference in the pain scores between the groups. There were no significant differences in cardiopulmonary complications, surgical morbidity, or cardiopulmonary changes between the groups. There were no serious adverse events related to either carbon dioxide or nitrous oxide pneumoperitoneum. Carbon dioxide pneumoperitoneum versus helium pneumoperitoneum Four trials randomized 144 participants (the majority with low anaesthetic risk) to carbon dioxide pneumoperitoneum (n =75) or helium pneumoperitoneum (n =69). All of the trials were of high risk of bias. Fewer cardiopulmonary changes were observed with helium pneumoperitoneum than carbon dioxide pneumoperitoneum. There were no significant differences in cardiopulmonary complications, surgical morbidity, or pain scores. There were three serious adverse events (subcutaneous emphysema) related to helium pneumoperitoneum. Carbon dioxide pneumoperitoneum versus any other gas pneumoperitoneum There were no randomized controlled trials comparing carbon dioxide pneumoperitoneum to any other gas pneumoperitoneum. AUTHORS' CONCLUSIONS: 1. Nitrous oxide pneumoperitoneum during laparoscopic abdominal surgery appears to decrease post-operative pain in patients with low anaesthetic risk.2. Helium pneumoperitoneum decreases the cardiopulmonary changes associated with laparoscopic abdominal surgery. However, this did not translate into any clinical benefit over carbon dioxide pneumoperitoneum in patients with low anaesthetic risk.3. The safety of nitrous oxide and helium pneumoperitoneum has yet to be established. More randomized controlled trials on this topic are needed. Future trials should include more patients with high anaesthetic risk. Furthermore, such trials need to use adequate methods to reduce the risk of bias.

Cheng, Y., N. Lv, et al. (2013). "18FDG-PET in assessing disease activity in Takayasu arteritis: a meta-analysis." Clin Exp Rheumatol.

OBJECTIVES: To assess the diagnosis value of 18FDG-PET in estimating disease activity in Takayasu arteritis. METHODS: A complete search of PubMed, EMBASE and The Cochrane Library was finished to July 25, 2012. Sensitivity and specificity as well as pooled estimates of positive and negative likelihood ratios (PLR and NLR) were calculated by Meta-Disc. We also calculated the area under the sROC curve (AUC) and the Q* index. RESULTS: The meta-analysis was finished with 6 study retrieved from the database search. The pooled sensitivity, and specificity with 95% confidence interval were 70.1% (95% CI, 58.6-80.0) and 77.2% (95% CI, 64.2-87.3). The PLR and NLR were 2.313 (95% CI 1.108-4.829) and 0.341 (95% CI 0.142-0.824). The AUC was 0.805(+/-0.084) and Q* index was 0.7402 (+/-0.0739). CONCLUSIONS: 18FDG-PET had moderate diagnosis value in assessing TA activity. It may add additional value to the current diagnosis methods.

Cheng, Y. F., H. B. Leu, et al. (2013). "Association between panic disorder and risk of atrial fibrillation:a nationwide study." Psychosom Med 75(1): 30-5.

OBJECTIVE: The aim of the present study was to investigate the association between panic disorder (PD) and atrial fibrillation (AF). METHODS: We used a nationwide population-based data set from Taiwan. A total of 3888 patients with PD and without a diagnosis of AF from a sampled cohort data set of 1,000,000 were included in the study group. Ten people without PD and AF were selected for every 1 patient in the study group, matched by propensity score matching according to time of enrollment, age, sex, and comorbidities. We performed log-rank tests to analyze differences in accumulated AF-free survival rates between the two groups. Cox proportional hazard regressions were performed to evaluate the independent factors determining the longitudinal hazard of AF. RESULTS: During a maximal 7-year follow-up, 48 patients from the study group (1.2% of the patients with PD) and 358 from the control group (0.9% of the patients without PD) were newly diagnosed as having AF. Patients with PD had a significantly higher incidence of AF (hazard ratio [HR] = 1.54 [1.14-2.09]; log-rank test, p = .004). After Cox model adjustment for risk factors and comorbidities, PD (HR = 1.73, 95% confidence interval [CI] = 1.26-2.37), age (HR = 1.07, 95% CI = 1.06-1.08), male sex (HR = 1.26, 95% CI = 1.03-1.55), hypertension (HR = 2.00, 95% CI = 1.55-2.56), history of coronary artery disease (HR = 1.45, 95% CI = 1.15-1.82), congestive heart failure (HR = 2.46; 95% CI, 1.84-3.30), and valvular heart disease (HR = 2.83, 95% CI = 1.85-4.42) were independently associated with increased risk of AF. CONCLUSIONS: PD is independently associated with higher incidence of AF to be diagnosed in the future. Larger prospective studies or meta-analysis are suggested to confirm the findings.

Chery, C., A. Hehn, et al. (2013). "Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant." Biochimie.

Several genome-wide association studies (GWAS) have identified a strong association between serum vitamin B12 and fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. Hazra et al. conducted a meta-analysis of three GWAS and found three additional loci in MUT, CUBN and TCN1. Other GWAS conducted in Italy and China confirmed the association for FUT2 gene. Alpha-2-fucosyltransferase (FUT2) catalyzes fucose addition to form H-type antigens in exocrine secretions. FUT2 non-secretor variant produces no secretion of H-type antigens and is associated with high-plasma vitamin B12 levels. This association was explained by the influence of FUT2 on H. pylori, which is a risk factor of gastritis, a main cause of vitamin B12 impaired absorption. However, we recently showed that H. pylori serology had no influence on FUT2 association with vitamin B12, in a large sample population, suggesting the involvement of an alternative mechanism. GIF is another gene associated with plasma levels of vitamin B12 and gastric intrinsic factor (GIF) is a fucosylated protein needed for B12 absorption. Inherited GIF deficiency produces B12 deficiency unrelated with gastritis. We report 2 families with heterozygous GIF mutation, 290T>C, M97T, with decreased binding affinity of GIF for vitamin B12 and one family with heterozygous GIF mutation 435_437delGAA, K145_N146delinsN and no B12 binding activity of mutated GIF. All cases with vitamin B12 deficit carried the FUT2 rs601338 secretor variant. Ulex europeus binding to GIF was influenced by FUT2 genotypes and GIF concentration was lower, in gastric juice from control subjects with the secretor genotype. GIF290C allele was reported in 5 European cases and no Africans among 1282 ambulatory subjects and was associated with low plasma vitamin B12 and anaemia in the single case bearing the FUT2 secretor variant. We concluded that FUT2 secretor variant worsens B12 status in cases with heterozygous GIF mutations by impairing GIF secretion, independently from H. pylori-related gastritis.

Chi, I., M. Jordan-Marsh, et al. (2013). "Tai chi and reduction of depressive symptoms for older adults: a meta-analysis of randomized trials." Geriatr Gerontol Int 13(1): 3-12.

The aim of the present article was to systematically review the effectiveness of tai chi for reducing depressive symptoms among older adults. Electronic databases were searched through January 2011. Reference lists of systematic reviews and identified studies from the search strategy were also screened. Randomized controlled trials of tai chi compared with waiting list controls in older adults with depressive symptoms measured by a self-report depression rating scale were included. Two authors independently identified eligible studies, extracted data and assessed the included studies for risk of bias. Estimates of depressive symptoms reduction used a random effects model, and the I(2) statistic was applied to examine heterogeneity. Four trials with a total of 253 participants met the inclusion criteria. Two studies were assessed as being of high quality; the remaining two studies were rated as moderate quality. All four studies compared tai chi with a waiting list control group. The pooled standard mean difference for these studies was -0.27 (95% CI -0.52 to -0.02, P=0.03). Tai chi appeared to have a significant impact on reducing depressive symptoms compared with the waiting list control groups. Further research is recommended with larger sample sizes, more clarity on trial design and the intervention, longer-term follow up, and concomitant economic evaluations.

Chlebicki, M. P., N. Safdar, et al. (2013). "Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis." Am J Infect Control 41(2): 167-73.

BACKGROUND: Chlorhexidine showering is frequently recommended as an important preoperative measure to prevent surgical site infection (SSI). However, the efficacy of this approach is uncertain. METHODS: A search of electronic databases was undertaken to identify prospective controlled trials evaluating whole-body preoperative bathing with chlorhexidine versus placebo or no bath for prevention of SSI. Summary risk ratios were calculated using a DerSimonian-Laird random effects model and a Mantel-Haenzel dichotomous effects model. RESULTS: Sixteen trials met inclusion criteria with a total of 17,932 patients: 7,952 patients received a chlorhexidine bath, and 9,980 patients were allocated to various comparator groups. Overall, 6.8% of patients developed SSI in the chlorhexidine group compared with 7.2% of patients in the comparator groups. Chlorhexidine bathing did not significantly reduce overall incidence of SSI when compared with soap, placebo, or no shower or bath (relative risk, 0.90; 95% confidence interval: 0.77-1.05, P = .19). CONCLUSIONS: Meta-analysis of available clinical trials suggests no appreciable benefit of preoperative whole-body chlorhexidine bathing for prevention of SSI. However, most studies omitted details of chlorhexidine application. Better designed trials with a specified duration and frequency of exposure to chlorhexidine are needed to determine whether preoperative whole-body chlorhexidine bathing reduces SSI.

Choi, J., Y. Fukuoka, et al. (2013). "The effects of physical activity and physical activity plus diet interventions on body weight in overweight or obese women who are pregnant or in postpartum: A systematic review and meta-analysis of randomized controlled trials." Prev Med.

OBJECTIVE: To review the effectiveness of physical activity (PA) and PA plus diet interventions in managing weight among overweight or obese (OW/OB) pregnant or postpartum women. METHODS: Four databases were searched for randomized controlled studies published between January 2000 and December 2011 that reported weight change outcomes of PA interventions in OW/OB pregnant or postpartum women. PA alone as well as PA plus diet interventions was included. RESULTS: Of 681 abstracts identified, 11 were included (7 trials with pregnant women and 4 trials with postpartum women). Overall, we found that PA interventions were effective for OW/OB pregnant as well as postpartum women. On average, pregnant women in the intervention groups gained 0.91kg less (95% CI: -1.76, -0.06) compared with those in the usual care groups. Postpartum women in the intervention groups significantly lost more body weight (-1.22kg; 95% CI: -1.89, -0.56) than those in the control groups. In the subgroup analyses by PA intervention types, supervised PA plus diet interventions were the most effective. CONCLUSIONS: PA plus diet interventions may require more than advice; supervised PA programs or personalized prescription/goals are needed to prevent excessive weight gain for OW/OB pregnant women and excessive weight retention for OW/OB postpartum women.

Choi, J., L. Joseph, et al. (2013). "Obesity and C-reactive protein in various populations: a systematic review and meta-analysis." Obes Rev 14(3): 232-44.

Obesity has been associated with elevated levels of C-reactive protein (CRP), a marker of inflammation and predictor of cardiovascular risk. The objective of this systematic review and meta-analysis was to estimate the associations between obesity and CRP according to sex, ethnicity and age. MEDLINE and EMBASE databases were searched through October 2011. Data from 51 cross-sectional studies that used body mass index (BMI), waist circumference (WC) or waist-to-hip ratio (WHR) as measure of obesity were independently extracted by two reviewers and aggregated using random-effects models. The Pearson correlation (r) for BMI and ln(CRP) was 0.36 (95% confidence interval [CI], 0.30-0.42) in adults and 0.37 (CI, 0.31-0.43) in children. In adults, r for BMI and ln(CRP) was greater in women than men by 0.24 (CI, 0.09-0.37), and greater in North Americans/Europeans than Asians by 0.15 (CI, 0-0.28), on average. In North American/European children, the sex difference in r for BMI and ln(CRP) was 0.01 (CI, -0.08 to 0.06). Although limited to anthropometric measures, we found similar results when WC and WHR were used in the analyses. Obesity is associated with elevated levels of CRP and the association is stronger in women and North Americans/Europeans. The sex difference only emerges in adulthood.

Choi, J. H., S. N. Kim, et al. (2013). "Efficacy of the Pillar implant in the treatment of snoring and mild-to-moderate obstructive sleep apnea: a meta-analysis." Laryngoscope 123(1): 269-76.

OBJECTIVES/HYPOTHESIS: The Pillar implant is one of the surgical options for snoring and obstructive sleep apnea (OSA). It is designed to be inserted into the soft palate to reduce vibration and collapsibility. The efficacy of the Pillar implant has been evaluated in various studies. However, only one study conducted a meta-analysis of the findings, and was based on only three studies. We tried to get a more definite conclusion on the efficacy of the Pillar implant. STUDY DESIGN: Meta-analysis. METHODS: Efficacies were analyzed separately, one for snoring and the other for mild-to-moderate OSA. We searched MEDLINE, LILACS, SCOPUS, and the Cochrane Library. The key words "snoring AND implants" were used for snoring, and "apnea AND implants" for OSA. Seven studies for snoring and seven studies for mild-to-moderate OSA were finally included for meta-analysis. For snoring patients, a visual analogue scale that is scored by the bed partner was used to evaluate the loudness of the snoring sound. RESULTS: The Pillar implant reduced snoring sound significantly (standardized mean difference [SMD], -0.591; 95% confidence interval [CI], -0.753 to -0.429, P < .001). For mild-to-moderate OSA patients, the Pillar implant significantly reduced the Epworth Sleepiness Scale (SMD, -0.481; 95% CI, -0.606 to -0.358, P < .001), and apnea-hypopnea index (SMD, -0.378; 95% CI, -0.619 to -0.138, P = .002). Mean extrusion rate was 9.3% (95% CI, 7.0 to 12.2%). CONCLUSIONS: The present results indicate that the Pillar implant has a moderate effect on snoring and mild-to-moderate OSA. However, we need more studies with high level of evidence to arrive at a definite conclusion.

Choi, Y., B. Park, et al. (2013). "Body mass index and survival in patients with renal cell carcinoma: a clinical-based cohort and meta-analysis." Int J Cancer 132(3): 625-34.

Growing evidence suggests that obesity, an established cause of renal cell cancer (RCC), may also be associated with a better prognosis. To evaluate the association between RCC survival and obesity, we analyzed a large cohort of patients with RCC and undertook a meta-analysis of the published evidence. We collected clinical and pathologic data from 1,543 patients who underwent nephrectomy for RCC between 1994 and 2008 with complete follow-up through 2008. Patients were grouped according to BMI (kg/m(2) ): underweight <18.5, normal weight 18.5 to <23, overweight 23 to <25 and obese >/=25. We estimated survival using the Kaplan-Meier method and Cox proportional hazard models to examine the impact of BMI on overall survival (OS) and cancer-specific survival (CSS) with adjustment for covariates. We performed a meta-analysis of BMI and OS, CSS and recurrence-free survival (RFS) from all relevant studies using a random-effects model. The 5-year CSS increased from 76.1% in the lowest to 92.7% in the highest BMI category. A multivariate analysis showed higher OS [hazard ratio (HR) = 0.45; 95% CI: 0.29-0.68) and CSS (HR = 0.47; 95% CI: 0.29-0.77] in obese patients than in normal weight patients. The meta-analysis further corroborated that high BMI significantly improved OS (HR = 0.57; 95% CI: 0.43-0.76), CSS (HR = 0.59; 95% CI: 0.48-0.74) and RFS (HR = 0.49; 95% CI: 0.30-0.81). Our study shows that preoperative BMI is an independent prognostic indicator for survival among patients with RCC.

Choi, Y., S. Song, et al. (2013). "Consumption of red and processed meat and esophageal cancer risk: Meta-analysis." World J Gastroenterol 19(7): 1020-9.

To summarize the evidence about the association between red and processed meat intake and the risk of esophageal cancer, we systematically searched the PubMed and EMBASE databases up to May 2012, with a restriction to English publications, and the references of the retrieved articles. We combined the study-specific relative risks (RRs) and 95%CI, comparing the highest with the lowest categories of consumption by using a random-effects model. A total of 4 cohort studies and 23 case-control studies were included in the meta-analysis. The combined RRs (95%CI) of the cohort studies comparing the highest and lowest categories were 1.26 (1.00-1.59) for red meat and 1.25 (0.83-1.86) for processed meat. For the case-control studies, the combined RRs (95%CI) comparing the highest and lowest categories were 1.44 (1.16-1.80) for red meat and 1.36 (1.07-1.74) for processed meat. Findings from this meta-analysis suggest that a higher consumption of red meat was associated with a greater risk of esophageal cancer.

Choquet, H., J. Kasberger, et al. (2013). "Contribution of Common PCSK1 Genetic Variants to Obesity in 8,359 Subjects from Multi-Ethnic American Population." PLoS One 8(2): e57857.

Common variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI ( = 0.006) and obesity ( = 0.018) but also increased the obesity incidence during the 20 years of follow-up (HR = 1.53 [1.07-2.19], = 0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI ( = 0.028) and obesity ( = 0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR = 1.23 [1.05-1.45], = 9.5x10). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI ( = 4.2x10) and obesity ( = 3.4x10) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group ( = 0.756 and = 0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results suggest that the association of rs6232 with obesity may be age-dependent in European-Americans. However, multiple replication studies in multi-ethnic American population are needed to confirm our findings.

Chou, D., E. Abalos, et al. (2013). "Paracetamol/acetaminophen (single administration) for perineal pain in the early postpartum period." Cochrane Database Syst Rev 1: CD008407.

BACKGROUND: Perineal pain is a common but poorly studied adverse outcome following childbirth. Pain may result from perineal trauma due to bruising, spontaneous tears, surgical incisions (episiotomies), or in association with operative births (ventouse or forceps assisted births). OBJECTIVES: To determine the efficacy of a single administration of paracetamol (acetaminophen) systemic drugs used in the relief of acute postpartum perineal pain SEARCH METHODS: We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 6 November 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing paracetamol (acetaminophen) in a single dose compared with placebo for women with early postpartum perineal pain. We excluded quasi-RCTs and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors assessed each paper for inclusion and extracted data. One review author reviewed the decisions and confirmed calculations for pain relief scores. MAIN RESULTS: We did not identify any new trials from the updated search so the results remain unchanged as follows.We have included 10 studies describing two dosages of paracetamol. Of these, five studies (526 women) assessed 500 mg to 650 mg and six studies (841 women) assessed 1000 mg of paracetamol. We chose to use random-effects meta-analyses because of the heterogeneity in dosage used. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context.More women experienced pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89, 10 studies, 1279 women). In addition, there were significantly fewer women having additional pain relief with paracetamol compared with placebo (RR 0.34, 95% CI 0.21 to 0.55, eight studies, 1132 women). Both the 500 mg to 650 mg and 1000 mg doses were effective in providing more pain relief than placebo.Maternal and neonatal potential adverse drug effects were not assessed in any of the included studies. Indeed few secondary outcomes were assessed. AUTHORS' CONCLUSIONS: More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

Choubey, V. K., S. N. Sankhwar, et al. (2013). "Null genotypes at the GSTM1 and GSTT1 genes and the risk of benign prostatic hyperplasia: a case-control study and a meta-analysis." Prostate 73(2): 146-52.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age related non-malignant disease diagnosed as lower urinary tract symptoms and prostatic enlargement. Null genotypes in drug detoxification glutathione-S-transferase genes/enzymes, such as GSTT1 and GSTM1 have been reported to increase risk of several cancers including prostate. Meta-analysis on PC also suggested significant impact of GSTM1 null genotype but not that of GSTT1; however, BPH data have not been subjected to meta-analysis. METHODS: We investigated GSTT1 and GSTM1 genotypes in 429 subjects which included 244 BPH, 51 prostate cancer (PC) patients, and 134 control subjects to find if null genotype in any of the two genes increased the risk of BPH/PC. We also performed a quantitative meta-analysis on 888 BPH cases and 793 controls for GSTM1 and on 890 BPH cases and 793 controls for GSTT1 to assess overall consensus about the impact of null genotypes on BPH risk. RESULTS: We did not find any significant difference in the distribution of genotypes of either of the two genes between BPH/PC cases and controls; however, double deletion (GSTM1 null + GSTT1 null) increased BPH risk, significantly. Upon meta-analysis, null genotype of GSTM1 but not that of GSTT1 appeared to strongly affect BPH risk. CONCLUSIONS: In our population, null genotypes of either GSTM1 or GSTT1 do not appear to affect BPH risk; however, the double deletion was significantly associated with BPH. Meta-analysis suggested significant influence of GSTM1 null genotype but not that of GSTT1 on BPH risk.

Choueiri, T. K., Y. Je, et al. (2013). "Analgesic use and the risk of kidney cancer: A meta-analysis of epidemiologic studies." Int J Cancer.

Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for 3 categories of analgesics: acetaminophen, aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin, and 5 with other NSAIDs) that were performed in 6 countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR, 1.28; 95% CI, 1.15 to 1.44 and 1.25; 95% CI, 1.06 to 1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR, 1.10; 95% CI, 0.95 to 1.28), except for non-US studies (5 studies, pooled RR=1.17, 95% CI, 1.04 to 1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings.

Chu, A. Y., T. Workalemahu, et al. (2013). "Novel locus including FGF21 is associated with dietary macronutrient intake." Hum Mol Genet.

Dietary intake of macronutrients (carbohydrate, protein, and fat) has been associated with risk of chronic conditions such as obesity and diabetes. Family studies have reported a moderate contribution of genetics to variation in macronutrient intake. In a genome-wide meta-analysis of a population-based discovery cohort (n = 33 533), rs838133 in FGF21 (19q13.33), rs197273 near TRAF family member-associated NF-kappa-B activator (TANK) (2p24.2), and rs10163409 in FTO (16q12.2) were among the top associations (P < 10(-5)) for percentage of total caloric intake from protein and carbohydrate. rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Nutrition Working Group (n = 38 360) and attained genome-wide significance in combined analysis (P(joint) = 7.9 x 10(-9)). A cytokine involved in cellular metabolism, FGF21 is a potential susceptibility gene for obesity and type 2 diabetes. Our results highlight the potential of genetic variation for determining dietary macronutrient intake.

Chuang, S. K. (2013). "There Is Modest Evidence That Systemic Acyclovir or Valacyclovir Prevents Recurrent Herpes Labialis." J Evid Based Dent Pract 13(1): 16-17.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Effectiveness of antiviral agents for the prevention of recurrent herpes labialis: a systematic review and meta-analysis. Rahimi H, Mara T, Costella J, Speechley M, Bohay R. Oral Surg Oral Med Oral Pathol Oral Radiol 2012 May;113(5):618-27. REVIEWER: Sung-Kiang Chuang, DMD, MD, DMSc PURPOSE/QUESTION: To investigate the effectiveness of antiviral agents in the prevention of recurrent herpes labialis (RHL) SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade B: Inconsistent or limited-quality patient-oriented evidence.

Chun, C. A., K. S. Minor, et al. (2013). "Neurocognition in Psychometrically Defined College Schizotypy Samples: We Are NOT Measuring the "Right Stuff"." J Int Neuropsychol Soc: 1-14.

Although neurocognitive deficits are an integral characteristic of schizophrenia, there is inconclusive evidence as to whether they manifest across the schizophrenia-spectrum. We conducted two studies and a meta-analysis comparing neurocognitive functioning between psychometrically defined schizotypy and control groups recruited from a college population. Study One compared groups on measures of specific and global neurocognition, and subjective and objective quality of life. Study Two examined working memory and subjective cognitive complaints. Across both studies, the schizotypy group showed notably decreased subjective (d = 1.52) and objective (d = 1.02) quality of life and greater subjective cognitive complaints (d = 1.88); however, neurocognition was normal across all measures (d's < .35). Our meta-analysis of 33 studies examining neurocognition in at-risk college students revealed between-group differences in the negligible effect size range for most domains. The schizotypy group demonstrated deficits of a small effect size for working memory and set-shifting abilities. Although at-risk individuals report relatively profound neurocognitive deficits and impoverished quality of life, neurocognitive functioning assessed behaviorally is largely intact. Our data suggest that traditionally defined neurocognitive deficits do not approximate the magnitude of subjective complaints associated with psychometrically defined schizotypy. (JINS, 2013, 19, 1-14).

Chung, V. C., M. Chen, et al. (2013). "Add-on effect of chinese herbal medicine on mortality in myocardial infarction: systematic review and meta-analysis of randomized controlled trials." Evid Based Complement Alternat Med 2013: 675906.

In China, Chinese herbal medicine (CHM) is widely used as an adjunct to biomedicine (BM) in treating myocardial infarction (MI). This meta-analysis of RCTs evaluated the efficacy of combined CHM-BM in the treatment of MI, compared to BM alone. Sixty-five RCTs (12,022 patients) of moderate quality were identified. 6,036 patients were given CHM plus BM, and 5,986 patients used BM only. Combined results showed clear additional effect of CHM-BM treatment in reducing all-cause mortality (relative risk reduction (RRR) = 37%, 95% CI = 28%-45%, I(2) = 0.0%) and mortality of cardiac origin (RRR = 39%, 95% CI = 22%-52%, I(2) = 22.8). Benefits remained after random-effect trim and fill adjustment for publication bias (adjusted RRR for all-cause mortality = 29%, 95% CI = 16%-40%; adjusted RRR for cardiac death = 32%, 95% CI = 15%-46%). CHM is also found to be efficacious in lowering the risk of fatal and nonfatal cardiogenic shock, cardiac arrhythmia, myocardial reinfarction, heart failure, angina, and occurrence of total heart events. In conclusion, addition of CHM is very likely to be able to improve survival of MI patients who are already receiving BM. Further confirmatory evaluation via large blinded randomized trials is warranted.

Chutkan, N. B. (2013). "Surgical versus nonsurgical treatment of acute achilles tendon rupture: a meta-analysis of randomized trials." Orthopedics 36(2): 136-7.

Ciampi, R., C. Mian, et al. (2013). "Evidence of a low prevalence of RAS mutations in a large medullary thyroid cancer series." Thyroid 23(1): 50-7.

BACKGROUND: Approximately 60% of sporadic medullary thyroid carcinomas (sMTC) remain orphan of a recognized genetic cause. Recently, a high percentage of RAS point mutations have been described in RET-negative sMTC. The aim of this study was to assess the prevalence of RAS point mutations in a large series of MTC collected in four Italian centers. METHODS: For this purpose, we studied codons 12, 13, and 61 of H-, K-, and N-RAS genes in 188 MTC samples, either hereditary or sporadic, by direct sequencing. Correlations between the RAS mutational status and the clinical-pathological features of MTC patients as well as a meta-analysis of all published data were performed. RESULTS: The prevalence of RAS mutations in the present series of MTC was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumoral tissue, but not in peripheral blood indicating their somatic origin. A novel mutation in codon 72 (M72I) was found, but with a low or null transforming potential. No association was found between the presence of RAS mutations and the clinical-pathological features of the patients. Although not statistically significant, a positive association between the presence of RAS mutations and a better outcome was observed. The meta-analysis of all published studies confirmed a prevalence of 8.8% for RAS mutations in MTC. CONCLUSIONS: The prevalence of RAS mutations in our MTC series was relatively low and consistent with the meta-analysis data. Only somatic RAS mutations were found and only in RET-negative sMTC. Likewise, MTCs that harbor a RAS mutation identify a subgroup of tumors with less aggressive behavior. To our knowledge, this is the largest series of MTCs studied for the presence of mutations in RAS genes and the first meta-analysis on this specific topic.

Ciarrocca, M., M. V. Rosati, et al. (2013). "Is urinary 1-hydroxypyrene a valid biomarker for exposure to air pollution in outdoor workers? A meta-analysis." J Expo Sci Environ Epidemiol.

The aim of this study was to evaluate the usefulness and specificity of urinary 1-hydroxypyrene (1-OHPu) as a biomarker of the exposure from urban pollution to polycyclic aromatic hydrocarbons (PAHs) among outdoor workers in a meta-analysis. Our meta-analysis was performed according to standard methods, and the results show that the concentrations of 1-OHPu tend to be higher in exposed workers than in unexposed workers (if we exclude two highly heterogeneous articles), in exposed non-smokers than in unexposed non-smokers and in exposed than in unexposed workers who were carriers of the CYP1A1 genotype and in those with the glutathione-S-transferase M1 (-)genotype. These genotypes enhance the effect of exposure, particularly in non-smokers. Smoking reduces the differences between exposed and unexposed subjects. In conclusion, our results suggest that the use of the 1-OHPu biomarker appears to be reliable for studying occupational exposure to PAHs from urban pollution, as long as environmental and behavioural factors are considered.Journal of Exposure Science and Environmental Epidemiology advance online publication, 9 January 2013; doi:10.1038/jes.2012.111.

Cicero, A. F., F. Aubin, et al. (2013). "Do the lactotripeptides isoleucine-proline-proline and valine-proline-proline reduce systolic blood pressure in European subjects? A meta-analysis of randomized controlled trials." Am J Hypertens 26(3): 442-9.

BACKGROUND The milk-derived peptides isoleucine-proline-proline (IPP) and valine-proline- proline (VPP) have been shown to reduce systolic blood pressure (SBP). This decrease is convincingly shown in subjects of Asian origin, but less consistent results have been obtained in European populations. METHODS A meta-analysis was conducted in accord with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) requirements, to assess the effect of IPP and VPP on SBP in Europeans, and to explore some determinants of this effect. RESULTS Ninety-one publications on the effect of IPP and VPP on SBP in Europeans were identified, and 14 trials with 15 sets of data (n = 1,306) met the inclusion criteria for the meta-analysis. A random-effects model (using the restricted maximum likelihood (REML) estimator) was used for the analysis. Although not all individual trials showed a statistically significant effect of IPP or VPP in reducing SBP, the combination of all data for the two peptides yielded a statistically significantly greater effect for IPP/VPP than for placebo. The decrease in SBP with IPP/VPP was 1.28mm Hg (95% CI, -2.09 to -0.48, P = 0.0017) and the decrease in diastolic BP (DBP) was 0.59mm Hg (95% CI, -1.18 to -0.01, P = 0.047). There was no evidence in the meta-analysis of any publication bias or of heterogeneity (P = 0.13). Among other features, a significant effect was seen for age, with each additional year of age reducing the effect on SBP by 0.09mm Hg. This might be related to isolated systolic hypertension, a condition often encountered in the elderly, who may be poorly responsive to first-line treatments for hypertension. CONCLUSION The peptides IPP and VPP are effective in moderately reducing SBP in European subjects, as is known for Asian populations. These two peptides could therefore have a role in controlling blood pressure (BP), a prospect that merits their further study.

Ciliberto, D., C. Botta, et al. (2013). "Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomised trials." Eur J Cancer 49(3): 593-603.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Gemcitabine is the mainstay treatment for advanced disease. However, almost all up-to-date trials, that evaluated the benefit of gemcitabine-combination schedules, failed to demonstrate an improvement in overall survival (OS). In this study, we performed a systematic review and a meta-analysis of randomised clinical trials (RCTs) to investigate the efficacy and safety of gemcitabine-based combination regimens as compared to gemcitabine alone in the management of pancreatic cancer. METHODS: Clinical trials were collected by searching different databases (PubMed, Embase and the Central Registry of Controlled Trials of the Cochrane Library) and abstracts from major cancer meetings. We considered period ranging from January 1997 to January 2012. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates (TRs), were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model. FINDINGS: Thirty-four trials for a total of 10,660 patients were selected and included in the final analysis. The analysis showed that combination chemotherapy confers benefit in terms of OS (HR: 0.93; 95% confidence interval (CI): 0.89-0.97; p=0.001). ORs for both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.60, 95%CI: 0.47-0.76, p<0.001; OR for DCR: 0.79; 95%CI: 0.66-0.93; p=0.006). Toxicities were more frequent with the combination treatment and significance in terms of risk ratio was reached for diarrhoea (0.53, 95%CI: 0.36-0.79), nausea (0.74, 95%CI: 0.56-0.96), neutropenia (0.71, 95%CI: 0.59-0.85) and thrombocytopenia (0.57, 95%CI: 0.43-0.75). INTERPRETATION: The combination chemotherapy as compared to gemcitabine alone significantly improves OS in advanced pancreatic cancer (APC). However, this advantage is marginal whereas the treatment-related toxicity is increased, suggesting the use of gemcitabine-based combination regimens only in selected patient populations. New prospective trials, based on translational approaches and innovative validated biomarkers, are eagerly awaited on this topic.

Cini, C., A. Wolthuis, et al. (2013). "Peritoneal fluid cytokines and matrix-metalloproteinases as early markers of anastomotic leakage in colorectal anastomosis. A literature review and meta-analysis." Colorectal Dis.

AIM: There is recent interest in the measurement of peritoneal fluid cytokines in the early post operative period, to help diagnose anastomotic leakage at a preclinical stage. The currently available literature on the early diagnosis of colorectal anastomotic leakage by estimation of drain fluid cytokines or matrix metalloproteinases (MMP) is reviewed. METHOD: A literature search was performed in PubMed, Embase and the Cochrane library for all publications studying the feasibility to diagnose colorectal anastomotic leakage earlier, by estimation of peritoneal fluid cytokine or MMP levels. A meta-analysis of the most commonly measured cytokines was performed. RESULTS: Eight publications were included. Tumour necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) were most frequently studied. Most studies found significantly higher levels of TNF-alpha and IL-6 in patients with anastomotic leakage during the first three post-operative days. In the meta-analysis IL-6 levels were significantly higher from day 1 and TNF-alpha from day 2. MMP-9 was most often significantly elevated in patients with anastomotic leakage. CONCLUSION: Measurement of drain fluid cytokines and MMP has the potential to diagnose colorectal anastomotic leakage at a pre-clinical stage, but is not yet ready for clinical use. Further research is needed, possibly using IL-6 in combination with other cytokines and MMP as markers. (c) 2013 The Authors. Colorectal Disease (c) 2013 The Association of Coloproctology of Great Britain and Ireland.

Cirigliano, M. M. (2013). "Musical mnemonics in health science: A first look." Med Teach 35(3): e1020-6.

Song, with its memory enhancement potential and ability to engage, has been employed as a learning tool in some academic settings. Of the countless learning environments, health science may seem the most atypical setting for the musical mnemonic, and yet it may be the most suitable for its application. With medicine's robust history of student-made mnemonics, it only seems natural that learners and instructors alike have begun to experiment with song meant to educate and entertain, primarily imparting them through popular media-sharing sites. This initial assessment of song in health science is meant to highlight notions of efficacy, audience, and use through an informal survey of 10 user-made YouTube musical mnemonics. Two of these mnemonics were co-created by the author, while the remaining eight were identified via select search terms and significant viewer numbers. Resulting YouTube data infers that instructors play a major role in the use of musical mnemonics in health science education. User comments indicate that some students have found value in mnemonic songs, helping them recall information during assessments. More robust research methods, like Q-method, meta-analysis, and opinion mining, can further confirm the value and role of musical mnemonics as they pertain to medicine and healthcare.

Cirocchi, R., E. Farinella, et al. (2013). "Safety and efficacy of endoscopic colonic stenting as a bridge to surgery in the management of intestinal obstruction due to left colon and rectal cancer: A systematic review and meta-analysis." Surg Oncol 22(1): 14-21.

INTRODUCTION: Colorectal carcinoma can present with acute intestinal obstruction in 7%-30% of cases, especially if tumor is located at or distal to the splenic flexure. In these cases, emergency surgical decompression becomes mandatory as the traditional treatment option. It involves defunctioning stoma with or without primary resection of obstructing tumor. An alternative to surgery is endoluminal decompression. The aim of this review is to assess the effectiveness of colonic stents, used as a bridge to surgery, in the management of malignant left colonic and rectal obstruction. METHODS: We considered only randomized trials which compared stent vs surgery for intestinal obstruction from left sided colorectal cancer (as a bridge to surgery) irrespective of their size. No language or publication status restrictions were imposed. A systematic search was conducted in Medline, Cochrane Central Register of Controlled Trials and the Science Citation Index (from inception to December 2011) RESULTS: We identified 3109 citations through our electronic search and 3 through other sources. Initial screening of the titles and abstracts resulted in the exclusion of 3104 citations. A further 5 citations were excluded after detailed screening of full articles. Three published studies were included in this systematic review. A total of 197 patients were included in our analysis, 97 of them had colorectal stent vs 100 who had emergency surgery. Clinical success has been defined in different manners. In included trials the clinical success rate was significantly higher in the emergency surgery group (99%) compared with the stent group (52.5%) (p < 0.00001). There was no difference in the overall complication rate in the stent group (48.5%) vs emergency surgery group (51%) (p = 0.86). There was no difference in 30-days postoperative mortality (p = 0.97). The overall survival was analyzed in none trial. When used as a bridge to surgery, colorectal stents provide some advantages: the primary anastomosis rate was significantly higher in the stent group (64.9%) vs emergency surgery group (55%) (p = 0.003); the overall stoma rate was significantly lower in the stent group (45.3%) compared with the emergency surgery group (62%) (p = 0.02). There were no significant differences between the two groups as to permanent stoma rate (46.7% in stent group vs 51.8% in surgical group, p = 0.56), anastomotic leakage rate (9% in stent group vs 3.7% in surgical group, p = 0.35) and intra-abdominal abscess rate (5.1% in stent group vs 4.9% in surgical group, p = 0.97). CONCLUSION: Although colonic stenting appears to be an effective treatment of malignant large bowel obstruction, the clinical success resulted significantly higher in the emergency surgery group without any advantages in terms of overall complication rate and 30-days postoperative mortality. On the other hand, the colonic stenting as a bridge to surgery provides surgical advantages, as higher primary anastomosis rate and a lower overall stoma rate, without increasing the risk of anastomotic leak or intra-abdominal abscess. However, these results should be interpreted with caution because few studies reported data on these outcomes. Due to the small and variable sample size of the included trials, further RCTs are needed including a larger number of patients and evaluating long term results (overall survival and quality of life) and cost-effectiveness analysis.

Cirocchi, R., S. Trastulli, et al. (2013). "Minimally invasive necrosectomy versus conventional surgery in the treatment of infected pancreatic necrosis: a systematic review and a meta-analysis of comparative studies." Surg Laparosc Endosc Percutan Tech 23(1): 8-20.

AIM: : The purpose of this meta-analysis and systematic review is to compare minimally invasive necrosectomy (MIN) versus open necrosectomy (ON) surgery for infected necrosis of acute pancreatitis. METHODS: : One randomized controlled trial and 3 clinical controlled trials were selected, with a total of 336 patients (215 patients who underwent MIN and 121 patients underwent ON) included after searching in the following databases: Medline, Embase, Cochrane Central Register of Controlled Trials, BioMed Central, Science Citation Index (from inception to August 2011), Greynet, SIGLE (System for Information on Grey Literature in Europe), National Technological Information Service, British Library Integrated catalogue, and the Current Controlled Trials. Statistical analysis is performed using the odds ratio (OR) and weighted mean difference with 95% confidence interval (CI). RESULTS: : After the analysis of the data amenable to polling, significant advantages were found in favor of the MIN in terms of: incidence of multiple organ failure (OR, 0.16; 95% CI, 0.06-0.39) (P<0.0001), incisional hernias (OR, 0.23; 95% CI, 0.06-0.90) (P=0.03), new-onset diabetes (OR, 0.32; 95% CI, 0.12-0.88) (P=0.03), and for the use of pancreatic enzymes (OR, 0.005; 95% CI, 0.04-0.57) (P=0.005). No differences were found in terms of mortality rate (OR, 0.43; 95% CI, 0.18-1.05) (P=0.06), multiple systemic complications (OR, 0.34; 95% CI, 0.01-8.60) (P=0.51), surgical reintervention for further necrosectomy (OR, 0.16; 95% CI, 0.00-3.07) (P=0.19), intra-abdominal bleeding (OR, 0.79; 95% CI, 0.41-1.50) (P=0.46), enterocutaneous fistula or perforation of visceral organs (OR, 0.52; 95% CI, 0.27-1.00) (P=0.05), pancreatic fistula (OR, 0.66; 95% CI, 0.30-1.46) (P=0.30), and surgical reintervention for postoperative complications (OR, 0.50; 95% CI, 0.23-1.08) (P=0.08). CONCLUSIONS: : The lack of comparative studies and high heterogeneity of the data present in the literature did not permit to draw a definitive conclusion on this topic. The results of the present meta-analysis might be helpful to design future high-powered randomized studies that compare MIN with ON for acute necrotizing pancreatitis.

Cirocchi, R., S. Trastulli, et al. (2013). "Intracorporeal versus extracorporeal anastomosis during laparoscopic right hemicolectomy - Systematic review and meta-analysis." Surg Oncol 22(1): 1-13.

BACKGROUND: Since 2005, after an initial scanty spreading, the vast majority of surgeons advice against the intracorporeal ileocolic anastomosis following right hemicolectomies. In the subsequent years, greater interest was re-discovered for the intracorporeal ileocolic anastomosis formed after video-assisted right hemicolectomies OBJECTIVE: The aim of this systematic review is to compare the intra-abdominal versus extra-abdominal anastomosis after right laparoscopic colectomy. DATA SOURCES: A systematic search was conducted in Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, BioMed Central and the Science Citation Index. STUDY SELECTION: A total of 191 publications were identified; seven non-randomized studies published between 2004 and 2012 with a total of 945 patients, who underwent laparoscopic right colectomy for malignant and benign disease, were included in this systematic review. Intervention: Intra-abdominal versus extra-abdominal confectioning of ileo-coloc anastomosis after right laparoscopic colectomy. MAIN OUTCOME MEASURES: Anastomotic leak, overall post-operative morbidity and overall 30-days post-operative mortality. RESULTS: Anastomotic leak rate resulted similar in IA (1.13%) and EA (1.84%) group (P=0.81, OR of 0.90, 95% CI 0.24-3.10) (Chi(2)=3.90, P=0.42, I(2)=0%). The mortality rate was lower in the IA group (0.34% versus 1.32%), although no statistically difference was demonstrated between the two groups (P = 0.48, OR of 0.52 95% CI 0.09-3.10). It was not possible to conduct a meta-analysis of post-operative morbidity as the data reported in the included studies were too heterogeneous. LIMITATIONS: The weakness in our results was due to the lack of evidence in current published literature. CONCLUSIONS: The present systematic review of literature and meta-analysis failed to solve the controversies between intracorporeal and extracorporeal anastomosis after laparoscopic right hemicolectomy. Future randomized, controlled trials are needed to further evaluate different surgical anastomosis after laparoscopic right hemicolectomy.

Clancy, C., J. P. Burke, et al. (2013). "KRAS mutation does not predict the efficacy of neo-adjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis." Surg Oncol.

INTRODUCTION: The current management of locally advanced rectal cancer involves total mesorectal excision, which may be preceded by neo-adjuvant chemoradiotherapy (CRT). Individual patient response to CRT is variable and reproducible biomarkers of response are needed. The role of the V-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) in rectal cancer remains equivocal. The aim of the current study was to systematically appraise the effect of KRAS mutation on outcomes following CRT for rectal cancer. METHODS: A comprehensive search for published studies examining the effect of KRAS mutation on outcome after neo-adjuvant CRT in rectal cancer was performed. Each study was reviewed and data extracted. Random-effects methods were used to combine data. RESULTS: Data was retrieved from 8 series describing 696 patients. Neo-adjuvant treatment regimens varied in usage of chemotherapeutic agents and interval to surgery. KRAS mutation was present in an average of 33.2 +/- 11.8% of patients with rectal cancer. KRAS mutation was not associated with decreased rates of pathological complete response (odds ratio (OR): 0.778, 95% confidence interval (CI): 0.424-1.428, P = 0.418), tumor down-staging (OR: 0.846, 95% CI: 0.331-2.162, P = 0.728) or an increase in cancer related mortality (OR: 1.239, 95% CI: 0.607-2.531, P = 0.555). CONCLUSIONS: Based on these data, the presence of KRAS mutation does not affect tumor down-staging or cancer specific survival following neo-adjuvant CRT and surgery for rectal cancer.

Clark, D. A. (2013). "Do anti-TNF-alpha drugs increase cancer risk in rheumatoid arthritis patients?" Inflammopharmacology 21(2): 125-7.

Concern has been raised about an increased risk of lymphoma and skin cancers in patients with rheumatoid arthritis due to administration of anti-TNF-alpha drugs. Meta-analysis of observational data from registries as well as from randomized controlled trials has failed to show a significant increase in the risk of lymphoma when the sample size has been sufficiently large; skin cancer risk may represent a valid concern. Issues relating to interpretation of these data are discussed.

Cleland, V., A. Granados, et al. (2013). "Effectiveness of interventions to promote physical activity among socioeconomically disadvantaged women: a systematic review and meta-analysis." Obes Rev 14(3): 197-212.

Physical activity is important for preventing weight gain and obesity, but women experiencing socioeconomic disadvantage are at high risk of inactivity. This study aimed to determine the effectiveness of interventions to increase physical activity among women experiencing disadvantage, and the intervention factors (i.e. physical activity measure, delivery mode, delivery channel, setting, duration, use of theory, behavioural techniques, participant age, risk of bias) associated with effectiveness. We conducted a meta-analysis of controlled trials using random-effects models and meta-regression. Seven databases were searched for trials among healthy women (18-64 years), which included a physical activity intervention, any control group, and statistical analyses of a physical activity outcome at baseline and post-intervention. Nineteen studies were included (n = 6,339). Because of substantial statistical heterogeneity (chi(2) = 53.61, df = 18, P < 0.0001, I(2) = 66%), an overall pooled effect is not reported. In subgroup analyses, between-group differences were evident for delivery mode, which modestly reduced heterogeneity (to 54%). Studies with a group delivery component had a standardized mean difference of 0.38 greater than either individual or community-based delivery. Programs with a group delivery mode significantly increase physical activity among women experiencing disadvantage, and group delivery should be considered an essential element of physical activity promotion programs targeting this population group.

Cochrane, C. J. and K. P. Ebmeier (2013). "Diffusion tensor imaging in parkinsonian syndromes: A systematic review and meta-analysis." Neurology 80(9): 857-64.

OBJECTIVES: We performed a systematic review to assess alterations in measures of diffusion tensor imaging (DTI) in parkinsonian syndromes, exploring the potential role of DTI in diagnosis and as a candidate biomarker. METHODS: We searched EMBASE and Medline databases for DTI studies comparing parkinsonian syndromes or related dementias with controls or another defined parkinsonian syndrome. Key details for each study regarding participants, imaging methods, and results were extracted. Estimates were pooled, where appropriate, by random-effects meta-analysis. RESULTS: Of 333 results, we identified 43 studies suitable for inclusion (958 patients, 764 controls). DTI measures detected alterations in all parkinsonian syndromes, with distribution varying differentially with disease type. Nine studies were included in a meta-analysis of the substantia nigra in Parkinson disease. A notable effect size was found for lowered fractional anisotropy in the substantia nigra for patients with Parkinson disease vs controls (-0.639, 95% confidence interval -0.860 to -0.417, p < 0.0001). CONCLUSION: DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis. Larger cohort studies are required to investigate some encouraging preliminary findings. Given the complexity of the parkinsonian syndromes, it is likely that any potential DTI biomarker would be used in combination with other relevant biomarkers.

Cohen, D., M. B. Bogeat-Triboulot, et al. (2013). "Developmental and Environmental Regulation of Aquaporin Gene Expression across Populus Species: Divergence or Redundancy?" PLoS One 8(2): e55506.

Aquaporins (AQPs) are membrane channels belonging to the major intrinsic proteins family and are known for their ability to facilitate water movement. While in Populus trichocarpa, AQP proteins form a large family encompassing fifty-five genes, most of the experimental work focused on a few genes or subfamilies. The current work was undertaken to develop a comprehensive picture of the whole AQP gene family in Populus species by delineating gene expression domain and distinguishing responsiveness to developmental and environmental cues. Since duplication events amplified the poplar AQP family, we addressed the question of expression redundancy between gene duplicates. On these purposes, we carried a meta-analysis of all publicly available Affymetrix experiments. Our in-silico strategy controlled for previously identified biases in cross-species transcriptomics, a necessary step for any comparative transcriptomics based on multispecies design chips. Three poplar AQPs were not supported by any expression data, even in a large collection of situations (abiotic and biotic constraints, temporal oscillations and mutants). The expression of 11 AQPs was never or poorly regulated whatever the wideness of their expression domain and their expression level. Our work highlighted that PtTIP1;4 was the most responsive gene of the AQP family. A high functional divergence between gene duplicates was detected across species and in response to tested cues, except for the root-expressed PtTIP2;3/PtTIP2;4 pair exhibiting 80% convergent responses. Our meta-analysis assessed key features of aquaporin expression which had remained hidden in single experiments, such as expression wideness, response specificity and genotype and environment interactions. By consolidating expression profiles using independent experimental series, we showed that the large expansion of AQP family in poplar was accompanied with a strong divergence of gene expression, even if some cases of functional redundancy could be suspected.

Coleman, S., C. Gorecki, et al. (2013). "Patient risk factors for pressure ulcer development: Systematic review." Int J Nurs Stud.

OBJECTIVE: To identify risk factors independently predictive of pressure ulcer development in adult patient populations? DESIGN: A systematic review of primary research was undertaken, based upon methods recommended for effectiveness questions but adapted to identify observational risk factor studies. DATA SOURCES: Fourteen electronic databases were searched, each from inception until March 2010, with hand searching of specialist journals and conference proceedings; contact with experts and a citation search. There was no language restriction. REVIEW METHODS: Abstracts were screened, reviewed against the eligibility criteria, data extracted and quality appraised by at least one reviewer and checked by a second. Where necessary, statistical review was undertaken. We developed an assessment framework and quality classification based upon guidelines for assessing quality and methodological considerations in the analysis, meta-analysis and publication of observational studies. Studies were classified as high, moderate, low and very low quality. Risk factors were categorised into risk factor domains and sub-domains. Evidence tables were generated and a summary narrative synthesis by sub-domain and domain was undertaken. RESULTS: Of 5462 abstracts retrieved, 365 were identified as potentially eligible and 54 fulfilled the eligibility criteria. The 54 studies included 34,449 patients and acute and community patient populations. Seventeen studies were classified as high or moderate quality, whilst 37 studies (68.5%) had inadequate numbers of pressure ulcers and other methodological limitations. Risk factors emerging most frequently as independent predictors of pressure ulcer development included three primary domains of mobility/activity, perfusion (including diabetes) and skin/pressure ulcer status. Skin moisture, age, haematological measures, nutrition and general health status are also important, but did not emerge as frequently as the three main domains. Body temperature and immunity may be important but require further confirmatory research. There is limited evidence that either race or gender is important. CONCLUSIONS: Overall there is no single factor which can explain pressure ulcer risk, rather a complex interplay of factors which increase the probability of pressure ulcer development. The review highlights the limitations of over-interpretation of results from individual studies and the benefits of reviewing results from a number of studies to develop a more reliable overall assessment of factors which are important in affecting patient susceptibility.

Collaborators, R., M. J. Bown, et al. (2013). "Surveillance intervals for small abdominal aortic aneurysms: a meta-analysis." JAMA 309(8): 806-13.

IMPORTANCE: Small abdominal aortic aneurysms (AAAs [3.0 cm-5.4 cm in diameter]) are monitored by ultrasound surveillance. The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture. OBJECTIVE: To limit risk of aneurysm rupture or excessive growth by optimizing ultrasound surveillance intervals. DATA SOURCES AND STUDY SELECTION: Individual patient data from studies of small AAA growth and rupture were assessed. Studies were identified for inclusion through a systematic literature search through December 2010. Study authors were contacted, which yielded 18 data sets providing repeated ultrasound measurements of AAA diameter over time in 15,471 patients. DATA EXTRACTION: AAA diameters were analyzed using a random-effects model that allowed for between-patient variability in size and growth rate. Rupture rates were analyzed by proportional hazards regression using the modeled AAA diameter as a time-varying covariate. Predictions of the risks of exceeding 5.5-cm diameter and of rupture within given time intervals were estimated and pooled across studies by random effects meta-analysis. RESULTS: AAA growth and rupture rates varied considerably across studies. For each 0.5-cm increase in AAA diameter, growth rates increased on average by 0.59 mm per year (95% CI, 0.51-0.66) and rupture rates increased by a factor of 1.91 (95% CI, 1.61-2.25). For example, to control the AAA growth risk in men of exceeding 5.5 cm to below 10%, on average, a 7.4-year surveillance interval (95% CI, 6.7-8.1) is sufficient for a 3.0-cm AAA, while an 8-month interval (95% CI, 7-10) is necessary for a 5.0-cm AAA. To control the risk of rupture in men to below 1%, the corresponding estimated surveillance intervals are 8.5 years (95% CI, 7.0-10.5) and 17 months (95% CI, 14-22). CONCLUSION AND RELEVANCE: In contrast to the commonly adopted surveillance intervals in current AAA screening programs, surveillance intervals of several years may be clinically acceptable for the majority of patients with small AAA.

Collins, P. F., M. Elia, et al. (2013). "Nutritional support and functional capacity in chronic obstructive pulmonary disease: a systematic review and meta-analysis." Respirology.

Currently there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCTs (n = 448) in stable COPD patients investigating the effects of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 10 RCTs), enteral tube feeding (1 RCT)] versus control on functional outcomes. Meta-analysis of the changes induced by intervention found that whilst respiratory function (FEV(1,) lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (PI max +3.86 SE 1.89 cm H(2) O, P = 0.041; PE max +11.85 SE 5.54 cm H(2) O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved, and associated with weight gains of >/= 2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta-analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta-analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements in nutritional intake and weight.

Comer, J. S., C. Chow, et al. (2013). "Psychosocial treatment efficacy for disruptive behavior problems in very young children: a meta-analytic examination." J Am Acad Child Adolesc Psychiatry 52(1): 26-36.

OBJECTIVE: Service use trends showing increased off-label prescribing in very young children and reduced psychotherapy use raise concerns about quality of care for early disruptive behavior problems. Meta-analysis can empirically clarify best practices and guide clinical decision making by providing a quantitative synthesis of a body of literature, identifying the magnitude of overall effects across studies, and determining systematic factors associated with effect variations. METHOD: We used random-effects meta-analytic procedures to empirically evaluate the overall effect of psychosocial treatments on early disruptive behavior problems, as well as potential moderators of treatment response. Thirty-six controlled trials, evaluating 3,042 children, met selection criteria (mean sample age, 4.7 years; 72.0% male; 33.1% minority youth). RESULTS: Psychosocial treatments collectively demonstrated a large and sustained effect on early disruptive behavior problems (Hedges' g = 0.82), with the largest effects associated with behavioral treatments (Hedges' g = 0.88), samples with higher proportions of older and male youth, and comparisons against treatment as usual (Hedges' g = 1.17). Across trials, effects were largest for general externalizing problems (Hedges' g = 0.90) and problems of oppositionality and noncompliance (Hedges' g = 0.76), and were weakest, relatively speaking, for problems of impulsivity and hyperactivity (Hedges' g = 0.61). CONCLUSIONS: In the absence of controlled trials evaluating psychotropic interventions, findings provide robust quantitative support that psychosocial treatments should constitute first-line treatment for early disruptive behavior problems. Against a backdrop of concerning trends in the availability and use of supported interventions, findings underscore the urgency of improving dissemination efforts for supported psychosocial treatment options, and removing systematic barriers to psychosocial care for affected youth.

Conde-Agudelo, A., A. Papageorghiou, et al. (2013). "Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta-analysis." BJOG.

BACKGROUND: Several biomarkers for predicting intrauterine growth restriction (IUGR) have been proposed in recent years. However, the predictive performance of these biomarkers has not been systematically evaluated. OBJECTIVE: To determine the predictive accuracy of novel biomarkers for IUGR in women with singleton gestations. SEARCH STRATEGY: Electronic databases, reference list checking and conference proceedings. SELECTION CRITERIA: Observational studies that evaluated the accuracy of novel biomarkers proposed for predicting IUGR. DATA COLLECTION AND ANALYSIS: Data were extracted on characteristics, quality and predictive accuracy from each study to construct 2 x 2 tables. Summary receiver operating characteristic curves, sensitivities, specificities and likelihood ratios (LRs) were generated. MAIN RESULTS: A total of 53 studies, including 39 974 women and evaluating 37 novel biomarkers, fulfilled the inclusion criteria. Overall, the predictive accuracy of angiogenic factors for IUGR was minimal (median pooled positive and negative LRs of 1.7, range 1.0-19.8; and 0.8, range 0.0-1.0, respectively). Two small case-control studies reported high predictive values for placental growth factor and angiopoietin-2 only when IUGR was defined as birthweight centile with clinical or pathological evidence of fetal growth restriction. Biomarkers related to endothelial function/oxidative stress, placental protein/hormone, and others such as serum levels of vitamin D, urinary albumin : creatinine ratio, thyroid function tests and metabolomic profile had low predictive accuracy. CONCLUSIONS: None of the novel biomarkers evaluated in this review are sufficiently accurate to recommend their use as predictors of IUGR in routine clinical practice. However, the use of biomarkers in combination with biophysical parameters and maternal characteristics could be more useful and merits further research.

Conde-Agudelo, A., R. Romero, et al. (2013). "Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis." Am J Obstet Gynecol 208(1): 42 e1-42 e18.

OBJECTIVE: No randomized controlled trial has compared vaginal progesterone and cervical cerclage directly for the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. STUDY DESIGN: Adjusted indirect metaanalysis of randomized controlled trials. RESULTS: Four studies that evaluated vaginal progesterone vs placebo (158 patients) and 5 studies that evaluated cerclage vs no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth at <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect metaanalyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes. CONCLUSION: Based on state-of-the-art methods for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous preterm birth. Selection of the optimal treatment needs to consider adverse events, cost and patient/clinician preferences.

Confalonieri, M., D. Annane, et al. (2013). "Is Prolonged Low-Dose Glucocorticoid Treatment Beneficial in Community-Acquired Pneumonia?" Curr Infect Dis Rep.

Community-acquired pneumonia (CAP) has a significant impact on public health in terms of short-term and long-term morbidity and mortality. Irrespective of microbiological etiology, the host's inability to fully downregulate systemic inflammation is the dominant pathogenetic process contributing to acute and long-term morbidity and mortality in CAP. Glucocorticoids are the natural regulators of inflammation, and their production increases during infection. There is consistent evidence that downregulation of systemic inflammation with prolonged low-dose glucocorticoid treatment in patients with severe sepsis and acute respiratory distress syndrome improves cardiovascular and pulmonary organ physiology. A recent meta-analysis of pooled controlled small trials (n = 970) of patients admitted with CAP found improved short-term mortality in the subgroup with severe CAP and/or receiving >5 days of glucocorticoid treatment. We have expanded on this meta-analysis by including patients with CAP recruited in trials investigating prolonged low-dose glucocorticoid treatment in septic shock and/or early acute respiratory distress syndrome (n = 1,206). Our findings confirm a survival advantage for severe CAP (RR 0.66, 95% confidence interval 0.51-0.84; p = .001). A large randomized trial is in progress to confirm the aggregate findings of these small trials and to evaluate the long-term effect of this low-cost treatment.

Connolly, B. J., L. A. Pearce, et al. (2013). "Aspirin Therapy and Risk of Subdural Hematoma: Meta-analysis of Randomized Clinical Trials." J Stroke Cerebrovasc Dis.

BACKGROUND: Subdural hematomas are an important bleeding complication of antithrombotic therapies. We sought to characterize the risk of subdural hematoma associated with antiplatelet therapy. METHODS: Trials were gathered from the Cochrane Central Register of Controlled Trials and from recent meta-analyses of trials regarding antiplatelet therapy for the primary prevention of stroke. Randomized trials published since 1980 comparing antiplatelet therapy with placebo or control and reporting subdural hematoma were included in the analysis. For recent large trials that did not report subdural hematomas, unpublished results were sought. Two reviewers independently extracted data on study design and subdural hematomas, with differences resolved by joint review and consensus. RESULTS: Four published trials were identified that compared aspirin with placebo/control involving 6565 participants (mean age 66 years) with 8 total subdural hematomas. Unpublished data from 5 aspirin trials with 90,689 participants reported 18 total subdural hematomas. The incidence of subdural hematomas varied from 0.02 per 1000 patient-years for primary prevention trials of middle-aged health professionals to 1 to 2 per 1000 patient-years for older patients with atrial fibrillation. Pooled data from all 9 trials revealed an odds ratio of 1.6 (95% confidence interval 0.8-3.5; heterogeneity P = .8; I(2) index 0%) for antiplatelet therapy and risk of subdural hematoma. CONCLUSIONS: Based on the limited available data, it is uncertain whether aspirin therapy increases the risk of subdural hematoma: the observed 1.6-fold increased risk was not statistically significant. The incidence of subdural hematoma during aspirin therapy is low but varies widely depending upon the age of the patient population.

Consortium, A., K. B. Ahmeti, et al. (2013). "Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1." Neurobiol Aging 34(1): 357 e7-19.

Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. Individuals with ALS rapidly progress to paralysis and die from respiratory failure within 3 to 5 years after symptom onset. Epidemiological factors explain only a modest amount of the risk for ALS. However, there is growing evidence of a strong genetic component to both familial and sporadic ALS risk. The International Consortium on Amyotrophic Lateral Sclerosis Genetics was established to bring together existing genome-wide association cohorts and identify sporadic ALS susceptibility and age at symptom onset loci. Here, we report the results of a meta-analysis of the International Consortium on Amyotrophic Lateral Sclerosis Genetics genome-wide association samples, consisting of 4243 ALS cases and 5112 controls from 13 European ancestry cohorts from across the United States and Europe. Eight genomic regions provided evidence of association with ALS, including 9p21.2 (rs3849942, odds ratio [OR] = 1.21; p = 4.41 x 10(-7)), 17p11.2 (rs7477, OR = 1.30; p = 2.89 x 10(-7)), and 19p13 (rs12608932, OR = 1.37, p = 1.29 x 10(-7)). Six genomic regions were associated with age at onset of ALS. The strongest evidence for an age of onset locus was observed at 1p34.1, with comparable evidence at rs3011225 (R(2)(partial) = 0.0061; p = 6.59 x 10(-8)) and rs803675 (R(2)(partial) = 0.0060; p = 6.96 x 10(-8)). These associations were consistent across all 13 cohorts. For rs3011225, individuals with at least 1 copy of the minor allele had an earlier average age of onset of over 2 years. Identifying the underlying pathways influencing susceptibility to and age at onset of ALS may provide insight into the pathogenic mechanisms and motivate new pharmacologic targets for this fatal neurodegenerative disease.

Cook, D. A., S. J. Hamstra, et al. (2013). "Comparative effectiveness of instructional design features in simulation-based education: systematic review and meta-analysis." Med Teach 35(1): e867-98.

BACKGROUND: Although technology-enhanced simulation is increasingly used in health professions education, features of effective simulation-based instructional design remain uncertain. AIMS: Evaluate the effectiveness of instructional design features through a systematic review of studies comparing different simulation-based interventions. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL, ERIC, PsycINFO, Scopus, key journals, and previous review bibliographies through May 2011. We included original research studies that compared one simulation intervention with another and involved health professions learners. Working in duplicate, we evaluated study quality and abstracted information on learners, outcomes, and instructional design features. We pooled results using random effects meta-analysis. RESULTS: From a pool of 10,903 articles we identified 289 eligible studies enrolling 18,971 trainees, including 208 randomized trials. Inconsistency was usually large (I2 > 50%). For skills outcomes, pooled effect sizes (positive numbers favoring the instructional design feature) were 0.68 for range of difficulty (20 studies; p < 0.001), 0.68 for repetitive practice (7 studies; p = 0.06), 0.66 for distributed practice (6 studies; p = 0.03), 0.65 for interactivity (89 studies; p < 0.001), 0.62 for multiple learning strategies (70 studies; p < 0.001), 0.52 for individualized learning (59 studies; p < 0.001), 0.45 for mastery learning (3 studies; p = 0.57), 0.44 for feedback (80 studies; p < 0.001), 0.34 for longer time (23 studies; p = 0.005), 0.20 for clinical variation (16 studies; p = 0.24), and -0.22 for group training (8 studies; p = 0.09). CONCLUSIONS: These results confirm quantitatively the effectiveness of several instructional design features in simulation-based education.

Cook, R. C., M. H. Yamashita, et al. (2013). "Prophylactic magnesium does not prevent atrial fibrillation after cardiac surgery: a meta-analysis." Ann Thorac Surg 95(2): 533-41.

BACKGROUND: Atrial fibrillation (AF) is a common complication after cardiac surgery. Previous meta-analyses have concluded prophylactic magnesium (Mg) prevents postoperative AF, although with a significant degree of heterogeneity among included studies. Recently, the largest randomized, controlled trial published to date (but not included in prior published meta-analyses) concluded that Mg sulfate is not protective against AF after cardiac surgery. The objective of this study was to conduct a new meta-analysis including the results of new Mg trials not included in previous meta-analyses, and to investigate the potential causes and effects of significant heterogeneity observed in previously published meta-analyses. METHODS: The MEDLINE, EMBASE, and CENTRAL databases were searched for relevant studies published up to March 31, 2012. Pooled odds ratios of occurrence of AF were calculated using random-effects models. Heterogeneity was assessed as significant using the I(2) statistic. RESULTS: Egger's and funnel plots demonstrated biases toward stronger and more positive effects of Mg in smaller studies. When the analysis was restricted to the five double-blind, intention-to-treat studies in which AF was the primary outcome (Mg arm, n = 710; control arm, n = 713), Mg did not prevent postoperative AF (odds ratio, 0.94; p = 0.77), and heterogeneity was no longer significant (I(2) = 40%; p = 0.15). CONCLUSIONS: This meta-analysis, restricted to well-conducted trials, does not support the prophylactic use of Mg to prevent AF after cardiac surgery. Prior meta-analyses have drawn conclusions from simple random-effects models with significant heterogeneity. However, this approach leaves important residual heterogeneity and overemphasizes the strongly positive effects of smaller studies.

Cooper, C., R. Lester, et al. (2013). "Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis." QJM 106(2): 153-63.

BACKGROUND: New direct-acting antiviral agents for hepatitis C genotype 1 infection, boceprevir and telaprevir, offer enhanced sustained virologic response (SVR) among both treatment-naive and treatment-experienced patients. AIM: To determine the relative efficacy of the new direct-acting antiviral agents by applying a multiple treatment comparison meta-analysis. DESIGN: We included published Phase II and III randomized controlled trials evaluating head-to-head comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment comparison meta-analysis. RESULTS: We included data from four boceprevir, three telaprevir and six peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin randomized controlled trials. Both boceprevir and telaprevir offer statistically superior outcomes for SVR, relapse and discontinuation due to adverse events than either peg-interferons among both treatment-naive and treatment-experienced patients. Among treatment-naive patients, clinical outcomes were similar for boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval (95% CrI) 0.41-1.91] and for relapse (OR 1.09, 95% CrI 0.19-4.84). Similarly, among treatment-experienced patients, clinical outcomes were similar for boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70-3.08) and for relapse (OR 0.35, 95% CrI 0.13-1.02). For treatment-naive patients receiving standard-duration therapy, telaprevir yielded lower rates of anemia and neutropenia, but higher rates of rash and pruritus. For treatment-experience patients, all adverse event rates were higher with telaprevir. DISCUSSION: Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1 treatment-naive and treatment-experienced patients.

Cooper, C., N. Mukadam, et al. (2013). "Systematic Review of the Effectiveness of Pharmacologic Interventions to Improve Quality of Life and Well-being in People With Dementia." Am J Geriatr Psychiatry 21(2): 173-83.

OBJECTIVE: To review systematically, for the first time, the effectiveness of all pharmacologic interventions to improve quality of life and well-being in people with dementia. DESIGN: Systematic review and meta-analysis. METHODS: We systematically reviewed the 15 randomized controlled trials and one review that fitted predetermined criteria. We included studies that reported the outcomes quality of life, well-being, happiness, or pleasure. MEASUREMENTS: We rated the validity of studies using a checklist. We calculated mean differences between intervention and control groups at follow-up. RESULTS: None of the evaluated trials reported a significant benefit to quality of life or well-being for people with dementia when comparing those taking a drug or its comparator at follow-up (pooled weighted mean difference: 0.18 [95% confidence interval: -0.82 to 0.46]). CONCLUSION: We found no consistent evidence that any drug improves quality of life in people with dementia. We recommend that all dementia trials should include quality of life as an outcome, as this is important to patients, and cannot be presumed from improvements in cognition or other symptomatic outcomes, especially if the latter are small.

Coren, E., R. Hossain, et al. (2013). "Interventions for promoting reintegration and reducing harmful behaviour and lifestyles in street-connected children and young people." Cochrane Database Syst Rev 2: CD009823.

BACKGROUND: Numbers of street-connected children and young people run into many millions worldwide and include children and young people who live or work in street environments. Whether or not they remain connected to their families of origin, and despite many strengths and resiliencies, they are vulnerable to a range of risks and are excluded from mainstream social structures and opportunities. OBJECTIVES: To summarise the effectiveness of interventions for street-connected children and young people that promote inclusion and reintegration and reduce harms. To explore the processes of successful intervention and models of change in this area, and to understand how intervention effectiveness may vary in different contexts.. SEARCH METHODS: We searched the following bibliographic databases, from inception to 2012, and various relevant non-governmental and organisational websites: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE and PreMEDLINE; EMBASE and EMBASE Classic; CINAHL; PsycINFO; ERIC; Sociological Abstracts; Social Services Abstracts; Social Work Abstracts; Healthstar; LILACS; System for Grey literature in Europe (OpenGrey); ProQuest Dissertations and Theses; EconLit; IDEAS Economics and Finance Research; JOLIS Library Catalog of the holdings of the World Bank Group and IMF Libraries; BLDS (British Library for Development Studies); Google, Google Scholar. SELECTION CRITERIA: The review included data from harm reduction or reintegration promotion intervention studies that used a comparison group study design and were all randomised or quasi-randomised studies. Studies were included if they evaluated interventions aimed to benefit street-connected children and young people, aged 0 to 24 years, in all contexts. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of included studies. Data were extracted on intervention delivery, context, process factors, equity and outcomes. Outcome measures were grouped according to whether they measured psychosocial outcomes, risky sexual behaviours or substance use. A meta-analysis was conducted for some outcomes though it was not possible for all due to differences in measurements between studies. Other outcomes were evaluated narratively. MAIN RESULTS: We included 11 studies evaluating 12 interventions from high income countries. We did not find any sufficiently robust evaluations conducted in low and middle income countries (LMICs) despite the existence of many relevant programmes. Study quality overall was low to moderate and there was great variation in the measurement used by studies, making comparison difficult. Participants were drop-in and shelter based. We found no consistent results on a range of relevant outcomes within domains of psychosocial health, substance misuse and sexual risky behaviours despite the many measurements collected in the studies. The interventions being evaluated consisted of time limited therapeutically based programmes which did not prove more effective than standard shelter or drop-in services for most outcomes and in most studies. There were favourable changes from baseline in outcomes for most particpants in therapy interventions and also in standard services. There was considerable heterogeneity between studies and equity data were inconsistently reported. No study measured the primary outcome of reintegration or reported on adverse effects. The review discussion section included consideration of the relevance of the findings for LMIC settings. AUTHORS' CONCLUSIONS: Analysis across the included studies found no consistently significant benefit for the 'new' interventions compared to standard services for street-connected children and young people. These latter interventions, however, have not been rigorously evaluated, especially in the context of LMICs. Robustly evaluating the interventions would enable better recommendations to be made for service delivery. There is a need for future research in LMICs that includes children who are on the streets due to urbanisation, war or migration and who may be vulnerable to risks such as trafficking.

Cornelissen, V. A., R. Buys, et al. (2013). "Endurance exercise beneficially affects ambulatory blood pressure: a systematic review and meta-analysis." J Hypertens 31(4): 639-48.

Exercise is widely recommended as one of the key preventive lifestyle changes to reduce the risk of hypertension and to manage high blood pressure (BP), but individual studies investigating the effect of exercise on ambulatory BP have remained inconclusive. Therefore, the primary purpose of this systematic review and meta-analysis was to determine the effect of aerobic endurance training on daytime and night-time BP in healthy adults. A systematic literature search was conducted using PubMed and Cochrane Controlled Clinical trial registry from their inception to May 2012. Randomized controlled trials of at least 4 weeks investigating the effects of aerobic endurance training on ambulatory BP in healthy adults were included. Inverse weighted random effects models were used for analyses, with data reported as weighted means and 95% confidence limits. We included 15 randomized controlled trials, involving 17 study groups and 633 participants (394 exercise participants and 239 control participants). Overall, endurance training induced a significant reduction in daytime SBP [-3.2 mmHg, 95% confidence interval (CI), -5.0 to-1.3] and daytime DBP (-2.7 mmHg, 95% CI, -3.9 to -1.5). No effect was observed on night-time BP. The findings from this meta-analysis suggest that aerobic endurance exercise significantly decreases daytime, but not night-time, ambulatory BP.

Corona, G., G. Rastrelli, et al. (2013). "Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis." Eur J Endocrinol.

Objective. Few randomized clinical studies have evaluated the impact of diet and physical activity on testosterone (T) levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally showed an increase in T levels. The aim of the present study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels.Design. Meta-analysisMethods. An extensive Medline search was performed including the following words "testosterone", "diet", "weight loss" and "bariatric surgery" and "males". The search was restricted to data from January 1, 1969 up to August 31, 2012.Results. Out of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or of bariatric surgery, whereas 2 compared diet and bariatric surgery. Overall both low calorie diet and bariatric surgery are associated with a significant (p<0.0001) increase plasma sex hormone binding globulin bound and unbound T levels (TT), bariatric surgery being more effective in comparison with low calorie diet (TT increase = 8.73[6.51-10.95] vs 2.87[1.68-4.07] for bariatric surgery and low calorie diet, respectively; both p<0.0001 vs baseline). Androgen rise is greater in those patients that lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with and decrease in estradiol and increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50+/-0.98; p=0.029).Conclusions. Present data show that weight loss is associated with an increase of both bound and unbound T levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.

Costopoulos, C., D. A. Gorog, et al. (2013). "Use of thrombectomy devices in primary percutaneous coronary intervention: A systematic review and meta-analysis." Int J Cardiol 163(3): 229-41.

AIMS: Primary percutaneous coronary intervention (PPCI) has become the treatment of choice in patients with ST-elevation myocardial infarction (STEMI) over the recent years. A number of studies have demonstrated a morbidity and mortality benefit over thrombolysis, which has been attributed to better coronary perfusion in patients undergoing PPCI. However although PPCI usually achieves normal flow in the affected epicardial vessel, myocardial reperfusion is not fully restored in a significant percentage of patients. This is commonly the result of distal thrombus embolization with subsequent impairment of myocardial microcirculation. Recognition of this has led to the development of a number of devices with different mechanisms of action that aim to reduce such distal embolization and therefore improve end myocardial perfusion. Recent studies indeed demonstrate that the use of such devices offer additional clinical advantage in patients undergoing PPCI compared to the current practice. This report focuses on thrombectomy devices and reviews the evidence that advocates their routine use in PPCI patients. METHODS AND RESULTS: We have performed a systematic review of currently available thrombectomy devices. We also performed a literature search, using the terms "thrombectomy" and "thrombus aspiration" in PubMed and EMBASE. Thrombectomy devices were divided in "manual" and "non-manual" groups. We performed a meta-analysis of the available randomized control trials that compared adjunctive thrombectomy in PPCI to standard PPCI. The use of manual thrombectomy devices is associated with significant improvements in ST-segment resolution (STR) (p<0.00001), Myocardial Blush Grade (MBG) 3 (p<0.00001), Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow (p=0.01) as well as clinical parameters (43% reduction in mortality, p=0.04) in patients undergoing PPCI. CONCLUSION: Current evidence advocates the routine use of manual thrombectomy devices in PPCI. Non-manual (mechanical) thrombectomy may have a role in selected PPCI patients with large caliber vessels and heavy thrombus burden although their routine use is not presently supported.

Coughlin, P. A., D. Jackson, et al. (2013). "Meta-analysis of prospective trials determining the short- and mid-term effect of elective open and endovascular repair of abdominal aortic aneurysms on quality of life." Br J Surg 100(4): 448-55.

BACKGROUND: Repair of an abdominal aortic aneurysm (AAA) is undertaken to prevent rupture. Intervention is by either open repair (OR) or a more minimally invasive endovascular repair (EVAR). Quality-of-life (QoL) analysis is an important health outcome and a number of single studies have assessed QoL following OR and EVAR. This was a meta-analysis of published studies to assess the effect of an intervention on QoL in patients with an AAA. METHODS: A systematic literature search was undertaken for studies prospectively reporting QoL analysis in patients with an AAA undergoing elective intervention. A multivariable meta-analysis model was developed in which the outcomes were mean changes in QoL scores over time, both for all AAA repairs (OR and EVAR) and comparing OR with EVAR. RESULTS: Data were collated from 16 studies (14 OR, 12 EVAR). The results suggested that treating an AAA had an effect on patient-reported QoL, evident from the statistically significant changes predominantly in domains assessing physical ability and pain. QoL was affected most within the first 3 months after any form of intervention, and was more pronounced following OR. Furthermore, a deterioration in the Physical Component Summary score following an AAA repair (either OR or EVAR) was evident at 12 months after intervention. CONCLUSION: Treating an AAA deleteriously affects patient-reported QoL over the first year following intervention. Copyright (c) 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Couturier, J., M. Kimber, et al. (2013). "Efficacy of family-based treatment for adolescents with eating disorders: a systematic review and meta-analysis." Int J Eat Disord 46(1): 3-11.

OBJECTIVE: To systematically review and quantitatively evaluate the efficacy of Family-Based Treatment (FBT) compared with individual treatment among adolescents with eating disorders. METHOD: The literature was reviewed using the MEDLINE search terms "family therapy AND Anorexia Nervosa," and "family therapy AND Bulimia Nervosa". This produced 12 randomized controlled trials involving adolescents with eating disorders and family therapy which were reviewed carefully for several inclusion criteria including: allocation concealment, intent-to-treat analysis, assessor blinding, behavioral family therapy compared with an individual therapy, and adolescent age group. References from these articles were searched. Only three studies met these strict inclusion criteria for meta-analysis. A random effects model and odds ratio was used for meta-analysis, looking at "remission" as the outcome of choice. RESULTS: When combined in a meta-analysis, end of treatment data indicated that FBT was not significantly different from individual treatment (z = 1.62, p = 0.11). However, when follow-up data from 6 to 12 months were analyzed, FBT was superior to individual treatment (z = 2.94, p < 0.003), and heterogeneity was not significant (p = 0.59). DISCUSSION: Although FBT does not appear to be superior to individual treatment at end of treatment, there appear to be significant benefits at 6-12 month follow-up for adolescents suffering from eating disorders.

Covolo, L., T. Pollicino, et al. (2013). "Occult hepatitis B virus and the risk for chronic liver disease: A meta-analysis." Dig Liver Dis 45(3): 238-44.

BACKGROUND: The role of occult hepatitis B virus infection as a cause of liver disease is still debated although many studies found a higher prevalence of this condition in subjects than those without liver disease compared. A recent meta-analysis showed an increased risk of hepatocellular carcinoma for occult hepatitis B virus infection. AIMS: We carried out a meta-analysis of observational studies to summarize the existing evidence and assess quantitatively the association between occult hepatitis B virus infection and chronic liver disease. METHODS: We searched the available literature on this issue published up to May 2012 using PubMed and EMBASE. All articles that provided enough information to estimate the chronic liver disease risk associated with occult hepatitis B virus infection were selected. Fourteen studies were retrieved. RESULTS: A total of 1503 subjects with (cases) and 2052 without chronic liver disease (controls) were included. The summary odds ratio for chronic liver disease from all studies was 8.9 (95% confidence interval: 4.1-19.5). The meta-analysis restricted to 7 studies with more precise effect estimate (wt%>8%) provided a lower odds ratio estimate (odds ratio=3.9; 95% confidence interval: 1.7-9.0). CONCLUSIONS: These findings suggest a relevant association between occult hepatitis B virus infection and chronic liver disease, confirming the hypothesis that hepatitis B virus may play a pathogenic role even in the "occult" status.

Craig, D., S. Rice, et al. (2013). "Retigabine for the adjunctive treatment of adults with partial-onset seizures in epilepsy with and without secondary generalization : a NICE single technology appraisal." Pharmacoeconomics 31(2): 101-10.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of retigabine (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of adults with partial-onset seizures in epilepsy, with and without secondary generalization, as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination was commissioned to act as the Evidence Review Group (ERG). The ERG undertakes a critical review of the clinical and cost-effectiveness evidence of the technology based upon the manufacturer's submission to NICE. The ERG also independently searches for relevant evidence and evaluates modifications to the manufacturer's decision-analytic model. This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The clinical effectiveness data were derived from three placebo-controlled randomized controlled trials (RCTs). A meta-analysis pooling across all doses of retigabine found beneficial effects of retigabine in terms of responder rate (odds ratio [OR] 2.79; 95 % CI 2.08, 3.76) and rate of seizure freedom (OR 2.54; 95 % CI 0.92, 6.98) [both double-blind phase analyses]. When compared in a network meta-analysis with the selected comparator antiepileptic drugs (AEDs) [eslicarbazepine acetate, lacosamide, pregabalin, tiagabine and zonisamide], retigabine offered broadly similar efficacy in terms of responder rate and freedom from seizure. The de novo decision-analytic model presented within the submission evaluated the cost effectiveness of retigabine compared with these AEDs and no treatment (i.e. maintenance therapy). After numerous additional analyses, the ERG considered the use of retigabine to be not cost effective for NICE at thresholds below pound43,000 if no treatment was considered a relevant comparator. The NICE Appraisal Committee decided that an appropriate comparator was an active treatment. The Committee recommended that retigabine is offered as an option for the adjunctive treatment of partial-onset seizures with or without secondary generalization in adults aged 18 years and older with epilepsy, only when previous treatment with carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate and topiramate has not provided an adequate response, or has not been tolerated.

Cramer, H., R. Lauche, et al. (2013). "Yoga for schizophrenia: a systematic review and meta-analysis." BMC Psychiatry 13(1): 32.

ABSTRACT: BACKGROUND: The aim of this review was to systematically review and meta-analyze the effects of yoga on symptoms of schizophrenia, quality of life, function, and hospitalization in patients with schizophrenia. METHODS: MEDLINE/Pubmed, Scopus, the Cochrane Library, PsycInfo, and IndMED were screened through August 2012. Randomized controlled trials (RCTs) comparing yoga to usual care or non-pharmacological interventions were analyzed when they assessed symptoms or quality of life in patients with schizophrenia. Cognitive function, social function, hospitalization, and safety were defined as secondary outcomes. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. RESULTS: Five RCTs with a total of 337 patients were included; 2 RCTs had low risk of bias. Two RCTs compared yoga to usual care; 1 RCT compared yoga to exercise; and 2 3-arm RCTs compared yoga to usual care and exercise. No evidence was found for short-term effects of yoga compared to usual care on positive symptoms (SMD = -0.58; 95% CI -1.52 to 0.37; P = 0.23), or negative symptoms (SMD = -0.59; 95% CI -1.87 to 0.69; P = 0.36). Moderate evidence was found for short-term effects on quality of life compared to usual care (SMD = 2.28; 95% CI 0.42 to 4.14; P = 0.02). These effects were only present in studies with high risk of bias. No evidence was found for short-term effects on social function (SMD = 1.20; 95% CI -0.78 to 3.18; P = 0.23). Comparing yoga to exercise, no evidence was found for short-term effects on positive symptoms (SMD = -0.35; 95% CI -0.75 to 0.05; P = 0.09), negative symptoms (SMD = -0.28; 95% CI -1.42 to 0.86; P = 0.63), quality of life (SMD = 0.17; 95% CI -0.27 to 0.61; P = 0.45), or social function (SMD = 0.20; 95% CI -0.27 to 0.67; P = 0.41). Only 1 RCT reported adverse events. CONCLUSIONS: This systematic review found only moderate evidence for short-term effects of yoga on quality of life. As these effects were not clearly distinguishable from bias and safety of the intervention was unclear, no recommendation can be made regarding yoga as a routine intervention for schizophrenia patients.

Crawford, F., C. Anandan, et al. (2013). "Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS)." BMC Med Res Methodol 13(1): 22.

ABSTRACT: BACKGROUND: Diabetes--related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.Review questions;1.What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?2.Can the data from each study be adjusted for a consistent set of adjustment factors?3.Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? METHODS: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. DISCUSSION: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines.

Criaud, M. and P. Boulinguez (2013). "Have we been asking the right questions when assessing response inhibition in go/no-go tasks with fMRI? A meta-analysis and critical review." Neurosci Biobehav Rev 37(1): 11-23.

The popular go/no-go paradigm is supposed to ensure a reliable probing of response inhibition mechanisms. Functional magnetic resonance imaging (fMRI) studies have repeatedly found a large number of structures, usually including a right lateralized parieto-frontal network and the pre-supplementary motor area (pre-SMA). However, it is unlikely that all these regions are directly related to the mechanism that actively suppresses the motor command. Since most go/no-go designs involve complex stimulus identification/detection processes, these activations may rather reflect the engagement of different cognitive processes that are intrinsically related and quite difficult to disentangle. The current critical review is based on repeated meta-analyses of 30 go/no-go fMRI experiments using the Activation Likelihood Estimate method to contrast studies using simple vs. complex stimuli. The results show that most of the activity typically elicited by no-go signals, including pre-SMA hemodynamic response, is actually driven by the engagement of high attentional or working memory resources, not by inhibitory processes per se. Implications for current methods and theories of inhibitory control are discussed, and new lines of inquiry are proposed.

Crist, R. C., L. M. Ambrose-Lanci, et al. (2013). "Case-control association analysis of polymorphisms in the delta-opioid receptor, OPRD1, with cocaine and opioid addicted populations." Drug Alcohol Depend 127(1-3): 122-8.

BACKGROUND: Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The mu-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the delta-opioid receptor (DOR). METHODS: The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations. RESULTS: The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53 x 10(-5); n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 x 10(-7)) (p-values non-FDR corrected). CONCLUSION: The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.

Critchley, J. A., F. Young, et al. (2013). "Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis." Lancet Infect Dis 13(3): 223-37.

BACKGROUND: The effects of corticosteroids are systemic, but their benefits in tuberculosis are thought to be organ specific, with clinicians using them routinely to treat some forms of tuberculosis (such as meningitis), but not others. We aimed to assess the effects of steroids on mortality attributable to all forms of tuberculosis across organ systems. METHODS: We did a systematic review and meta-analysis to estimate the efficacy of steroids for the prevention of mortality in all forms of tuberculosis, and to quantify heterogeneity in this outcome between affected organ systems. We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Central Register of Controlled Trials, Medline, Embase, and Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS) for studies published up to Sept 6, 2012, and checked reference lists of included studies and relevant reviews. We included all trials in people with tuberculosis in any organ system, with tuberculosis defined clinically or microbiologically. There were no restrictions by age, comorbidity, publication language, or type, dose, or duration of steroid treatment. We used the Mantel-Haenszel method to summarise mortality across trials. FINDINGS: We identified 41 eligible trials, 18 of which assessed pulmonary tuberculosis. 20 of the 41 trials (including 13 of those for pulmonary tuberculosis) were done before the introduction of modern rifampicin-containing antituberculosis chemotherapy. Meta-analysis stratified by affected organ systems identified no heterogeneity; steroids reduced mortality by 17% (risk ratio [RR] 0.83, 95% CI 0.74-0.92; I(2) 0%), consistent across all organ groups. In a sensitivity analysis that only included trials that used rifampicin-containing regimens, the results were similar (RR 0.85, 95% CI 0.74-0.98; I(2) 21%). A sensitivity analysis in pulmonary tuberculosis that excluded trials with high potential risks of bias suggested a slight benefit, but the point estimate was closer to no effect and the difference was not significant (RR 0.93, 95% CI 0.60-1.44). INTERPRETATION: Steroids could be effective in reducing mortality for all forms of tuberculosis, including pulmonary tuberculosis. However, further evidence is needed since few recent trials have assessed the effectiveness of corticosteroids in patients with pulmonary tuberculosis. FUNDING: UK Department for International Development.

Cronin, M. J., S. Khan, et al. (2013). "The role of antibiotics in the treatment of acute rhinosinusitis in children: a systematic review." Arch Dis Child 98(4): 299-303.

OBJECTIVE: A systematic review of randomised controlled trials reporting the efficacy of antibiotics compared with placebo in the treatment of acute rhinosinusitis in children. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Register of Controlled Trials, Medline, Embase and references obtained from retrieved articles. RESULTS: Four studies fitted the selection criteria for inclusion. Risks for internal bias were thought to be small for each study, but external bias is potentially significant. The pooled OR for symptom improvement at 10-14 days favouring the use of antibiotics was 2.0 (95% CI 1.16 to 3.47; I2=14.8%). CONCLUSIONS: While the meta-analysis provides evidence to support the use of antibiotics for acute rhinosinusitis in children, it is the assessment of this review that such efficacy has not been adequately demonstrated. There remains a clear methodological challenge in the examination of this important clinical question; this challenge relates to difficulties in the application of appropriate diagnostic and inclusion criteria which are also consistent between studies.

Cuello-Garcia, C. A., G. Perez-Gaxiola, et al. (2013). "Treating BCG-induced disease in children." Cochrane Database Syst Rev 1: CD008300.

BACKGROUND: Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine to prevent tuberculosis, routinely administered at birth as part of the World Health Organization global expanded immunisation programme. Given intradermally, it can cause adverse reactions, including local, regional, distant and disseminated manifestations that may cause parental distress. Rarely, it can cause serious illness and even death. Among those patients with immunocompromised conditions, such as the human immunodeficiency virus (HIV) infection, the complication rate is even higher. OBJECTIVES: To assess the effects of different interventions for treating BCG-induced disease in children. SEARCH METHODS: The following databases were searched: the Cochrane Infectious Diseases Group Specialized Register and Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (The Cochrane Library 2012, Issue 4); MEDLINE (1966 to November 2012); EMBASE (1947 to November 2012); and LILACS (1980 to November 2012). The metaRegister of Controlled Trials (mRCT) and the WHO trials search portal. Conference proceedings for relevant abstracts and experts were also contacted to identify studies. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any medical or surgical treatment modality for BCG-induced disease in children. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated titles, applied inclusion criteria, and assessed the risk of bias of studies. The primary outcomes were the failure rate of therapies for all types of BCG vaccine-induced complications and the time to resolution of illness measured in months. The secondary outcomes were death from BCG vaccine-induced disease and the all-cause mortality. Risk ratios (RRs) were used as measure of effect for dichotomous outcomes and mean differences for continuous outcomes. MAIN RESULTS: Five RCTs analysing 341 children addressed the primary outcomes and were included. Four arms compared oral antibiotics to no intervention or placebo, one arm evaluated needle aspiration compared to no intervention, and another evaluated the use of locally instilled isoniazid versus oral erythromycin.Two small studies evaluated oral isoniazid; we are uncertain of whether this intervention has an effect on clinical failure (RR 1.48; 95% Confidence Interval (CI) 0.79 to 2.78; 54 participants, two studies, very low quality evidence). Similarly, for oral erythromycin, we are uncertain if there is an effect (clinical failure RR 1.03; 95% CI 0.70 to 1.53; 148 participants, three studies, very low quality evidence), and for oral isoniazid plus rifampicin (clinical failure, RR 1.20; 95% CI 0.51 to 2.83; 35 participants, one study, very low quality evidence).In patients with lymphadenitis abscess, needle aspiration may reduce clinically persistent BCG-induced disease at 6 to 9 months of follow-up (RR 0.13; 95% CI 0.03 to 0.55; 77 participants, one study, low quality evidence). In another study of patients with the same condition, aspiration plus local instillation of isoniazid reduces time to clinical cure compared to aspiration plus oral erythromycin (mean difference 1.49 months less; 95% CI 0.82 to 2.15 less; 27 participants, one study).No RCTs of HIV-infected infants with a BCG-induced disease evaluated the use of antibiotics or other therapies for reducing the rate of clinical failure or the time to clinical resolution. No data on mortality secondary to the interventions for treating BCG-induced disease were reported. AUTHORS' CONCLUSIONS: It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.

Cuello-Garcia, C. A., Y. M. Roldan-Benitez, et al. (2013). "Corticosteroids for neurocysticercosis: a systematic review and meta-analysis of randomized controlled trials." Int J Infect Dis.

BACKGROUND: Neurocysticercosis is an infection of the central nervous system by the larval stage of Taenia solium. It is a major cause of epileptic seizures in low- and middle-income countries. Corticosteroids are frequently used to reduce inflammation and perilesional edema. We aimed to evaluate their efficacy for reducing the rate of seizures and lesion persistence in imaging studies. METHODS: We searched randomized controlled trials in Medline, Central, EMBASE, LILACS, and the gray literature without language restrictions. We assessed eligibility, extracted data, and assessed the risk of bias in the included studies. The main outcomes included seizure recurrence and lesion persistence on imaging studies at 6-12 months of follow-up. Risk ratios (RR) were used for evaluating the main outcomes. RESULTS: Thirteen studies involving 1373 participants were included. The quality of the evidence was deemed low to very low. Corticosteroids alone versus placebo/no drug (five trials) reduced the rate of seizure recurrence at 6-12 months (RR 0.46, 95% confidence interval (CI) 0.27-0.77; 426 participants) and the persistence of lesions in imaging studies (RR 0.63, 95% CI 0.43-0.92; 417 participants). No differences were noted in other comparisons, including the use of corticosteroids and albendazole combined. Corticosteroids plus albendazole increased the risk of abdominal pain, rash, and headaches (odds ratio 8.73, 95% CI 2.09-36.5; 116 participants, one trial). CONCLUSIONS: Although the evidence suggest corticosteroids can reduce the rate of seizure recurrence and speed up resolution of lesions at 6-12 months of follow-up, there remains uncertainty on the effect estimate due to a high risk of methodological and publication bias. More adequately performed randomized trials that evaluate the use of anthelmintics, corticosteroids, and both combined against placebo are needed.

Cui, D., G. Huang, et al. (2013). "Efficacy and safety of interferon-gamma-targeted therapy in Crohn's disease: A systematic review and meta-analysis of randomized controlled trials." Clin Res Hepatol Gastroenterol.

AIMS: To evaluate the efficacy and safety of interferon-gamma-targeted therapy in Crohn's disease (CD). METHODS: Keyword and MeSH searches of MEDLINE/PubMed, EMBASE, the Cochrane Database, Science Citation Index and the Chinese Biomedical Database, from the inception of each database to March 2012, were used to identify all available randomized controlled trials. Summary estimates of treatment effects and safety were produced with Review Manager, using relative risks (RR) of clinical response, clinical remission and adverse events rates. RESULTS: Only three randomized controlled trials comparing anti-interferon-gamma therapy with placebo were qualified for the meta-analysis according to inclusion criteria. There were significant differences in clinical remission rates between groups (at week 6: RR=2.01, 95% confidence interval [CI]: 1.18-3.45; at week 8: RR=1.98, 95% CI: 1.17-3.33). There was also a significant difference in clinical response rates at week 8 (RR=1.60, 95% CI: 1.12-2.27). However, there was no statistically significant difference between anti-interferon-gamma therapy and placebo on adverse events rates (RR=0.98, 95% CI: 0.79-1.20). CONCLUSIONS: Anti-interferon-gamma therapy is safe and effective for treating active CD despite slow onset of action.

Cuijpers, P., D. P. de Beurs, et al. (2013). "The effects of psychotherapy for adult depression on suicidality and hopelessness: a systematic review and meta-analysis." J Affect Disord 144(3): 183-90.

BACKGROUND: Although treatment guidelines suggest that suicidal patients with depression should be treated for depression with psychotherapy, it is not clear whether these psychological treatments actually reduce suicidal ideation or suicide risk. METHODS: We conducted a systematic review and meta-analysis of studies on psychotherapy for depression in which outcomes on suicidality were reported. We also focused on outcomes on hopelessness because this is strongly associated with suicidal behavior in depression. RESULTS: Thirteen studies (with 616 patients) were included, three of which examined the effects of psychotherapy for depression on suicidal ideation and suicide risk, and eleven on hopelessness. No studies were found with suicide attempts or completed suicides as the outcome variables. The effects on suicidal ideation and suicide risk were small (g=0.12; 95% CI: -0.20-0.44) and not statistically significant. A power calculation showed that these studies only had sufficient power to find an effect size of g=0.47. The effects on hopelessness were large (g=1.10; 95% CI: 0.72-1.48) and significant, although heterogeneity was very high. Furthermore, significant publication bias was found. After adjustment of publication bias the effect size was reduced to g=0.60. DISCUSSION: At this point, there is insufficient evidence for the assumption that suicidality in depressed patients can be reduced with psychotherapy for depression. Although psychotherapy of depression may have small positive effects on suicidality, available data suggest that psychotherapy for depression cannot be considered to be a sufficient treatment. The effects on hopelessness are probably higher.

Cuijpers, P., N. Vogelzangs, et al. (2013). "Differential mortality rates in major and subthreshold depression: meta-analysis of studies that measured both." Br J Psychiatry 202(1): 22-7.

BACKGROUND: Although the association between depression and excess mortality has been well established, it is not clear whether this is greater in major depression than in subthreshold depression. AIMS: To compare excess mortality in major depression with that in subthreshold depression. METHOD: We searched bibliographic databases and included prospective studies in which both major and subthreshold depression were examined at baseline and mortality was measured at follow-up. RESULTS: A total of 22 studies were included. People with major depression had a somewhat increased chance of dying earlier than people with subthreshold depression but this difference was not significant, although there was a trend (relative risk 1.13, 95% CI 0.98-1.30, P = 0.1). The population attributable fraction was 7% for major depression and an additional 7% for subthreshold depression. CONCLUSIONS: Although excess mortality may be somewhat higher in major than in subthreshold depression, the difference is small and the overall impact on excess mortality is comparable.

Cumberworth, A., N. T. Mabvuure, et al. (2013). "Is home monitoring of international normalised ratio safer than clinic-based monitoring?" Interact Cardiovasc Thorac Surg 16(2): 198-201.

A best evidence topic was written according to a structured protocol, to answer the question: 'In patients taking warfarin, is home self-monitoring of international normalized ratio (INR) safer than clinic-based testing in reducing bleeding, thrombotic events and death?' Altogether, 268 papers were found using the reported search. Five papers represented the highest level of evidence to answer the clinical question (four systematic reviews with meta-analysis and one meta-analysis). The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The principal outcomes of interest were death, major haemorrhage, major thromboembolism, and time (or percentage time) spent within the therapeutic range, compared between self-monitoring/self-management and conventional management. Self-monitoring/self-management was associated with a significantly reduced risk of all-cause mortality of 26-42%. All meta-analyses reported on major thromboembolism, finding significant reductions in risk of ~50%. One meta-analysis found a 35% reduction in the risk of major haemorrhage, with the other four studies finding no significant difference. Only one study found self-monitoring/self-management to be associated with a significantly greater proportion of time within range, with another finding no significant difference in either the percentage of therapeutic results or in the time within range. The remaining two could not combine data for meta-analysis owing to methodological heterogeneity. We conclude that self-monitoring/self-management appears to be safer than conventional management. It is associated with consistently lower rates of thromboembolism and may also be associated with reduced risk of bleeding and death. This supports the updated guidance from the American College of Chest Physicians, recommending self-management of INR for patients who are both competent and motivated.

Cuming, T., A. Ghanbari, et al. (2013). "Re: Four-Liter Split-Dose Polyethylene Glycol Is Superior to Other Bowel Preparations on the Basis of Systematic Review and Meta-analysis." Clin Gastroenterol Hepatol 11(3): 322.

da Costa, B. R., R. Hilfiker, et al. (2013). "PEDro's bias: summary quality scores should not be used in meta-analysis." J Clin Epidemiol 66(1): 75-7.

Dack, C., J. Ross, et al. (2013). "A review and meta-analysis of the patient factors associated with psychiatric in-patient aggression." Acta Psychiatr Scand 127(4): 255-268.

OBJECTIVE: To combine the results of earlier comparison studies of in-patient aggression to quantitatively assess the strength of the association between patient factors and i) aggressive behaviour,ii) repetitive aggressive behaviour. METHOD: A systematic review and meta-analysis of empirical articles and reports of comparison studies of aggression and non-aggression within adult psychiatric in-patient settings. RESULTS: Factors that were significantly associated with in-patient aggression included being younger, male, involuntary admissions, not being married, a diagnosis of schizophrenia, a greater number of previous admissions, a history of violence, a history of self-destructive behaviour and a history of substance abuse. The only factors associated with repeated in-patient aggression were not being male, a history of violence and a history of substance abuse. CONCLUSION: By comparing aggressive with non-aggressive patients, important differences between the two populations may be highlighted. These differences may help staff improve predictions of which patients might become aggressive and enable steps to be taken to reduce an aggressive incident occurring using actuarial judgements. However, the associations found between these actuarial factors and aggression were small. It is therefore important for staff to consider dynamic factors such as a patient's current state and the context to reduce in-patient aggression.

Dadoun, S., N. Zeboulon-Ktorza, et al. (2013). "Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-analysis." Joint Bone Spine 80(1): 29-33.

OBJECTIVE: Mortality rates in patients with rheumatoid arthritis (RA) have been reported to be higher than for the general population. Fortunately, efficient therapies have reduced disease activity and may be able to diminish the excess mortality risk. This study was designed to investigate RA mortality over the last 50 years by systematic review of the literature and meta-analysis. METHODS: Data to January 2010 in the Medline, Cochrane and Embase databases were searched with the keywords "rheumatoid arthritis", "epidemiologic methods" and "mortality". Inclusion criteria were (i) longitudinal study, (ii) early RA patients, (iii) number of deaths and mean patient follow-up. Incidence mortality rates (IMR) were calculated and standardized mortality rates (SMR) were extracted when available. A meta-analysis by periods of inclusion and a Poisson regression were used to model IMR. Available SMR were computed as a meta-analysis. RESULTS: A total of 11 longitudinal studies starting from 1955 to 1995, representing 51,819 patients, met the inclusion criteria. Mean IMR was 2.7/100 person-years of follow-up (95% confidence interval [CI]: 2.2, 3.3) and ranged from 1.0 to 5.2/100 person-years. A decreasing IMR was found in the meta-analyses. Poisson regression analysis indicated a decrease in IMR of 2.3% per year (95%CI: 2.1; 2.6). SMR was available in 8 studies: the meta-SMR was 1.47 (95%CI: 1.19; 1.83) and no decrease was seen over time in the meta-regression. CONCLUSION: Mortality has decreased among RA patients over the past decades but remained higher than in the general population as assessed by the IMR and the SMR over time.

Dadvand, P., J. Parker, et al. (2013). "Maternal exposure to particulate air pollution and term birth weight: a multi-country evaluation of effect and heterogeneity." Environ Health Perspect 121(3): 267-373.

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent.Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association.Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter </= 10 and 2.5 microm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates.Results: In random-effects meta-analyses, term LBW was positively associated with a 10-mug/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-mug/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (-8.9 g; 95% CI: -13.2, -4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations.Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.

Dai, B., T. Liu, et al. (2013). "The polymorphism for endothelial nitric oxide synthase gene, the level of nitric oxide and the risk for pre-eclampsia: A meta-analysis." Gene.

Endothelial NO, which is synthesized by endothelial nitric oxide synthase (eNOS), has been reported to be related with the occurrence of pre-eclampsia (PE). However, the polymorphisms of eNOS (-786T>C, 4b/a and G894T), the level of nitric oxide and the risk of PE remain unclear. Thus we performed this meta-analysis to determine the associations between them in order to predict the risk for PE and interference with PE development in the early period of antenatal care. All studies investigating the associations between PE risk and polymorphisms of eNOS, or PE risk and serum concentration of NO were reviewed. Finally, 29 studies were included, involving 11 for -786T>C, 11for 4b/a, and 22 for G894T polymorphisms and PE risk. In the overall analysis, -786T>C polymorphism was found to be related with increased PE risk in the dominant model (OR=1.17, 95% CI=1.02-1.35). a allele for 4b/a suffers the high risk of PE (OR=1.46, 95% CI=1.01-2.10). In the subgroup analysis, significantly increased risk was detected among Europeans for -786T>C polymorphism (OR=1.40, 95%CI=1.14-1.73).However, no significant association was detected for G894T polymorphism in the overall and subgroup analysis. The comprehensive evaluation of 9 available studies indicated that serum NO level was significantly decreased in case group (SMD=-0.96umol/mL, 95%CI=-1.80, -0.12umol/mL).Hence, we concluded that eNOS gene -786T>C and 4b/a except for G894T polymorphisms were contributed significantly to PE risk, especially for Europeans, and a low NO concentration in serum increased the risk for PE.

Dai, C., Z. Lu, et al. (2013). "Bilateral Internal Mammary Artery Grafting and Risk of Sternal Wound Infection: Evidence From Observational Studies." Ann Thorac Surg.

BACKGROUND: The advantageous survival outcome of bilateral internal mammary artery grafting (BIMA) has been well established. However, this meta-analysis aims to make clear whether BIMA grafting increases the risk of sternal wound infection (SWI) when compared with single internal mammary artery grafting (SIMA). METHODS: A literature search was performed in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The observational studies reporting a comparison between SIMA and BIMA were included. The outcome of interest was the risk of SWI. Literature search, data extraction, and quality assessment were performed. Sensitivity and publication bias were also assessed in this research. RESULTS: We identified 4,701 titles and included 32 studies finally. The meta-analysis showed that the risk of SWI in the BIMA group was higher (relative risk [RR] 0.62, 95% confidence interval [CI] 0.55 to 0.71) than that in the SIMA group. Moreover, BIMA grafting was also associated with a higher risk of SWI in diabetic patients (RR 0.65, 95% CI 0.52 to 0.81) as well as elderly patients (RR 0.45, 95% CI 0.33 to 0.62). When skeletonization technique was adopted, the risk of SWI in BIMA patients was just a little higher than that in SIMA patients, but the difference did not reach statistical significance (RR 0.84, 95% CI 0.54 to 1.31). CONCLUSIONS: The BIMA grafting increases the risk of SWI when compared with SIMA grafting. This adverse effect further extends to diabetic and elderly patients. As regarding the method of procurement, skeletonized BIMA is safe and effective, thus it should be the procedure recommended.

Dai, G., Z. Guo, et al. (2013). "Association of 8q24 rs13281615A > G polymorphism with breast cancer risk: evidence from 40,762 cases and 50,380 controls." Mol Biol Rep.

The association between a single nucleotide polymorphism rs13281615A > G located in the 8q24 and breast cancer risk is still controversial and ambiguous. Hence, we performed a more convincing and precise estimation of the relationship between 8q24 and breast cancer by meta-analyzing the currently available evidence from literature. PubMed, Ovid, Medline, and Web of Science databases were searched. A total of 10 publications containing 11 studies including 40,762 cases and 50,380 controls were identified. Crude odds ratio with 95 % confidence interval was used to assess the strength of association. We observed that the 8q24 rs13281615A > G polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta analysis. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for all genetic models. For mixed ethnicities, significantly increased risks were found for all genetic models except for the allele contrast model. However, no significantly increased risk was found among Africans for all genetic models. Interestingly, when stratified by BRCA1 mutation carriers status, significantly decreased breast cancer risk was found for allele contrast model. But significantly increased breast cancer risk was found in the BRCA2 mutation carriers for all genetic models except for the recessive model. There was no evidence for significant association between 8q24 rs13281615A > G polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparable models. In conclusion, this meta-analysis suggests that the 8q24 rs13281615A > G polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.

Dai, J., Y. Chai, et al. (2013). "Meta-analysis comparing locking plate fixation with hemiarthroplasty for complex proximal humeral fractures." Eur J Orthop Surg Traumatol.

BACKGROUND: There remains no consensus on the surgical treatment of complex proximal humeral fractures. In this meta-analysis, we pool available trials to compare the clinical outcomes of locking plate fixation and hemiarthroplasty for this injury. METHODS: A literature search between January 1990 and May 2012 in the main medical search engines (Pubmed, Medline, Embase search, and the Cochrane library) was included. We selected available trials that compared locking plate fixation and hemiarthroplasty in patients with complex proximal humeral fractures and that reported on functional outcomes, revisions, and method-related complications. The quality of the studies was assessed, and meta-analyses were performed with the Cochrane Collaboration's REVMAN 5.0 software. RESULTS: A total of 567 patients from 9 trials were included in this meta-analysis (302 fractures treated with locking plate and 265 with hemiarthroplasty). In this comparison, we found that patients with locking plate fixation had better Constant-Murley score than with hemiarthroplasty, and hemiarthroplasty could reduce the rate of revisions and the method-related complications significantly. CONCLUSIONS: Compared with hemiarthroplasty, patients with locking plate fixation could obtain more favorable functional outcomes, but technical detail was critical to minimize the risk of implant failure, avascular necrosis, and re-operation. As the possible significant bias and inconclusive evidence arising from the included trials, further randomized trials and observational studies should be recommended to support these finding.

Dai, Y., Y. Feng, et al. (2013). "Erratum to: Evaluation of interferon-gamma release assays for the diagnosis of tuberculosis: an updated meta-analysis." Eur J Clin Microbiol Infect Dis.

Dai, Z. W., C. Leon, et al. (2013). "Metabolic profiling reveals coordinated switches in primary carbohydrate metabolism in grape berry (Vitis vinifera L.), a non-climacteric fleshy fruit." J Exp Bot.

Changes in carbohydrate metabolism during grape berry development play a central role in shaping the final composition of the fruit. The present work aimed to identify metabolic switches during grape development and to provide insights into the timing of developmental regulation of carbohydrate metabolism. Metabolites from central carbon metabolism were measured using high-pressure anion-exchange chromatography coupled to tandem mass spectrometry and enzymatic assays during the development of grape berries from either field-grown vines or fruiting cuttings grown in the greenhouse. Principal component analysis readily discriminated the various stages of berry development, with similar trajectories for field-grown and greenhouse samples. This showed that each stage of fruit development had a characteristic metabolic profile and provided compelling evidence that the fruit-bearing cuttings are a useful model system to investigate regulation of central carbon metabolism in grape berry. The metabolites measured showed tight coordination within their respective pathways, clustering into sugars and sugar-phosphate metabolism, glycolysis, and the tricarboxylic acid cycle. In addition, there was a pronounced shift in metabolism around veraison, characterized by rapidly increasing sugar levels and decreasing organic acids. In contrast, glycolytic intermediates and sugar phosphates declined before veraison but remained fairly stable post-veraison. In summary, these detailed and comprehensive metabolite analyses revealed the timing of important switches in primary carbohydrate metabolism, which could be related to transcriptional and developmental changes within the berry to achieve an integrated understanding of grape berry development. The results are discussed in a meta-analysis comparing metabolic changes in climacteric versus non-climacteric fleshy fruits.

Dale, M. and S. M. Benson (2013). "Energy Balance of the Global Photovoltaic (PV) Industry - Is the PV Industry a Net Electricity Producer?" Environ Sci Technol.

A combination of declining costs and policy measures motivated by greenhouse gas (GHG) emissions reduction and energy security have driven rapid growth in the global installed capacity of solar photovoltaics (PV). This paper develops a number of unique data sets, namely the following: calculation of distribution of global capacity factor for PV deployment; meta-analysis of energy consumption in PV system manufacture and deployment; and documentation of reduction in energetic costs of PV system production. These data are used as input into a new net energy analysis of the global PV industry, as opposed to device level analysis. In addition, the paper introduces a new concept: a model tracking energetic costs of manufacturing and installing PV systems, including balance of system (BOS) components. The model is used to forecast electrical energy requirements to scale up the PV industry and determine the electricity balance of the global PV industry to 2020. Results suggest that the industry was a net consumer of electricity as recently as 2010. However, there is a >50% that in 2012 the PV industry is a net electricity provider and will "pay back" the electrical energy required for its early growth before 2020. Further reducing energetic costs of PV deployment will enable more rapid growth of the PV industry. There is also great potential to increase the capacity factor of PV deployment. These conclusions have a number of implications for R&D and deployment, including the following: monitoring of the energy embodied within PV systems; designing more efficient and durable systems; and deploying PV systems in locations that will achieve high capacity factors.

Daneman, N., S. Sarwar, et al. (2013). "Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis." Lancet Infect Dis.

BACKGROUND: Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) in intensive care units (ICUs). These interventions have not been widely implemented because of concerns that their use could lead to the development of antimicrobial resistance in pathogens. We aimed to assess the effect of SDD and SOD on antimicrobial resistance rates in patients in ICUs. METHODS: We did a systematic review of the effect of SDD and SOD on the rates of colonisation or infection with antimicrobial-resistant pathogens in patients who were critically ill. We searched for studies using Medline, Embase, and Cochrane databases, with no limits by language, date of publication, study design, or study quality. We included all studies of selective decontamination that involved prophylactic application of topical non-absorbable antimicrobials to the stomach or oropharynx of patients in ICUs, with or without additional systemic antimicrobials. We excluded studies of interventions that used only antiseptic or biocide agents such as chlorhexidine, unless antimicrobials were also included in the regimen. We used the Mantel-Haenszel model with random effects to calculate pooled odds ratios. FINDINGS: We analysed 64 unique studies of SDD and SOD in ICUs, of which 47 were randomised controlled trials and 35 included data for the detection of antimicrobial resistance. When comparing data for patients in intervention groups (those who received SDD or SOD) versus data for those in control groups (who received no intervention), we identified no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1.46, 95% CI 0.90-2.37) and vancomycin-resistant enterococci (0.63, 0.39-1.02). Among Gram-negative bacilli, we detected no difference in aminoglycoside-resistance (0.73, 0.51-1.05) or fluoroquinolone-resistance (0.52, 0.16-1.68), but we did detect a reduction in polymyxin-resistant Gram-negative bacilli (0.58, 0.46-0.72) and third-generation cephalosporin-resistant Gram-negative bacilli (0.33, 0.20-0.52) in recipients of selective decontamination compared with those who received no intervention. INTERPRETATION: We detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates. FUNDING: None.

D'Angiulli, A., M. Runge, et al. (2013). "Vividness of visual imagery and incidental recall of verbal cues, when phenomenological availability reflects long-term memory accessibility." Front Psychol 4: 1.

The relationship between vivid visual mental images and unexpected recall (incidental recall) was replicated, refined, and extended. In Experiment 1, participants were asked to generate mental images from imagery-evoking verbal cues (controlled on several verbal properties) and then, on a trial-by-trial basis, rate the vividness of their images; 30 min later, participants were surprised with a task requiring free recall of the cues. Higher vividness ratings predicted better incidental recall of the cues than individual differences (whose effect was modest). Distributional analysis of image latencies through ex-Gaussian modeling showed an inverse relation between vividness and latency. However, recall was unrelated to image latency. The follow-up Experiment 2 showed that the processes underlying trial-by-trial vividness ratings are unrelated to the Vividness of Visual Imagery Questionnaire (VVIQ), as further supported by a meta-analysis of a randomly selected sample of relevant literature. The present findings suggest that vividness may act as an index of availability of long-term sensory traces, playing a non-epiphenomenal role in facilitating the access of those memories.

Daniels, J. K., J. P. Lamke, et al. (2013). "White matter integrity and its relationship to ptsd and childhood trauma-a systematic review and meta-analysis." Depress Anxiety 30(3): 207-16.

Recent reviews and meta-analyses reported structural gray matter changes in patients suffering from adult-onset posttraumatic stress disorder (PTSD) and in subjects with and without PTSD who experienced childhood trauma. However, it remains unclear if such structural changes are also affecting the white matter. The aim of this systematic review is to provide a comprehensive overview of all empirical investigations measuring white matter integrity in populations affected by PTSD and/or childhood trauma. To this end, results from different methodological approaches were included. Twenty-five articles are reviewed of which 10 pertained to pediatric PTSD and the effects of childhood trauma measured during childhood, seven to the effects of childhood trauma measured during adulthood, and eight to adult-onset PTSD. Overall, reductions in white matter volume were reported more often than increases in these populations. However, the heterogeneity of the exact locations indicates only a weak overlap across published studies. In addition, a meta-analysis was carried out on seven whole-brain diffusion tensor imaging (DTI) studies in adults. Significant clusters of both increases and decreases were identified in various structures, most notably the cingulum and the superior longitudinal fasciculus. Future research directions are discussed.

Das, R., S. Cope, et al. (2013). "Economic Evaluation of Fulvestrant 500 mg Versus Generic Nonsteroidal Aromatase Inhibitors in Patients With Advanced Breast Cancer in the United Kingdom." Clin Ther.

OBJECTIVE: The goal of this study was to examine the cost-effectiveness of fulvestrant 500 mg for the treatment of first progression or recurrence of advanced breast cancer in postmenopausal patients compared with generic nonsteroidal aromatase inhibitors (anastrozole and letrozole) in the United Kingdom. METHODS: A cost-utility model based on a time-in-state approach was used. Clinical effectiveness estimates used in the model were derived from a network meta-analysis for overall survival and serious adverse events. Overall survival was extrapolated by using a Weibull distribution, and progression-free survival (PFS) estimates were derived from a simultaneous network meta-analysis and extrapolation of PFS curves by using the log-normal distribution. Data on resource use, costs, and utilities were based on various sources, including expert opinion and published data. To explore uncertainty, 1-way and probability sensitivity analyses were conducted. The study was conducted from the perspective of the UK National Health Service, and costs are reported in 2010/2011 British pounds. RESULTS: The base case incremental cost-effectiveness ratio (ICER) for fulvestrant 500 mg versus letrozole was pound34,528, with incremental costs of pound14,383 and an incremental quality-adjusted life-year (QALY) of 0.417. Extended dominance occurred for anastrozole because the ICER for anastrozole versus letrozole was higher than the ICER for fulvestrant 500 mg versus anastrozole. Based on the probability sensitivity analyses, the probability that fulvestrant 500 mg was the most cost-effective treatment option was 3%, 20%, and 53% at a willingness-to-pay threshold of pound20,000, pound30,000, and pound40,000 per QALY, respectively. According to the 1-way sensitivity analyses, the PFS estimates were the key drivers of the model results. CONCLUSIONS: Although fulvestrant 500 mg was found not to be a cost-effective option at a standard UK threshold of pound20,000 to pound30,000 per QALY, it may be relevant to apply a higher threshold due to the poor prognosis of patients with advanced breast cancer and the limited number of hormonal treatment options available for this stage of treatment. Certain subgroups may also benefit from fulvestrant as a treatment option; however, limited data are currently available to identify these subgroups.

Daselaar, S. M., W. Huijbers, et al. (2013). "Resting-state functional connectivity of ventral parietal regions associated with attention reorienting and episodic recollection." Front Hum Neurosci 7: 38.

In functional neuroimaging studies, ventral parietal cortex (VPC) is recruited by very different cognitive tasks. Explaining the contributions of VPC to these tasks has become a topic of intense study and lively debate. Perception studies frequently find VPC activations during tasks involving attention-reorienting, and memory studies frequently find them during tasks involving episodic recollection. According to the Attention to Memory (AtoM) model, both phenomena can be explained by the same VPC function: bottom-up attention. Yet, a recent functional MRI (fMRI) meta-analysis suggested that attention-reorienting activations are more frequent in anterior VPC, whereas recollection activations are more frequent in posterior VPC. Also, there is evidence that anterior and posterior VPC regions have different functional connectivity patterns. To investigate these issues, we conducted a resting-state functional connectivity analysis using as seeds the center-of-mass of attention-reorienting and recollection activations in the meta-analysis, which were located in the supramarginal gyrus (SMG, around the temporo-parietal junction-TPJ) and in the angular gyrus (AG), respectively. The SMG seed showed stronger connectivity with ventrolateral prefrontal cortex (VLPFC) and occipito-temporal cortex, whereas the AG seed showed stronger connectivity with the hippocampus and default network regions. To investigate whether these connectivity differences were graded or sharp, VLPFC and hippocampal connectivity was measured in VPC regions traversing through the SMG and AG seeds. The results showed a graded pattern: VLPFC connectivity gradually decreases from SMG to AG, whereas hippocampal connectivity gradually increases from SMG to AG. Importantly, both gradients showed an abrupt break when extended beyond VPC borders. This finding suggests that functional differences between SMG and AG are more subtle than previously thought. These connectivity differences can be explained by differences in the input and output to anterior and posterior VPC regions, without the need of postulating markedly different functions. These results are as consistent with integrative accounts of VPC function, such as the AtoM model, as they are with models that ascribe completely different functions to VPC regions.

Daugherty, A. and N. Raz (2013). "Age-related differences in iron content of subcortical nuclei observed in vivo: A meta-analysis." Neuroimage 70: 113-21.

Accumulation of non-heme iron in the brain has been proposed as a biomarker of the progressive neuroanatomical and cognitive declines in healthy adult aging. Postmortem studies indicate that iron content and lifespan differences therein are regionally specific, with a predilection for the basal ganglia. However, the reported in vivo estimates of adult age differences in iron content within subcortical nuclei are highly variable. We present a meta-analysis of 20 in vivo magnetic resonance imaging (MRI) studies that estimated iron content in the caudate nucleus, globus pallidus, putamen, red nucleus, and substantia nigra. The results of the analyses support a robust association between advanced age and high iron content in the substantia nigra and striatum, with a smaller effect noted in the globus pallidus. The magnitude of age differences in estimated iron content of the caudate nucleus and putamen partially depended on the method of estimation, but not on the type of design (continuous age vs. extreme age groups).

Davies, A., K. P. Singh, et al. (2013). "Treatment Outcomes of Treatment-Naive Hepatitis C Patients Co-Infected with HIV: A Systematic Review and Meta-Analysis of Observational Cohorts." PLoS One 8(2): e55373.

INTRODUCTION: Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor. METHODS: We conducted a systematic review and meta-analysis to assess HCV treatment outcomes in observational cohorts. Two databases (Medline and EMBASE) were searched using a compound search strategy for cohort studies reporting HCV treatment outcomes (as determined by a sustained virological response, SVR) in HIV-positive patients initiating HCV treatment for the first time. RESULTS: 40 studies were included for review, providing outcomes on 5339 patients from 17 countries. The pooled proportion of patients achieving SVR was 38%. Significantly poorer outcomes were observed for patients infected with HCV genotypes 1 or 4 (pooled SVR 24.5%), compared to genotypes 2 or 3 (pooled SVR 59.8%). The pooled proportion of patients who discontinued treatment due to drug toxicities (reported by 33 studies) was low, at 4.3% (3.3-5.3%). Defaulting from treatment, reported by 33 studies, was also low (5.1%, 3.5-6.6%), as was on-treatment mortality (35 studies, 0.1% (0-0.2%)). CONCLUSIONS: These results, reported under programmatic conditions, are comparable to those reported in randomised clinical trials, and show that although HCV treatment outcomes are generally poor in HIV co-infected patients, those infected with HCV genotypes 2 or 3 have outcomes comparable to HIV-negative patients.

Davis, A. P., C. G. Murphy, et al. (2013). "The Comparative Toxicogenomics Database: update 2013." Nucleic Acids Res 41(Database issue): D1104-14.

The Comparative Toxicogenomics Database (CTD; provides information about interactions between environmental chemicals and gene products and their relationships to diseases. Chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature are integrated to generate expanded networks and predict many novel associations between different data types. CTD now contains over 15 million toxicogenomic relationships. To navigate this sea of data, we added several new features, including DiseaseComps (which finds comparable diseases that share toxicogenomic profiles), statistical scoring for inferred gene-disease and pathway-chemical relationships, filtering options for several tools to refine user analysis and our new Gene Set Enricher (which provides biological annotations that are enriched for gene sets). To improve data visualization, we added a Cytoscape Web view to our ChemComps feature, included color-coded interactions and created a 'slim list' for our MEDIC disease vocabulary (allowing diseases to be grouped for meta-analysis, visualization and better data management). CTD continues to promote interoperability with external databases by providing content and cross-links to their sites. Together, this wealth of expanded chemical-gene-disease data, combined with novel ways to analyze and view content, continues to help users generate testable hypotheses about the molecular mechanisms of environmental diseases.

Davis, D., J. Gregson, et al. (2013). "Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies." Neuroepidemiology 40(1): 56-67.

BACKGROUND: Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. METHODS: Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. RESULTS: We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9-2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0-2.5; 2 studies; OR 1.3; 95% CI 0.9-1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6-1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. CONCLUSIONS: The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect.

Davis, J. L., A. Cattamanchi, et al. (2013). "Diagnostic accuracy of same-day microscopy versus standard microscopy for pulmonary tuberculosis: a systematic review and meta-analysis." Lancet Infect Dis 13(2): 147-54.

BACKGROUND: Sputum smear microscopy is the most widely available diagnostic test for pulmonary tuberculosis in countries with a high burden of the disease. Improving its accuracy is crucial to achievement of case-detection targets established by the Millennium Development Goals. Unfortunately, many patients are unable to submit all of the specimens needed for examination or to return for treatment because standard sputum collection and reporting requires several clinic visits. To inform policy recommendations by a WHO-convened Expert Group, we aimed to assess the accuracy of sputum smear examination with strategies for obtaining sputum on 1 day compared with strategies for obtaining sputum over 2 days. METHODS: We did a systematic review and meta-analysis of research articles comparing the accuracy of front-loaded or same-day microscopy and standard sputum smear microscopy for diagnosis of culture-confirmed pulmonary tuberculosis. We searched Medline, Embase, Biosis, and Web of Science for articles published between Jan 1, 2005, and Feb 14, 2012. Two investigators identified eligible articles and extracted data for individual study sites. We generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when four or more studies were available. FINDINGS: We identified eight relevant studies from five articles enrolling 7771 patients with suspected tuberculosis in low-income countries. Compared with the standard approach of examination of two smears with Ziehl-Neelsen light microscopy over 2 days, examination of two smears taken on the same day had much the same sensitivity (64% [95% CI 60 to 69] for standard microscopy vs 63% [58 to 68] for same-day microscopy) and specificity (98% [97 to 99] vs 98% [97 to 99]). We noted similar results for studies employing light-emitting diode fluorescence microscopy and for studies examining three smears, whether they were compared with two-smear strategies or with one another. INTERPRETATION: Same-day sputum smear microscopy is as accurate as standard smear microscopy. Data from tuberculosis programmes are needed to document the changes required in the health system to successfully implement the strategy and understand its effects. FUNDING: WHO and US National Institutes of Health.

de Brandao, M. L., M. V. Vettore, et al. (2013). "Peri-implant bone loss in cement- and screw-retained prostheses: Systematic review and meta-analysis." J Clin Periodontol 40(3): 287-95.

AIM: The aim of this systematic review and meta-analysis was to assess and compare peri-implant marginal bone loss in cement- and screw-retained prostheses. MATERIAL AND METHODS: Electronic database and manual searches were undertaken to identify trials, prospective or retrospective studies reporting on radiographic marginal bone loss around dental implants restored with cement- and/or screw-retained prostheses. Two reviewers independently conducted the article selection and data extraction. Random-effects models were used to obtain estimates of peri-implant marginal bone loss [mean, 95% confidence intervals (CI)]. RESULTS: Of the 1217 identified studies, nine finally met the inclusion criteria. Only two studies included both cement- and screw-retained prostheses, three assessed only screw-retained prostheses, and four evaluated only cement-retained prostheses. Pooled mean marginal bone loss was 0.53 mm (CI 95%, 0.31-0.76 mm) for cement-retained prostheses and 0.89 mm (CI 95%, 0.45-1.33 mm) for screw-retained prostheses. CONCLUSION: There is no evidence to support differences in the marginal bone loss through indirect comparison between cement and screw-retained restorations.

De Caluwe, L., Y. Van Nieuwenhove, et al. (2013). "Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer." Cochrane Database Syst Rev 2: CD006041.

BACKGROUND: Preoperative radiotherapy (RT) decreases local recurrence rate and improves survival in stage II and III rectal cancer patients. The combination of chemotherapy with RT has a sound radiobiological rationale, and phase II trials of combined chemoradiation (CRT) have shown promising activity in rectal cancer. OBJECTIVES: To compare preoperative RT with preoperative CRT in patients with resectable stage II and III rectal cancer. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials, Web of Science,, and Pubmed from 1975 until June 2012. A manual search was performed of Ann Surg, Arch Surg, Cancer, J Clin Oncol, Int J Radiat Oncol Biol Phys and the proceedings of ASTRO, ECCO and ASCO from 1990 until June 2012. SELECTION CRITERIA: Relevant studies randomized resectable stage II or III rectal cancer patients to at least one arm of preoperative RT alone or at least one arm of preoperative CRT. DATA COLLECTION AND ANALYSIS: Primary outcome parameters included overall survival (OS) at 5 years and local recurrence (LR) rate at 5 years. Secondary outcome parameters included disease free survival (DFS) at 5 years, metastasis rate, pathological complete response rate, clinical response rate, sphincter preservation rate, acute toxicity, postoperative mortality and morbidity, and anastomotic leak rate. Outcome parameters were summarized using the Odds Ratio (OR) and associated 95% confidence interval (CI) using the fixed effects model. MAIN RESULTS: Five trials were identified and included in the meta-analysis. From one of the included trials only preliminary data are reported. The addition of chemotherapy to preoperative RT significantly increased grade III and IV acute toxicity (OR 1.68-10, P = 0.002) and marginally affected postoperative overall morbidity (OR 0.67-1.00, P = 0.05) while no differences were observed in postoperative mortality or anastomotic leak rate. Compared to preoperative RT alone, preoperative CRT significantly increased the rate of complete pathological response (OR 2.12-5.84, P < 0.00001) although this did not translate into a higher sphincter preservation rate (OR 0.92-1.30, P = 0.32). The incidence of local recurrence at five years was significantly lower in the CRT group compared to RT alone (OR 0.39-0.72, P < 0.001). No statistically significant differences were observed in DFS (OR 0.92-1.34, P = 0.27) or OS (OR 0.79-1.14, P = 0.58) at five years. AUTHORS' CONCLUSIONS: Compared to preoperative RT alone, preoperative CRT enhances pathological response and improves local control in resectable stage II and III rectal cancer, but does not benefit disease free or overall survival. The effects of preoperative CRT on functional outcome and quality of life are incompletely understood and should be addressed in future trials.

de Goede, B., P. J. Klitsie, et al. (2013). "Meta-analysis of laparoscopic versus open cholecystectomy for patients with liver cirrhosis and symptomatic cholecystolithiasis." Br J Surg 100(2): 209-16.

BACKGROUND: Open cholecystectomy (OC) is often preferred over laparoscopic cholecystectomy (LC) in patients with liver cirrhosis and portal hypertension, but evidence is lacking to support this practice. This meta-analysis aimed to clarify which surgical technique is preferable for symptomatic cholecystolithiasis in patients with liver cirrhosis. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and October 2011 were identified from MEDLINE, Embase and the Cochrane Library. Randomized clinical trials (RCTs) comparing outcomes of OC versus LC for cholecystolithiasis in patients with liver cirrhosis were included. The quality of the RCTs was assessed using the Jadad criteria. RESULTS: Following review of 1422 papers by title and abstract, a meta-analysis was conducted of four RCTs comprising 234 surgical patients. They provided evidence of at least level 2b on the Oxford Level of Evidence Scale, but scored poorly according to the Jadad criteria. Some 97.0 per cent of the patients had Child-Turcotte-Pugh (CTP) grade A or B liver cirrhosis. In all, 96.6 per cent underwent elective surgery. No postoperative deaths were reported. LC was associated with fewer postoperative complications (risk ratio 0.52, 95 per cent confidence interval (c.i.) 0.29 to 0.92; P = 0.03), a shorter hospital stay (mean difference -3.05 (95 per cent c.i. -4.09 to -2.01) days; P < 0.001) and quicker resumption of a normal diet (mean difference -27.48 (-30.96 to -23.99) h; P < 0.001). CONCLUSION: Patients with CTP grade A or B liver cirrhosis who undergo LC for symptomatic cholecystolithiasis have fewer overall postoperative complications, a shorter hospital stay and resume a normal diet more quickly than those who undergo OC.

de Goede, B., P. J. Klitsie, et al. (2013). "Meta-analysis of glue versus sutured mesh fixation for Lichtenstein inguinal hernia repair." Br J Surg.

BACKGROUND: Chronic pain remains a frequent complication after Lichtenstein inguinal hernia repair. As a consequence, mesh fixation using glue instead of sutures has become popular. This meta-analysis aimed to clarify which fixation technique is to be preferred for elective Lichtenstein inguinal hernia repair. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and April 2012 were searched for in MEDLINE, Embase and the Cochrane Library. Randomized controlled trials (RCTs) comparing glue and sutured mesh fixation in elective Lichtenstein repair for unilateral inguinal hernia were included. The quality of the RCTs and the potential risk of bias were assessed using the Cochrane risk of bias tool. RESULTS: Of 254 papers found in the initial search, a meta-analysis was conducted of seven RCTs comprising 1185 patients. With the use of glue mesh fixation, the duration of operation was shorter (mean difference -2.57 (95 per cent confidence interval (c.i.) -4.88 to -0.26) min; P = 0.03), patients had lower visual analogue scores for postoperative pain (mean difference -0.75 (-1.18 to -0.33); P = 0.001), early chronic pain occurred less often (risk ratio 0.52, 95 per cent c.i. 0.31 to 0.87; P = 0.01), and time to return to daily activities was shorter (mean difference -1.17 (-2.30 to -0.03) days; P = 0.04). The hernia recurrence rate did not differ significantly. CONCLUSION: Elective Lichtenstein repair for inguinal hernia using glue mesh fixation compared with sutures is faster and less painful, with comparable hernia recurrence rates.

de Hundt, M., F. Vlemmix, et al. (2013). "Comment on: a meta-analysis of common risk factors associated with the diagnosis of developmental dysplasia of the hip in newborns." Eur J Radiol 82(1): 199.

de Jong, M. C., T. S. Genders, et al. (2013). ""Reply to letter to the editor re: diagnostic performance of stress myocardial perfusion imaging for coronary artery disease: a systematic review and meta-analysis"." Eur Radiol 23(2): 349-50.

de la Hunty, A., S. Gibson, et al. (2013). "Does Regular Breakfast Cereal Consumption Help Children and Adolescents Stay Slimmer? A Systematic Review and Meta-Analysis." Obes Facts 6(1): 70-85.

Objective: To review systematically the evidence on breakfast cereal consumption and obesity in children and adolescents and assess whether the regular consumption of breakfast cereals could help to prevent excessive weight gain. Methods: A systematic review and meta-analysis of studies relating breakfast cereal consumption to BMI, BMI z-scores and prevalence of obesity as the outcomes. Results: 14 papers met the inclusion criteria. The computed effect size for mean BMI between high consumers and low or non-consumers over all 25 study subgroups was -1.13 kg/m2 (95% CI -0.81, -1.46, p < 0.0001) in the random effects model, which is equivalent to a standardised mean difference of 0.24. Adjustment for age and publication bias attenuated the effect sizes somewhat but they remained statistically significant. The prevalence and risk of overweight was lower in children and adolescents who consume breakfast cereals regularly compared to those who consume them infrequently. Energy intakes tended to be higher in regular breakfast cereal consumers. Conclusion: Overall, the evidence reviewed is suggestive that regular consumption of breakfast cereals results in a lower BMI and a reduced likelihood of being overweight in children and adolescents. However, more evidence from long-term trials and investigations into mechanisms is needed to eliminate possible confounding factors and determine causality. Copyright (c) 2013 S. Karger GmbH, Freiburg.

de Maleissye, M. F., A. Beauchet, et al. (2013). "Sunscreen use and melanocytic nevi in children: a systematic review." Pediatr Dermatol 30(1): 51-9.

We conducted a systematic review of the association between melanocytic nevi (MN) in childhood and sunscreen use. A bibliographic search was conducted between November 2008 and January 2009 using the following key words on MEDLINE and EMBASE: child*, in combination with naevi, nevi, naevus, nevus and sunscreen, sun protection. We also used Medical Subject Headings [sunscreening agents], or [radiation protection] with [nevus, pigmented]. A first screening was done on title and abstract reading. Randomized trials and cohort and cross-sectional studies analyzing the relationship between the use of sunscreen and MN in children were selected. Three reviewers abstracted data from each article. The three sets of results were compared for concordance and rereviewed if necessary. Fifteen articles were included (20,743 children). The studies were not consistent in terms of the ages of the children, MN count methods, or sunscreen use assessment. Owing to this heterogeneity, we were unable to pool the studies and conduct a meta-analysis. Twelve studies did not report that the use of sunscreen had a protective effect against MN development. Three studies reported a lower MN count when sunscreen was applied. This systematic review underlines the methodologic differences between studies. Eight of 15 studies reported a positive association between sunscreen application and MN count. Differences in MN counts, overexposure to sun, and inadequate sunscreen application on fair-skinned children could explain the disparity in the results. There is still no evidence of a protective effect of sunscreen against MN development in children.

de Martino, M., A. Haitel, et al. (2013). "The CASP8 -652 6N insertion/deletion promoter polymorphism is associated with renal cell carcinoma risk and metastasis." J Urol.

PURPOSE: Caspase-8 (Casp8) is a key regulator of apoptosis, and its cancer-cell antigen induced cell death activity is strongly impacted by the insertion/deletion promoter polymorphism CASP8 -652 6N ins/del (rs3834129). The purpose of this study was to associate this polymorphism with renal cell carcinoma (RCC) risk and pathology. METHODS: In this hospital-based case-control study, 500 Austrian patients were genotyped, including 250 with RCC and 250 age- and gender-matched healthy controls. PCR-amplified genomic DNA was evaluated with restriction fragment length polymorphism analysis and automatic sequencing. Associations with RCC risk and pathological factors were assessed. A meta-analysis of the literature was performed. RESULTS: The CASP8 -652 6N ins/del polymorphism was significantly linked with RCC (chi(2) for trend=9.50, p=0.002). Compared with ins/ins, del/del was associated with a 57% reduced risk for the disease (OR 0.43, 95% CI 0.26-0.73, p=0.002). Further, del/del was associated with a lower risk of distant metastases (p<0.05), but not with T stage, N stage, and grade. In the meta-analysis, the CASP8 -652 6N ins/del polymorphism was associated with the risk for RCC (p<0.001). CONCLUSIONS: The del/del genotype of the CASP8 -652 6N ins/del promoter polymorphism lowers the overall risk for RCC and may be associated with a decreased risk for metastasis. Larger studies are warranted to validate our findings.

de Moraes, V. Y., K. Godin, et al. (2013). "Influence of compensation status on time off work after carpal tunnel release and rotator cuff surgery: a meta-analysis." Patient Saf Surg 7(1): 1.

BACKGROUND: The assessment of post-surgical outcomes among patients with Workers' Compensation is challenging as their results are typically worse compared to those who do not receive this compensation. These patients' time to return to work is a relevant outcome measure as it illustrates the economic and social implications of this phenomenon. In this meta-analysis we aimed to assess the influence of this factor, comparing compensated and non-compensated patients. FINDINGS: Two authors independently searched MEDLINE (Ovid), Embase (Ovid), CINAHL, Google Scholar, LILACS and the Cochrane Library and also searched for references from the retrieved studies. We aimed to find prospective studies that compared carpal tunnel release and elective rotator cuff surgery outcomes for Workers' Compensation patients versus their non-compensated counterparts. We assessed the studies' quality using the Guyatt & Busse Risk of Bias Tool. Data collection was performed to depict included studies characteristics and meta-analysis. Three studies were included in the review. Two of these studies assessed the outcomes following carpal tunnel release while the other focused on rotator cuff repair. The results demonstrated that time to return to work was longer for patients that were compensated and that there was a strong association between this outcome and compensation status - Standard Mean Difference, 1.35 (IC 95%; 0.91-1.80, p < 0.001). CONCLUSIONS: This study demonstrated that compensated patients have a longer return to work time following carpal tunnel release and elective rotator cuff surgery, compared to patients who did not receive compensation. Surgeons and health providers should be mindful of this phenomenon when evaluating the prognosis of a surgery for a patient receiving compensation for their condition. TYPE OF STUDY/LEVEL OF EVIDENCE: Meta-analysis of prospective Studies/ Level III.

De Oliveira, G. S., Jr., L. J. Castro-Alves, et al. (2013). "Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials." Anesth Analg 116(1): 58-74.

BACKGROUND: Dexamethasone has an established role in decreasing postoperative nausea and vomiting (PONV); however, the optimal dexamethasone dose for reducing PONV when it is used as a single or combination prophylactic strategy has not been clearly defined. In this study, we evaluated the use of 4 mg to 5 mg and 8 mg to 10 mg IV doses of dexamethasone to prevent PONV when used as a single drug or as part of a combination preventive therapy. METHODS: A wide search was performed to identify randomized clinical trials that evaluated systemic dexamethasone as a prophylactic drug to reduce postoperative nausea and/or vomiting. The effects of dexamethasone dose were evaluated by pooling studies into 2 groups: 4 mg to 5 mg and 8 mg to 10 mg. The first group represents the suggested dexamethasone dose to prevent PONV by the Society for Ambulatory Anesthesia (SAMBA) guidelines, and the second group represents twice the dose range recommended by the guidelines. The SAMBA guidelines were developed in response to studies, which have been performed to examine different dosages of dexamethasone. RESULTS: Sixty randomized clinical trials with 6696 subjects were included. The 4-mg to 5-mg dose dexamethasone group experienced reduced 24-hour PONV compared with control, odds ratio (OR, 0.31; 95% confidence interval [CI], 0.23-0.41), and number needed to treat (NNT, 3.7; 95% CI, 3.0-4.7). When used together with a second antiemetic, the 4-mg to 5-mg dexamethasone group also experienced reduced 24-hour PONV compared with control (OR, 0.50; 95% CI, 0.35-0.72; NNT, 6.6; 95% CI, 4.3-12.8). The 8-mg to 10-mg dose dexamethasone group experienced decreased 24-hour PONV compared with control (OR, 0.26; 95% CI, 0.20-0.32; NNT, 3.8; 95% CI, 3.0-4.3). Asymmetric funnel plots were observed in the 8-mg to 10-mg dose analysis, suggesting the possibility of publication bias. When used together with a second antiemetic, the 8-mg to 10-mg dose group also experienced reduced incidence of 24-hour PONV (OR, 0.35; 95% CI, 0.22-0.53; NNT, 6.2; 95% CI, 4.5-10). In studies that provided a direct comparison between groups, there was no clinical advantage of the 8-mg to 10-mg dexamethasone dose compared with the 4-mg to 5-mg dose on the incidence of postoperative nausea and/or vomiting. CONCLUSIONS: Our results showed that a 4-mg to 5-mg dose of dexamethasone seems to have similar clinical effects in the reduction of PONV as the 8-mg to 10-mg dose when dexamethasone was used as a single drug or as a combination therapy. These findings support the current recommendation of the SAMBA guidelines for PONV, which favors the 4-mg to 5-mg dose regimen of systemic dexamethasone.

De, P., A. Farley, et al. (2013). "Systematic review and meta-analysis: influence of smoking cessation on incidence of pneumonia in HIV." BMC Med 11(1): 15.

ABSTRACT: BACKGROUND: Smoking is common in people infected with HIV but cessation support is not a routine part of clinical care. The aim was to assess whether smoking is a risk factor for pneumonia in people with HIV and whether smoking cessation ameliorates excess risk. METHODS: We performed MEDLINE and Embase database searches and included cohort or case-control studies conducted in adult patients infected with HIV extracting a hazard ratio (HR) or odds ratio (OR) that compared the incidence of bacterial pneumonia or pneumonia caused by Pneumocystis jiroveci (PCP) between two smoking categories. Studies were appraised for quality and combined using inverse variance meta-analysis. RESULTS: Fourteen cohort and case-control studies were included. Assessment of outcome was good, but assessment of exposure status was poor. Current smokers were at higher risk of bacterial pneumonia than former smokers: HR 1.37 (95% confidence interval (CI): 1.06, 1.78). There was no evidence that former smokers were at higher risk than never smokers: HR 1.24 (95%CI: 0.96, 1.60). Current smokers were at higher risk of bacterial pneumonia than current non-smokers: HR of 1.73 (95%CI: 1.44, 2.06). There was no evidence that smoking increased the incidence of PCP. The HR for current versus non-smokers was 0.94 (95%CI: 0.79, 1.12), but from case-control studies the OR was 1.76 (95%CI: 1.25, 2.48) with heterogeneity. Confined to higher quality studies, the OR was 0.97 (95%CI: 0.81, 1.16). Residual confounding is possible, but available data suggest this is not an adequate explanation. CONCLUSIONS: Smoking is a risk factor for bacterial pneumonia but not PCP and smoking cessation reduces this risk. See related article:

de Souza, B. M., L. A. Brondani, et al. (2013). "Associations between UCP1 -3826A/G, UCP2 -866G/A, Ala55Val and Ins/Del, and UCP3 -55C/T polymorphisms and susceptibility to type 2 diabetes mellitus: case-control study and meta-analysis." PLoS One 8(1): e54259.

BACKGROUND: Some studies have reported associations between five uncoupling protein (UCP) 1-3 polymorphisms and type 2 diabetes mellitus (T2DM). However, other studies have failed to confirm the associations. This paper describes a case-control study and a meta-analysis conducted to attempt to determine whether the following polymorphisms are associated with T2DM: -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3). METHODS: The case-control study enrolled 981 T2DM patients and 534 nondiabetic subjects, all of European ancestry. A literature search was run to identify all studies that investigated associations between UCP1-3 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast, additive, recessive, dominant and co-dominant inheritance models. Sensitivity analyses were performed after stratification by ethnicity. RESULTS: In the case-control study the frequencies of the UCP polymorphisms did not differ significantly between T2DM and nondiabetic groups (P>0.05). Twenty-three studies were eligible for the meta-analysis. Meta-analysis results showed that the Ala55Val polymorphism was associated with T2DM under a dominant model (OR = 1.27, 95% CI 1.03-1.57); while the -55C/T polymorphism was associated with this disease in almost all genetic models: allele contrast (OR = 1.17, 95% CI 1.02-1.34), additive (OR = 1.32, 95% CI 1.01-1.72) and dominant (OR = 1.18, 95% CI 1.02-1.37). However, after stratification by ethnicity, the UCP2 55Val and UCP3 -55C/T alleles remained associated with T2DM only in Asians (OR = 1.25, 95% CI 1.02-1.51 and OR = 1.22, 95% CI 1.04-1.44, respectively; allele contrast model). No significant association of the -3826A/G, -866G/A and Ins/Del polymorphisms with T2DM was observed. CONCLUSIONS: In our case-control study of people with European ancestry we were not able to demonstrate any association between the UCP polymorphisms and T2DM; however, our meta-analysis detected a significant association between the UCP2 Ala55Val and UCP3 -55C/T polymorphisms and increased susceptibility for T2DM in Asians.

de Steenhuijsen Piters, W. A., A. Algra, et al. (2013). "Seasonal and meteorological determinants of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis." J Neurol 260(2): 614-9.

Many studies have assessed the relationships between seasonal or meteorological determinants and the occurrence of aneurysmal subarachnoid hemorrhage (SAH), but the data are conflicting. We systematically searched the literature and meta-analyzed data from all relevant articles when possible. We searched MEDLINE (1966-2011), EMBASE (1980-2011) and the Cochrane Library to identify all observational studies examining the relationship between seasonal and meteorological determinants (temperature, atmospheric pressure and relative humidity) and the occurrence of SAH. Two authors independently extracted data from articles that were included based on predefined criteria. We pooled relative risks (RR's) with corresponding 95 % confidence intervals (CI's) from the individual studies on season and month by means of the random effects method. We included 48 articles, totaling 72,694 patients. SAH occurred less often in summer than in winter (RR 0.89, 95 % CI 0.83-0.96), and was statistically significant more often in January than in the summer months of June-September. For atmospheric pressure seven of 17 studies found a significant association, six of 18 studies were significant for temperature, and three of 15 studies were significant for humidity, but the direction of these associations was conflicting and data on these determinants were too heterogeneous to pool. Seasons influence the occurrence of SAH, with SAH occurring less often in summer than in winter, and most often in January. The explanation for the seasonal differences remains uncertain, due to the lack of sound data on the influence of meteorological factors on SAH occurrence.

de Waal, Y. C., A. J. van Winkelhoff, et al. (2013). "Differences in peri-implant conditions between fully and partially edentulous subjects: a systematic review." J Clin Periodontol 40(3): 266-86.

AIM: The aim of this study was to compare peri-implant conditions between fully edentulous (FES) and partially edentulous subjects (PES). MATERIAL AND METHODS: A systematic review was conducted. The MEDLINE, EMBASE and COCHRANE databases were searched for publications up to January 1st 2012. Studies reporting on the bleeding tendency of the peri-implant mucosa and/or studies reporting on the prevalence of peri-implant mucositis and/or peri-implantitis were considered. RESULTS: Fifty-five publications describing 46 studies were selected. One study described both FES and PES, and all other studies described either FES or PES. Subgroup analyses were performed according to dental status (fully/partially edentulous), follow-up time (>/=5 years and >/= 10 years) and study design (prospective/cross-sectional). FES harboured more plaque at their implants than PES. Modified bleeding index scores were significantly higher in FES, but no differences in bleeding on probing, implant loss and probing pocket depth were observed between FES and PES. No meta-analysis could be performed on prevalence of peri-implant mucositis and peri-implantitis. Overall prevalence of peri-implantitis was 0-3.4% after 5 years and 5.8-16.9% after 10 years of implant evaluation. CONCLUSION: FES and PES show comparable implant survival rates. However, no conclusion can be drawn regarding differences in prevalence of peri-implant mucositis and peri-implantitis between FES and PES.

de Windt, T. S., G. H. Welsch, et al. (2013). "Is Magnetic Resonance Imaging Reliable in Predicting Clinical Outcome After Articular Cartilage Repair of the Knee?: A Systematic Review and Meta-analysis." Am J Sports Med.

BACKGROUND:While MRI can provide a detailed morphological evaluation after articular cartilage repair, its additional value in determining clinical outcome has yet to be determined. PURPOSE:To evaluate the correlation between MRI and clinical outcome after cartilage repair and to identify parameters that are most important in determining clinical outcome. STUDY DESIGN:Systematic review and meta-analysis. METHODS:A systematic search was performed in Embase, MEDLINE, and the Cochrane Collaboration. Articles were screened for relevance and appraised for quality. Guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement were used. Chi-square tests were performed to find variables that could determine correlation between clinical and radiological parameters. RESULTS:A total of 32 articles (total number of patients, 1019) were included. A majority (81%) were case series or cohort studies that used similar standardized MRI techniques. The mean Coleman score was 63 (range, 42-96). For the majority of MRI parameters, limited or no correlation was found. Nine studies (28%) found a correlation between clinical outcome and the composite magnetic resonance observation of cartilage repair tissue (MOCART) or Henderson score and 7 (22%) with defect fill. In 5 studies, a weak to moderate correlation was found between clinical outcome and the T2 index (mean Pearson coefficient r = .53). CONCLUSION:Strong evidence to determine whether morphological MRI is reliable in predicting clinical outcome after cartilage repair is lacking. Future research aiming specifically at clinical sensitivity of advanced morphological and biochemical MRI techniques after articular cartilage repair could be of great importance to the field.

de Wit, J. J., G. J. Boelm, et al. (2013). "The required sample size in vaccination-challenge experiments with infectious bronchitis virus, a meta-analysis." Avian Pathol 42(1): 9-16.

For statistical, animal welfare and financial reasons the choice of the number of chickens per group in experiments is important. This estimation, together with the number of tracheal organ cultures (TOCs) that need to be examined from each chicken in order to assess protection, should be based on the difference in level of protection that one would like to be able to detect (effect size), the expected variability of the results between and within the chickens, the desired confidence level and the power of the study. To obtain data that would facilitate this estimation, a meta-analysis was performed on the data from 18 infectious bronchitis virus (IBV) vaccination-challenge experiments performed at the Dutch Animal Health Service Deventer, the Netherlands (GD) in order to determine and quantify the source of variation in the mean level of protection of different groups. For the calculations, 137 groups of chickens were subdivided into 10 clusters based on age (young or adult), vaccination (none, homologous or heterologous), challenge (IBV or mock infected) and location of vaccination (isolator at GD or in the field). The results were used to estimate the required number of chickens per group for the different clusters using 2, 5 or 10 TOCs per chicken to be able to detect effect sizes of 6.25%, 12.5%, 25% and 50% between groups of chickens with 95% confidence (P<0.05) and 80% power. The number of chickens that was required for the mentioned effect sizes varied greatly from 2 to 650. This meta-analysis provided data that allow research workers to estimate the number of chickens that should be included in each group in order to obtain reliable results based on particular combinations of infectious bronchitis vaccination and challenge strains as defined by the presented clusters.

Deandrea, S., F. Bravi, et al. (2013). "Risk factors for falls in older people in nursing homes and hospitals. A systematic review and meta-analysis." Arch Gerontol Geriatr 56(3): 407-15.

This is a systematic review and meta-analysis aimed at providing a comprehensive and quantitative review of risk factors for falls in older people in nursing homes and hospitals. Using MEDLINE, we searched for prospective studies investigating risk factors for falls in nursing home residents (NHR) and older hospital inpatients (HI). When there were at least 3 studies investigating a factor in a comparable way in a specific setting, we computed the pooled odds ratio (OR) using random effect models. Twenty-four studies met the inclusion criteria. Eighteen risk factors for NHR and six for HI were considered, including socio-demographic, mobility, sensory, medical factors, and medication use. For NHR, the strongest associations were with history of falls (OR=3.06), walking aid use (OR=2.08) and moderate disability (OR=2.08). For HI, the strongest association was found for history of falls (OR=2.85). No association emerged with age in NHR (OR=1.00), while the OR for a 5years increase in age of HI was 1.04. Female sex was, if anything, associated with a decreased risk. A few other medical conditions and medications were also associated with a moderately increased risk. For some important factors (e.g. balance and muscle weakness), a summary estimate was not computed because the measures used in various studies were not comparable. Falls in older people in nursing homes and hospitals have multifactorial etiology. History of falls, use of walking aids and disability are strong predictors of future falls.

Dearlove, B. and D. J. Wilson (2013). "Coalescent inference for infectious disease: meta-analysis of hepatitis C." Philos Trans R Soc Lond B Biol Sci 368(1614): 20120314.

Genetic analysis of pathogen genomes is a powerful approach to investigating the population dynamics and epidemic history of infectious diseases. However, the theoretical underpinnings of the most widely used, coalescent methods have been questioned, casting doubt on their interpretation. The aim of this study is to develop robust population genetic inference for compartmental models in epidemiology. Using a general approach based on the theory of metapopulations, we derive coalescent models under susceptible-infectious (SI), susceptible-infectious-susceptible (SIS) and susceptible-infectious-recovered (SIR) dynamics. We show that exponential and logistic growth models are equivalent to SI and SIS models, respectively, when co-infection is negligible. Implementing SI, SIS and SIR models in BEAST, we conduct a meta-analysis of hepatitis C epidemics, and show that we can directly estimate the basic reproductive number (R(0)) and prevalence under SIR dynamics. We find that differences in genetic diversity between epidemics can be explained by differences in underlying epidemiology (age of the epidemic and local population density) and viral subtype. Model comparison reveals SIR dynamics in three globally restricted epidemics, but most are better fit by the simpler SI dynamics. In summary, metapopulation models provide a general and practical framework for integrating epidemiology and population genetics for the purposes of joint inference.

Debourdeau, P., D. Farge, et al. (2013). "International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer." J Thromb Haemost 11(1): 71-80.

BACKGROUND: Although long-term indwelling central venous catheters (CVCs) may lead to pulmonary embolism (PE) and loss of the CVC, there is lack of consensus on management of CVC-related thrombosis (CRT) in cancer patients and heterogeneity in clinical practices worldwide. OBJECTIVES: To establish common international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer patients. METHODS: An international working group of experts was set up to develop GCPG according to an evidence-based medicine approach, using the GRADE system. RESULTS: For the treatment of established CRT in cancer patients, we found no prospective randomized studies, two non-randomized prospective studies and one retrospective study examining the efficacy and safety of low-molecular-weight heparin (LMWH) plus vitamin K antagonists (VKAs). One retrospective study evaluated the benefit of CVC removal and two small retrospective studies were on thrombolytic drugs. For the treatment of symptomatic CRT, anticoagulant treatment (AC) is recommended for a minimum of 3 months; in this setting, LMWHs are suggested. VKAs can also be used, in the absence of direct comparisons of these two types of anticoagulants in this setting [Guidance]. The CVC can be kept in place if it is functional, well-positioned and non-infected and there is good resolution under close surveillance; whether the CVC is kept or removed, no standard approach in terms of AC duration has been established [Guidance]. For the prophylaxis of CRT in cancer patients, we found six randomized studies investigating the efficacy and safety of VKA vs. placebo or no treatment, one on the efficacy and safety of unfractionnated heparin, six on the value of LMWH, one double-blind randomized and one non randomized study on thrombolytic drugs and six meta-analyses of AC and CVC thromboprophylaxis. Type of catheter (open-ended like the Hickman((R)) catheter vs. closed-ended catheter with a valve like the Groshong((R)) catheter), its position (above, below or at the junction of the superior vena cava and the right atrium) and method of placement may influence the onset of CRT on the basis of six retrospective trials, four prospective non-randomized trials, three randomized trials and one meta-analysis. In light of these data: use of AC for routine prophylaxis of CRT is not recommended [1A]; a CVC should be inserted on the right side, in the jugular vein, and distal extremity of the CVC should be located at the junction of the superior vena cava and the right atrium [1A]. CONCLUSION: Dissemination and implementation of these international GCPG for the prevention and treatment of CRT in cancer patients at each national level is a major public health priority, needing worldwide collaboration.

Debray, T. P., K. G. Moons, et al. (2013). "A framework for developing, implementing, and evaluating clinical prediction models in an individual participant data meta-analysis." Stat Med.

The use of individual participant data (IPD) from multiple studies is an increasingly popular approach when developing a multivariable risk prediction model. Corresponding datasets, however, typically differ in important aspects, such as baseline risk. This has driven the adoption of meta-analytical approaches for appropriately dealing with heterogeneity between study populations. Although these approaches provide an averaged prediction model across all studies, little guidance exists about how to apply or validate this model to new individuals or study populations outside the derivation data. We consider several approaches to develop a multivariable logistic regression model from an IPD meta-analysis (IPD-MA) with potential between-study heterogeneity. We also propose strategies for choosing a valid model intercept for when the model is to be validated or applied to new individuals or study populations. These strategies can be implemented by the IPD-MA developers or future model validators. Finally, we show how model generalizability can be evaluated when external validation data are lacking using internal-external cross-validation and extend our framework to count and time-to-event data. In an empirical evaluation, our results show how stratified estimation allows study-specific model intercepts, which can then inform the intercept to be used when applying the model in practice, even to a population not represented by included studies. In summary, our framework allows the development (through stratified estimation), implementation in new individuals (through focused intercept choice), and evaluation (through internal-external validation) of a single, integrated prediction model from an IPD-MA in order to achieve improved model performance and generalizability. Copyright (c) 2013 John Wiley & Sons, Ltd.

Degner, J. and J. Dalege (2013). "The Apple Does Not Fall Far From the Tree, or Does It? A Meta-Analysis of Parent-Child Similarity in Intergroup Attitudes." Psychol Bull.

Understanding the formation of prejudice, stereotypes, and discrimination has long been a core topic of social psychology. Since the seminal theorizing by Allport in 1954, different views on childhood origins of prejudice have been discussed, in which the role of parental socialization varies on a scale from fundamental to negligible. This meta-analysis integrates the available empirical evidence of the past 60 years and critically discusses the current state of knowledge on parental socialization of intergroup attitudes. A random-effects model analysis of data from 131 studies on over 45,000 parent-child dyads indicated a significant medium-sized average effect size for the correlation between parental and child intergroup attitudes. The average effect size was related to study-specific variables, such as the source of parental attitude report (self vs. child reported), the conceptual overlap between measures, and the privacy of assessment. We also found significant moderations by ingroup status and size as well as child age. The latter was, however, mediated by measurement overlap. No significant effect size differences were found in relation to different components of intergroup attitudes (i.e., affective, cognitive, behavioral), nor to child or parent gender. The results unequivocally demonstrate that parent-child attitudes are related throughout childhood and adolescence. We discuss in detail whether and to what extent this interrelation can be interpreted as an indicator of parent-child socialization to allow a critical evaluation of the available contradicting theories. We furthermore address limitations of the available research and the current meta-analysis and derive implications and suggestions for future research. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Del Campo, J. and I. Ruiz-Trillo (2013). "Environmental Survey Meta-analysis Reveals Hidden Diversity among Unicellular Opisthokonts." Mol Biol Evol.

The Opisthokonta clade includes Metazoa, Fungi, and several unicellular lineages, such as choanoflagellates, filastereans, ichthyosporeans, and nucleariids. To date, studies of the evolutionary diversity of opisthokonts have focused exclusively on metazoans, fungi, and, very recently, choanoflagellates. Thus, very little is known about diversity among the filastereans, ichthyosporeans, and nucleariids. To better understand the evolutionary diversity and ecology of the opisthokonts, here we analyze published environmental data from nonfungal unicellular opisthokonts and report 18S ribosomal DNA phylogenetic analyses. Our data reveal extensive diversity among all unicellular opisthokonts, except for the filastereans. We identify several clades that consist exclusively of environmental sequences, especially among ichthyosporeans and choanoflagellates. Moreover, we show that the ichthyosporeans represent a significant percentage of overall unicellular opisthokont diversity, with a greater ecological role in marine environments than previously believed. Our results provide a useful phylogenetic framework for future ecological and evolutionary studies of these poorly known lineages.

Del Re, A. C., N. Maisel, et al. (2013). "The Declining Efficacy of Naltrexone Pharmacotherapy for Alcohol Use Disorders Over Time: A Multivariate Meta-Analysis." Alcohol Clin Exp Res.

BACKGROUND: Oral naltrexone is an FDA-approved medication for treating alcohol use disorders. Although its efficacy has been supported in multiple clinical trials, an earlier review found that its effect sizes (ESs) on relapse to heavy drinking and, to a lesser extent, percent days drinking were smaller in more recent trials and in multicenter than in single-site studies. We examined whether these findings held when studies from 2004 to 2009 were taken into account, and whether single-site versus multicenter trials, the use of placebo run-in periods, and placebo group improvement accounted for variation in naltrexone effects and decreasing effects over time. METHODS: A multivariate meta-analysis of naltrexone pharmacotherapy trials for alcohol use disorders was conducted. All analyses simultaneously modeled ESs on outcomes of percent days abstinent and relapse to heavy drinking. Potential moderators of medication effects that were examined included publication year, multicenter design (vs. single site), placebo run-in period, and placebo group improvement. RESULTS: Statistically significant between-group differences on percent days abstinent (the inverse of percent days drinking) and relapse to heavy drinking favored naltrexone over placebo. Year of publication was a significant moderator for both outcomes, with more recent trials having smaller ESs. Neither multi- versus single-site study, the interaction between multi- versus single-site study and year of publication, nor placebo run-in period was a significant moderator of naltrexone effects. Although placebo group improvement was modestly associated with smaller between-group naltrexone versus placebo ESs, only 21 studies provided usable information on placebo group improvement. Within those studies, there was no relationship between naltrexone ESs and time, so placebo group improvement was not examined as a moderator of that relationship. CONCLUSIONS: Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.

Del-Aguila, J. L., A. L. Beitelshees, et al. (2013). "Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans." Pharmacogenomics J.

Hydrochlorothiazide (HCTZ) is one of the most widely prescribed antihypertensive medications. Although it is well known that HCTZ is associated with hyperglycemia and hypertriglyceridemia, the mechanisms underlying these adverse effects are not well understood. We performed a genome-wide association study and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses and the Genetic Epidemiology of Responses to Antihypertensive studies. Two single-nucleotide polymorphisms (rs12279250 and rs4319515 (r(2)=0.73)), located at 11p15.1 in the NELL1 gene, achieved genome-wide significance for association with change in fasting plasma triglycerides in African Americans, whereby each variant allele was associated with a 28 mg dl(-1) increase in the change in triglycerides. NELL1 encodes a cytoplasmic protein that contains epidermal growth factor-like repeats and has been shown to represses adipogenic differentiation. These findings may represent a novel mechanism underlying HCTZ-induced adverse metabolic effects.The Pharmacogenomics Journal advance online publication, 12 February 2013; doi:10.1038/tpj.2013.3.

Delahanty, R. J., A. Beeghly-Fadiel, et al. (2013). "Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women." Hum Reprod.

STUDY QUESTION: Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry? SUMMARY ANSWER: Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women. PARTICIPANTS AND SETTING: We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche. MAIN RESULTS: For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 x 10(-6), binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche approximately 5 months later than those in the lowest quintile. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results. STUDY FUNDING/COMPETING INTERESTS: This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.

Delewi, R., A. Andriessen, et al. (2013). "Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a meta-analysis of randomised controlled clinical trials." Heart 99(4): 225-32.

CONTEXT: Numerous randomized controlled studies assessing intracoronary bone marrow cell therapy (BMC) after acute myocardial infarction (AMI) have been performed. OBJECTIVE: To systematically review the effect of autologous BMC therapy on left ventricular function by performing an up to date meta-analysis of randomized controlled trials (RCTs) including long-term follow-up. DATA SOURCES: Trials were indentified through a literature search from 1980 to June 2012 of the Pubmed, Embase, Cochrane database, and the Current Controlled Trials Register. STUDY SELECTION: Randomized clinical trials comparing intracoronary BMC infusion to control as treatment for AMI. DATA EXTRACTION: The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to follow-up. Secondary endpoints were changes in left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), infarct size and clinical outcomes. RESULTS: Improvement of LVEF in patients receiving intracoronary BMC was significantly better within 6 months (23 studies, 2.23% (95% confidence interval (CI) 1.00 to 3.47); p<0.001). At 12 months of follow-up, this effect sustained with 3.91% more LVEF improvement (11 studies, (95% CI 2.56 to 5.27), p<0.001). At long-term follow-up, we found a trend for better LVEF improvement in favor of cell therapy (7 studies, 1.90% (95% CI -0.43 to 4.23); p=0.11). There was no clear effect in infarct size or LVEDV. However, we found a significant reduction in LVESV at 6 months (-4.81 ml (95% CI -7.86 to -1.76); p<0.001 and at 12 months (-9.41 ml (95% CI -13.64 to -5.17); p<0.001). Moreover, there was a statistically significant decrease in recurrent AMI (Relative Risk (RR) 0.44 (95% CI 0.24 to 0.79); p=0.007), and readmission for heart failure, unstable angina or chest pain (RR 0.59 (95% CI 0.35 to 0.98); p=0.04) in favour of cell therapy. CONCLUSION: Intracoronary BMC treatment leads to a moderate improvement of LVEF and reduction of LVESV at 6 months that sustained at 12 months follow-up, without a clear significant effect on LVEDV, or infarct size. Furthermore, we found that intracoronary cell therapy is significantly associated with a reduction in recurrent AMI and readmission for heart failure, unstable angina or chest pain.

Delvecchio, G., G. Sugranyes, et al. (2013). "Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies." Psychol Med 43(3): 553-69.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology and phenomenology but differ with regard to emotional processing. We used facial affect as a probe for emotional processing to determine whether there are diagnosis-related differences between SZ and BD in the function of the underlying neural circuitry. METHOD: Functional magnetic resonance imaging (fMRI) studies published up to 30 April 2012 investigating facial affect processing in patients with SZ or BD were identified through computerized and manual literature searches. Activation foci from 29 studies encompassing 483 healthy individuals, 268 patients with SZ and 267 patients with BD were subjected to voxel-based quantitative meta-analysis using activation likelihood estimation (ALE). RESULTS: Compared to healthy individuals, when emotional facial stimuli were contrasted to neutral stimuli, patients with BD showed overactivation within the parahippocampus/amygdala and thalamus and reduced engagement within the ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed underactivation throughout the entire facial affect processing network and increased activation in visual processing regions within the cuneus. Patients with BD showed greater thalamic engagement compared to patients with SZ; in the reverse comparison, patients with SZ showed greater engagement in posterior associative visual cortices. CONCLUSIONS: During facial affect processing, patients with BD show overactivation in subcortical regions and underactivation in prefrontal regions of the facial affect processing network, consistent with the notion of reduced emotional regulation. By contrast, overactivation within visual processing regions coupled with reduced engagement of facial affect processing regions points to abnormal visual integration as the core underlying deficit in SZ.

den Hoed, M., J. Luan, et al. (2013). "Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples." Int J Obes (Lond) 37(2): 191-6.

Background:Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.Objective:We aimed to validate association of these variants with obesity-related traits in population-based samples.Design:Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.Results:We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (beta=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).Conclusion:Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.

Deng, J. S., P. Qin, et al. (2013). "Association between interleukin-1beta C (3953/4)T polymorphism and chronic periodontitis: Evidence from a meta-analysis." Hum Immunol 74(3): 371-8.

The aim of this study was to perform a meta-analysis to evaluated the association between interleukin-1beta (IL-1beta) C(3953/4)T polymorphism and chronic periodontitis (CP). Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase and Web of Science. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Publication bias was tested by Begg's funnel plot and Egger's regression test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE) or high quality (score7). Data analyses were carried out by Stata 11.0. There were significant associations between IL-1beta C(3953/4)T polymorphism and CP (for T allele vs. C allele: OR=1.30, 95%CI=1.05-1.60, p=0.02; for T/T vs. C/C: OR=1.66, 95%CI=1.12-2.45, p=0.01; for C/T+T/T vs. C/C: OR=1.28, 95%CI=0.99-1.65; and for T/T vs. C/T+C/C: OR=1.62, 95%CI=1.15-2.29, p=0.006). When stratified by ethnicity, statistically significantly elevated risk was found for Caucasians, but not for Asians. When stratified by study design, evidences of significant association was observed between IL-1beta C(3953/4)T polymorphism and CP in both population-based studies and hospital-based studies. This meta-analysis indicates that there is strong evidence for association between IL-1beta C(3953/4)T polymorphism and CP.

Deng, L., J. Zhang, et al. (2013). "Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour." Cochrane Database Syst Rev 1: CD005196.

BACKGROUND: This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear. OBJECTIVES: To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN. SEARCH METHODS: For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN. DATA COLLECTION AND ANALYSIS: Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study. MAIN RESULTS: We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens. AUTHORS' CONCLUSIONS: CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.

Deng, S., B. H. May, et al. (2013). "Topical herbal medicine combined with pharmacotherapy for psoriasis: a systematic review and meta-analysis." Arch Dermatol Res.

This systematic review examines the current state of the evidence for the efficacy and safety of herbal medicines (HMs) used topically in conjunction with anti-psoriatic pharmacotherapy (APP) in the treatment of psoriasis. Searches were conducted in September 2012 of PubMed, EMBASE, Cochrane Library, two Chinese databases (China National Knowledge Infrastructure and Chinese Scientific Journals Full Text Database) and of article reference lists. We included randomized controlled trials published in English, Chinese or Japanese that investigated topical HM combined with APP used systemically and/or topically compared to pharmacotherapy alone. Studies employing phototherapy were excluded. Two authors conducted searches, extracted data on study characteristics and outcomes, and assessed Risk of Bias. Disagreements were resolved by discussion with a third author. Eight studies met the inclusion criteria. All used multi-herb formulae, four in herbal baths, three in herbal ointments or creams, and one as herbal steam. The pooled data indicated a benefit for the add-on effect of herbal therapy to APP. Adding these topical HMs to conventional pharmacotherapy appeared to produce short-term additional clinical benefits. No serious adverse events were reported. Experimental studies suggest that some of the herbs possess anti-inflammatory, anti-pruritic, and/or anti-proliferative activities. However, these results need to be interpreted with caution due to methodological weaknesses and the lack of replicated studies. Studies that address the identified methodological deficiencies are required to further investigate the efficacy and safety of these HMs as adjunct therapies for psoriasis.

Dentali, F., A. P. Sironi, et al. (2013). "Relationship between ABO Blood Group and Hemorrhage: A Systematic Literature Review and Meta-Analysis." Semin Thromb Hemost 39(1): 72-82.

Several studies have suggested that patients with non-O blood group have an increased risk of both venous and arterial thromboembolic events. On the contrary, the role of ABO blood group on the risk of bleeding complications remains unclear. Thus, we performed a meta-analysis of the literature with the aim of assessing this potential association. MEDLINE and Embase databases were searched from 1946 to March 2012. Studies comparing the prevalence of different ABO blood groups in bleeding patients as well as in controls without bleeding complications were potentially includible. Two reviewers independently selected studies and extracted study characteristics, quality, and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a random-effects model. Twenty-two studies totalling 9,468 bleeding patients and more than 450,000 controls were included. The prevalence of O blood group was significantly higher in bleeding patients than in controls, with a resulting pooled OR of 1.33 (95% CI = 1.25 to 1.42; p < 0.001). The result of this meta-analysis of a very large sample of bleeding patients and controls suggests that O blood group is a potentially important genetic risk factor for bleeding. High-quality prospective studies are warranted to confirm these preliminary findings.

Deo, R., M. A. Nalls, et al. (2013). "Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants." Heart Rhythm 10(3): 401-8.

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P</=2.5x10). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98x10). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Deppe, A. C., O. J. Liakopoulos, et al. (2013). "Endoscopic vein harvesting for coronary artery bypass grafting: a systematic review with meta-analysis of 27,789 patients." J Surg Res 180(1): 114-24.

BACKGROUND: To determine the current strength of evidence for or against endoscopic vein harvesting (EVH) in patients undergoing coronary artery bypass grafting (CABG). MATERIALS AND METHODS: A meta-analysis of randomized controlled trials (RCT) and observational trials (OT) was performed that reported the impact of EVH on adverse clinical outcomes after CABG. Analyzed postoperative outcomes included wound infection, postoperative pain, myocardial infarction (MI), vein graft failure, length of hospital stay, and mortality. Pooled treatment effects (OR or weighted mean difference (WMD), 95%CI) were assessed using a fixed or random effects model. RESULTS: A total of 27,789 patients from 43 studies (16 RCT, 27 OT) were identified who underwent saphenectomy by endoscopic (46%; n = 12,822) or conventional technique (54%; n = 14,967). Pooled effect estimates revealed a reduced incidence (P < 0.001) for wound infections (OR 0.27; 95% CI 0.22 to 0.32), pain (WMD -1.26, 95% CI -2.07 to -0.44; P = 0.0026), and length of hospital stay (WMD -0.6 d, 95% CI -1.08 to -0.12; P = 0.0152). EVH was associated to an increase of the odds for vein graft failure (OR 1.38; 95% CI 1.01 to 1.88; P = 0.0433), a finding that lost statistical difference after pooled analysis of RCT and studies with high methodological quality. Similarly, graft-related endpoints, including mortality and MI, did not differ between the harvesting techniques. CONCLUSION: The present systematic review underscores the safety of EVH in patients undergoing CABG. EVH reduces leg wound infections without increasing the midterm risk for vein graft failure, MI, or mortality.

D'Errigo, P., F. Biancari, et al. (2013). "Thirty-Day Mortality After Coronary Artery Bypass Surgery in Patients Aged <50 Years: Results of a Multicenter Study and Meta-Analysis of the Literature." J Card Surg.

BACKGROUND: Young patients requiring myocardial revascularization are considered at low operative risk, but data on their outcome are scarce. This study was undertaken to evaluate the prevalence and 30-day mortality of patients aged <50 years after isolated coronary artery bypass surgery (CABG). MATERIALS AND METHODS: This is a multicenter study including 2207 patients aged <50 years undergoing isolated CABG at 68 Italian hospitals. RESULTS: The proportion of patients aged <50 years in this series was 5.3% and varied significantly from 0% to 9.9% in different institutions (p < 0.0001). The 30-day mortality rate was 0.9%. One-to-one propensity score matching of patients aged <50 years versus older patients resulted in 2013 pairs whose 30-day mortality was 0.9% and 2.2%, respectively (p = 0.001). Logistic regression showed that left ventricular ejection fraction <30% (OR 5.5, 95% CI 1.6-18.6), peripheral vascular disease (OR 3.6, 95% CI 1.1-12.0), pulmonary hypertension (OR 18.1, 95% CI 1.8-187.0), critical preoperative state (OR 4.7, 95% CI 1.5-14.3), and emergency operation (OR 3.8, 95% CI 1.1-12.9) were independent predictors of 30-day mortality. Meta-analysis of five studies reporting on patients aged <50 years who underwent isolated CABG showed that operative mortality in these patients was 0.9% (95% CI, 0.8-1.1%, I2 0%, 135/14,316 patients). CONCLUSIONS: The proportion of patients aged <50 years undergoing CABG is low and varies significantly among institutions. The results of this study and a meta-analysis of the literature data showed that CABG can be carried out in young patients with an extremely low risk of operative mortality.

Desch, K. C., A. B. Ozel, et al. (2013). "Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association." Proc Natl Acad Sci U S A 110(2): 588-93.

The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (n = 1,152 and n = 2,310) and identified signals at ABO (P < 7.9E-139) and VWF (P < 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12-2p13 (LOD score 5.3) and at the ABO locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the "missing heritability" for other complex genetic traits.

Desch, S., E. Boudriot, et al. (2013). "Bypass surgery versus percutaneous coronary intervention for the treatment of unprotected left main disease : A meta-analysis of randomized controlled trials." Herz 38(1): 48-56.

OBJECTIVE: We performed a meta-analysis of randomized controlled trials to compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for the treatment of de novo unprotected left main disease. BACKGROUND: Although CABG is accepted to be standard of care for revascularization of unprotected left main stenosis, PCI is increasingly being used as an alternative primary approach. METHODS: We searched for randomized, controlled trials comparing CABG and PCI for the treatment of unprotected left main disease. Major adverse cardiac and cerebrovascular events (all-cause death, myocardial infarction, stroke, and repeat revascularization) were analyzed. RESULTS: The search strategy identified 4 randomized controlled trials enrolling a total of 1,611 patients. Follow-up ranged between 1 and 2 years. There were no significant differences in the risk of death or myocardial infarction between the two treatment modalities. While the risk of stroke was significantly lower in patients undergoing PCI (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.10-0.69, p = 0.007), the risk of repeat revascularization was higher among patients undergoing PCI (RR 1.94, 95% CI 1.43-2.61, p < 0.001). No relevant statistical heterogeneity across studies could be found. CONCLUSION: In this largest series of randomized patients with unprotected left main stenosis to date, the risk of death and myocardial infarction was comparable between CABG and PCI. However, patients undergoing CABG had a higher risk of stroke, whereas patients undergoing PCI were at a higher risk for repeat revascularization.

Deschodt, M., J. Flamaing, et al. (2013). "Impact of geriatric consultation teams on clinical outcome in acute hospitals: a systematic review and meta-analysis." BMC Med 11(1): 48.

ABSTRACT: BACKGROUND: Comprehensive geriatric assessment for older patients admitted to dedicated wards has proven to be beneficial, but the impact of comprehensive geriatric assessment delivered by mobile inpatient geriatric consultation teams remains unclear. This review and meta-analysis aims to determine the impact of inpatient geriatric consultation teams on clinical outcomes of interest in older adults. METHODS: An electronic search of Medline, CINAHL, EMBASE, Web of Science and Invert for English, French and Dutch articles was performed from study inception to June 2012. Three independent reviewers selected prospective cohort studies assessing functional status, readmission rate, mortality or length of stay in adults aged 60 years or older. Twelve studies evaluating 4,546 participants in six countries were identified. Methodological quality of the included studies was assessed with the Methodological Index for Non-Randomized Studies. RESULTS: The individual studies show that an inpatient geriatric consultation team intervention has favorable effects on functional status, readmission and mortality rate. None of the studies found an effect on the length of the hospital stay. The meta-analysis found a beneficial effect of the intervention with regard to mortality rate at 6 months (relative risk 0.66; 95% confidence interval 0.52 to 0.85) and 8 months (relative risk 0.51; confidence interval 0.31 to 0.85) after hospital discharge. CONCLUSIONS: Inpatient geriatric consultation team interventions have a significant impact on mortality rate at 6 and 8 months postdischarge, but have no significant impact on functional status, readmission or length of stay. The reason for the lack of effect on these latter outcomes may be due to insufficient statistical power or the insensitivity of the measuring method for, for example, functional status. The questions of to whom IGCT intervention should be targeted and what can be achieved remain unanswered and require further research. Trial registration: CRD42011001420 ( Please see related commentary article here

Deshpande, A., V. Pasupuleti, et al. (2013). "Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis." J Gastroenterol Hepatol 28(2): 235-42.

BACKGROUND AND AIM: Proton pump inhibitors (PPI) and H(2) -receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid-suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP). The aim of this meta-analysis was to evaluate the association between acid-suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis. METHODS: We searched MEDLINE and four other databases for subject headings and text words related to SBP and acid-suppressive therapy. All observational studies that investigated the risk of SBP associated with PPI/H2RA therapy and utilized SBP as an endpoint were considered eligible. Data from the identified studies were combined by means of a random-effects model and odds ratios (ORs) were calculated. RESULTS: Eight studies (n = 3815 patients) met inclusion criteria. The risk of hospitalized cirrhotic patients developing SBP increased when using acid-suppressive therapy. The risk was greater with PPI therapy (n = 3815; OR 3.15, 95% confidence interval 2.09-4.74) as compared to those on H2RA therapy (n = 562; OR 1.71, 95% confidence interval 0.97-3.01). CONCLUSIONS: Pharmacologic acid suppression was associated with a greater risk of SBP in hospitalized patients with cirrhosis. Cirrhotic patients receiving a PPI have approximately three times the risk of developing SBP compared with those not receiving this medication. Prospective studies may help clarify this relationship and shed light on the mechanism(s) by which acid-suppressive therapy increases the risk of SBP in hospitalized patients with cirrhosis.

Dev Rishabh, P., G. Prem Prakash, et al. (2013). "Role of Statins in Alzheimer's disease: A retrospective meta-analysis for commonly investigated clinical parameters in RCTs." Int J Neurosci.

Abstract This review was conducted to assess role of statins in treatment of Alzheimer's Disease (AD). We conducted meta-analysis using the randomized controlled trials (RCTs) conducted in patients who suffered from Alzheimer's disease, by conducting searches for RCTs in MEDLINE, EMBASE and Cochrane (up to 2012). An overall of five studies were included and analyzed. The evaluation was done for some commonly evaluated clinical parameters like Clinical Global Impression of Change (CGIC), Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale (ADAS-CoG). Statistical evaluation was done as per method described by Neyeloff et al. and forest plots were plotted for each evaluated parameter. MMSE score showed a significant difference in favour of statins. ADAS-CoG and CGIC did not show a significant advantage for statins in comparison to placebo. Highly heterogeneous distribution was seen for MMSE score. Further trials need to be conducted to arrive at more robust results.

Dey, T., G. Brigden, et al. (2013). "Outcomes of clofazimine for the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis." J Antimicrob Chemother 68(2): 284-93.

BACKGROUND: Current anti-tuberculosis therapeutics are not sufficiently effective against drug-resistant tuberculosis (DR-TB), and there is a need for new drugs and therapeutic approaches. It has been proposed that repurposing clofazimine for DR-TB treatment might be one way to increase therapeutic options. METHODS: We conducted a systematic review of studies reporting on the efficacy and safety of clofazimine as part of combination therapy for DR-TB. Six databases and six conference abstract sites were searched from inception until April 2012. All studies involving the use of clofazimine in the treatment of DR-TB were included. RESULTS: Twelve studies, comprising 3489 patients across 10 countries, were included in this review. Treatment success ranged from 16.5% (95% CI 2.7%-38.7%) to 87.8% (95% CI 76.8%-95.6%), with an overall pooled proportion of 61.96% achieving treatment success (95% CI 52.79%-71.12%) (tau(2) 0.07). Mortality, treatment interruptions, defaulting and adverse events were all in line with DR-TB treatment outcomes overall. The most commonly reported adverse events were gastrointestinal disturbances and skin pigmentation. CONCLUSIONS: The available evidence to date suggests that clofazimine could be considered as an additional therapeutic option in the treatment of DR-TB. The optimal dose of clofazimine and duration of use require further investigation.

Di Mario, S., V. Basevi, et al. (2013). "Prenatal education for congenital toxoplasmosis." Cochrane Database Syst Rev 2: CD006171.

BACKGROUND: Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. OBJECTIVES: To assess the effects of prenatal education for preventing congenital toxoplasmosis. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 January 2012), PubMed (1966 to 15 January 2012), EMBASE (1980 to 15 January 2012), CINAHL (1982 to 15 January 2012), LILACS (1982 to 15 January 2012), IMEMR (1984 to 15 January 2012), and reference lists of relevant papers, reviews and websites. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials (RCTs) of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and study quality. Two review authors extracted data. Data were checked for accuracy. MAIN RESULTS: Two cluster-randomized controlled trials (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways which meant that meta-analysis of the results was not possible One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. The authors did not report measure of association but only provided P values (P less than 0.05) for all outcomes. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect on improving women's knowledge whereas it has no effect on changing women's behavior. In this trial 17/3949 pregnant women seroconverted for toxoplasmosis: 13/2591 (0.5%) in the intervention group and 4/1358 (0.3%) in the control group. The number of events was too small to reach conclusions about the effect of prenatal education on seroconversion rate during pregnancy.No other randomized trials on the effect of prenatal education on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during pregnancy were detected. AUTHORS' CONCLUSIONS: Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention.

Di Santo, S. G., F. Prinelli, et al. (2013). "A Meta-Analysis of the Efficacy of Donepezil, Rivastigmine, Galantamine, and Memantine in Relation to Severity of Alzheimer's Disease." J Alzheimers Dis.

BACKGROUND: Randomized clinical trials have evaluated the efficacy of acetylcholinesterase inhibitors (AChE-Is) and memantine across a wide range of Alzheimer's disease (AD) severity. However, these drugs are prescribed and reimbursed according to precise upper and lower cut off scores of cognitive tests. OBJECTIVES: To verify whether the efficacy of pharmacological treatment had any dependence on the severity of dementia in AD patients. METHODS: Published English-language randomized, placebo-controlled trials evaluating the efficacy of AChE-Is or memantine at any dose, over any length of time, in patients with any severity of dementia due to AD were included. Cognitive, behavioral, and functional outcomes were extracted from each study and multiple outcomes from the same trial were pooled to obtain a unique indicator of efficacy for cognition, functional impairment, and behavioral and psychological disturbances. The existence of a relationship between size of the treatment effect and severity of dementia, measured with the Mini-Mental State Examination, was determined using parametric and non-parametric correlation analyses. RESULTS: Both AChE-Is and memantine had significant effects on cognition. Functional and psycho-behavioral outcomes were reported less frequently but also showed significant efficacy of treatment. High heterogeneity among studies was found within and between the different drugs. The efficacy of all drugs except memantine was independent from dementia severity in all domains. Memantine effect on functional impairment was better in more severe patients. CONCLUSIONS: The modest beneficial effects of anti-dementia drugs on cognition are independent from dementia severity. Memantine is more effective on functional incompetence only in severe patients.

Diao, M., F. Huang, et al. (2013). "Prehospital therapeutic hypothermia after cardiac arrest: A systematic review and meta-analysis of randomized controlled trials." Resuscitation.

BACKGROUND: Therapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. However, the optimal time to initiate therapeutic hypothermia remains unclear. The objective of the present study is to assess the effectiveness and safety of prehospital therapeutic hypothermia after cardiac arrest. METHODS: Databases such as MEDLINE, Embase, and Cochrane Library were searched from their establishment date to May of 2012 to retrieve randomized control trials on prehospital therapeutic hypothermia after cardiac arrest. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A meta-analysis was performed by using the Cochrane Collaboration Review Manager 5.1.6 software. RESULTS: Five studies involving 633 cases were included, among which 314 cases were assigned to the treatment group and the other 319 cases to the control group. The meta-analysis indicated that prehospital therapeutic hypothermia after cardiac arrest produced significant differences in temperature on hospital admission compared with in-hospital therapeutic hypothermia or normothermia (patient data; mean difference=-0.95; 95% confidence interval -1.15 to -0.75; I2=0%). However, no significant differences were observed in the survival to the hospital discharge, favorable neurological outcome at hospital discharge, and rearrest. The risk of bias was low; however, the quality of the evidence was very low. CONCLUSION: This review demonstrates that prehospital therapeutic hypothermia after cardiac arrest can decrease temperature on hospital admission. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and rearrest, our meta-analysis and review produces non-significant results. Using the Grading of Recommendations, Assessment, Development and Evaluation methodology, we conclude that the quality of evidence is very low.

Dickson, H. G. (2013). "A meta-analysis of "hospital in the home"." Med J Aust 198(4): 195.

Dickstein, D. P., M. F. Pescosolido, et al. (2013). "Developmental meta-analysis of the functional neural correlates of autism spectrum disorders." J Am Acad Child Adolesc Psychiatry 52(3): 279-289 e16.

OBJECTIVE: There is a pressing need to elucidate the brain-behavior interactions underlying autism spectrum disorders (ASD) given the marked rise in ASD diagnosis over the past decade. Functional magnetic resonance imaging (fMRI) has begun to address this need, but few fMRI studies have evaluated age-related changes in ASD. Therefore, we conducted a developmental analysis of activation likelihood estimation (ALE) meta-analysis to compare child versus adult ASD fMRI studies. We hypothesized that children and adolescents with ASD (<18 years old) would rely less on prefrontal cortex structures than adults (>/=18 years old). METHOD: PubMed and PsycInfo literature searches were conducted to identify task-dependent fMRI studies of children or adults with ASD. Then recent GingerALE software improvements were leveraged to perform direct comparisons of child (n = 18) versus adult (n = 24) studies. RESULTS: ALE meta-analyses of social tasks showed that children and adolescents with ASD versus adults had significantly greater hyperactivation in the left post-central gyrus, and greater hypoactivation in the right hippocampus and right superior temporal gyrus. ALE meta-analyses of nonsocial tasks showed that children with ASD versus adults had significantly greater hyperactivation in the right insula and left cingulate gyrus, and hypoactivation in the right middle frontal gyrus. CONCLUSION: Our data suggest that the neural alterations associated with ASD are not static, occurring only in early childhood. Instead, children with ASD have altered neural activity compared to adults during both social and nonsocial tasks, especially in fronto-temporal structures. Longitudinal neuroimaging studies are required to examine these changes prospectively, as potential targets for brain-based treatments for ASD.

Didsbury, M., R. G. McGee, et al. (2013). "Exercise Training in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis." Transplantation.

BACKGROUND: Exercise training is effective in improving the cardiovascular risk profiles of nontransplanted patients, but the health benefits and potential harms of routine exercise training after solid organ transplantation are unclear. This study aims to assess the health benefits and harms of supervised exercise training programs in solid organ recipients. METHODS: We systematically reviewed all randomized controlled trials (RCTs) comparing the outcomes of exercise training programs in solid organ recipients against standard care. MEDLINE, EMBASE, the Transplant Library from the Centre for Evidence in Transplantation, and the Cochrane Central Register of Controlled Trials were searched to June 2012. RESULTS: In total, 15 eligible RCTs involving 643 patients (9 cardiac transplants [n=250 patients], 2 kidney transplants [n=164 patients], 3 lung transplants [n=110 patients], and 1 liver transplant [n=119 patients]) were included. Cardiac transplant recipients who engaged in an exercise program after transplantation showed significant improvement in maximal oxygen uptake (standardized mean difference, 0.77; 95% confidence interval, 0.10-1.45) but no improvement in the overall serum lipid profile, blood pressure, and glycemic control compared with standard care. Among other solid organ transplant recipients, no significant improvements in exercise capacity or cardiovascular risk factors such as incidence of new-onset diabetes after transplantation were observed, but all effect estimates were very imprecise. CONCLUSIONS: Exercise training is a promising but unproven intervention for improving the cardiovascular outcomes of solid organ transplant recipients. Existing trials are small, of relatively short duration, and focused on surrogate outcomes. Large-scale RCTs are urgently required if resources are to be directed toward exercise programs.

Dieleman, S. and C. H. Roder (2013). "Emotional memory modulation in schizophrenia: an overview." Acta Psychiatr Scand 127(3): 183-94.

OBJECTIVE: In healthy controls, the emotional charge of stimuli influences how well stimuli are remembered. Although patients with schizophrenia (SCZ) have deficits in memory and in emotional processing, studies on emotional memory modulation (EMM) in SCZ report contradictory results. The aim of this review was to investigate whether methodological differences could explain these contradictory results. METHOD: We reviewed the literature to investigate whether task differences could explain these differences. Due to the methodological differences, a meta-analysis was not possible. RESULTS: Fourteen studies were identified that used a total of 22 tasks to study EMM in patients with SCZ. Two-thirds of the tasks showed no differences in EMM between patients with SCZ and healthy controls. Differences in EMM were found more often when long-term compared to short-term memory was measured, when memory instructions were implicit instead of explicit and when stronger emotional stimuli were used. An overall memory deficit or the mode of retrieval was not related to EMM. CONCLUSION: Deficits in EMM in long-term compared to short-term memory point toward impaired emotional modulation of memory consolidation. Reduced EMM on implicit, but not explicit, tasks suggests a deficit in unconsciously using emotional content to modulate memory.

Dimondi, V. P. and K. Rafferty (2013). "Review of continuous-infusion vancomycin." Ann Pharmacother 47(2): 219-27.

OBJECTIVE: To evaluate the efficacy and safety of administering vancomycin as a continuous infusion. DATA SOURCES: Literature was accessed through MEDLINE (1977-September 2012), Embase (1977-September 2012), and Google Scholar, using the terms vancomycin, continuous, discontinuous, infusion, pharmacokinetics, pharmacodynamics, and nephrotoxicity. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Studies including more than 30 adults were included in the safety and efficacy review. DATA SYNTHESIS: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) carry a significant risk of morbidity and mortality. Vancomycin is commonly prescribed for invasive MRSA infections and has been traditionally administered as an intermittent infusion. Administering vancomycin as a continuous infusion is a novel approach to improving its efficacy and safety profile. Fourteen clinical trials were reviewed (2 prospective, 1 meta-analysis, 11 retrospective). The pharmacodynamic profiles between continuous-infusion vancomycin and intermittent-infusion vancomycin were comparable. Continuous-infusion therapy did not significantly improve the efficacy of vancomycin in the treatment of invasive MRSA infections. Conflicting results exist regarding the safety profile of continuous-infusion compared with intermittent-infusion vancomycin. The only published prospective randomized clinical trial comparing continuous infusion with intermittent therapy found no significant difference in the rates of nephrotoxicity. The data from retrospective studies are heterogeneous and show variable rates of nephrotoxicity. In general, compatibility information for administering vancomycin as a continuous infusion is unavailable. CONCLUSIONS: Overall, currently available evidence is insufficient to conclude whether an improvement in vancomycin efficacy exists when it is administered as a continuous infusion. The risk of nephrotoxicity associated with continuous-infusion vancomycin requires further investigation in prospective randomized trials. Specific patient populations that would benefit from continuous-infusion vancomycin have yet to be determined.

Dimova, R. B., M. Zeremski, et al. (2013). "Determinants of Hepatitis C Virus Treatment Completion and Efficacy in Drug Users Assessed by Meta-analysis." Clin Infect Dis 56(6): 806-16.

Background. Hepatitis C virus (HCV)-infected drug users (DUs) have largely been excluded from HCV care. We conducted a systematic review and meta-analysis of the literature on treatment completion and sustained virologic response (SVR) rates in DUs. We assessed the effects of different treatment approaches and services to promote HCV care among DUs as well as demographic and viral characteristics. Methods. Studies of at least 10 DUs treated with pegylated interferon/ribavirin that reported SVR were analyzed. Heterogeneity was assessed (Cochran test) and investigated (meta-regression), and pooled rates were estimated (random effects). Results. Thirty-six studies comprising 2866 patients were retrieved. The treatment completion rate among DUs was 83.4% (95% confidence interval [CI], 77.1%-88.9%). Among studies that included addiction-treated and untreated patients during HCV therapy, the higher the proportion of addiction-treated patients, the higher the HCV treatment completion rate (P < .0001). After adjusting for human immunodeficiency virus (HIV)/HCV coinfection, sex, and treatment of addiction, support services during antiviral therapy increased treatment completion (P < .0001). The pooled SVR rate was 55.5% (95% CI, 50.6%-60.3%). Genotype 1/4 (P = .0012) and the proportion of HIV-coinfected DUs (P = .0173) influenced the SVR rate. After adjusting for HCV genotype 1/4 and HIV/HCV coinfection, the SVR rate was positively correlated with involvement of a multidisciplinary team (P < .0001). Conclusions. Treatment of addiction during HCV therapy results in higher treatment completion. Our pooled SVR rate is similar to that obtained in registration trials in the general population. Treatment of addiction during HCV therapy will likely be important for HCV-infected DUs undergoing treatment with more complex regimens including direct-acting antivirals.

Ding, F. H., Y. Li, et al. (2013). "Impact of Heart Rate on Central Hemodynamics and Stroke: A Meta-Analysis of beta-Blocker Trials." Am J Hypertens 26(1): 118-25.

BACKGROUND In a meta-analysis, we investigated effects of beta-blockers on central hemodynamic measurements and explored the impact of heart rate (HR) on central hemodynamics and the risk of stroke. METHODS We searched randomized controlled trials that compared beta-blockers with other classes of antihypertensive drugs in reducing central systolic blood pressure (cSBP) and augmentation index (cAI) and in preventing stroke. A random-effects model was used to compute pooled estimates. RESULTS In 9 trials (n = 754), beta-blockers were less efficacious in reducing cAI than all the other classes of drugs (8.6%, P < 0.001). beta-blockers were also less efficacious in reducing cSBP than angiotensin converting enzyme inhibitors (7.7mm Hg, P = 0.02) and angiotensin receptor blockers (3.6mm Hg, P = 0.005) but not the other classes of drugs (P >/= 0.50). In a meta-regression analysis of these 9 trials, the baseline-adjusted difference in HR between randomized groups was associated with cAI (7.0% increase for each 10 bpm decrease in HR, P = 0.02), which was associated with cSBP (1.2mm Hg increase for each 1% increase in cAI, P = 0.009). In 5 outcome trials, the pooled OR of stroke was 1.23 (P < 0.001), which would be accounted for by the difference in cSBP derived from the above meta-regression analysis. CONCLUSIONS Slowing HR with beta-blockers may increase cAI and in turn may decrease cSBP less than with other classes of drugs. This mechanism might account for a smaller reduction in the risk of stroke when using beta-blockers to treat hypertension.

Ding, G., W. Xu, et al. (2013). "CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis." Mol Biol Rep.

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (ORTC vs. TT = 1.33, 95 % CI 1.10-1.61, P OR = 0.004; ORCC+TC vs. TT = 1.27, 95 % CI 1.05-1.55, P OR = 0.016). Stratified analysis of high quality studies also confirmed the significant association (ORTC vs. TT = 1.32, 95 % CI 1.04-1.67, P OR = 0.024; ORCC+TC vs. TT = 1.30, 95 % CI 1.02-1.66, P OR = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (ORTC vs. TT = 1.44, 95 % CI 1.20-1.72, P OR < 0.001; ORCC+TC vs. TT = 1.33, 95 % CI 1.12-1.58, P OR = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.

Ding, H., W. Du, et al. (2013). "Silodosin is effective for treatment of LUTS in men with BPH: a systematic review." Asian J Androl 15(1): 121-8.

The aim of this study was to systematically review the evidence on the efficacy and safety of silodosin treatments on lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) from randomized controlled trials. We searched PubMed (1966-December 2011), Embase (1974-December 2011) and the Cochrane Library Database (2011, Issue 12). The assessed outcome measures were the change from baseline for the International Prostate Symptom Score (IPSS), quality of life (QoL) score, peak urine maximum flow rate (Q(max)), QoL related to urinary symptoms and adverse effects. Two authors independently assessed the study quality and extracted data. All data were analysed using RevMan 5.1. The meta-analysis included four randomized controlled trials with a total of 2504 patients. The study durations were each 12 weeks. At the follow-up end points, the pooled results showed that the change from baseline for the silodosin group was significantly higher than the placebo group for the IPSS, QoL score and Q(max)(mean difference (MD)=-2.78, P<0.00001; MD=-0.42, P=0.004; MD=1.17, P<0.00001,respectively) and patients felt more satisfied with QoL related to urinary symptoms in the silodosin group than the placebo group. Ejaculation disorder was the most commonly reported adverse effect. The pooled results also showed that the silodosin group was superior to the 0.2 mg tamsulosin group with respect to the IPSS and QoL score (IPSS: MD=-1.14, P=0.02; QoL score: MD=-0.26, P=0.02) and inferior to the 0.2 mg tamsulosin group with respect to Q(max) (MD=-0.85, P=0.01). In contrast, there was no significant difference in the incidence of ejaculation disorder and dizziness between the silodosin and 0.2 mg tamsulosin groups. The current meta-analysis suggested that silodosin is an effective therapy for LUTS in men with BPH and is not inferior to 0.2 mg tamsulosin.

Ding, H., J. Q. Yuan, et al. (2013). "Systematic review and meta-analysis of application of fibrin sealant after liver resection." Curr Med Res Opin.

Abstract Background: Fibrin sealant (FS) has been increasingly used on the raw surface after liver resection but its clinical value has not been established to date. The aim of this study was to evaluate the efficacy and safety of the employment of FS after liver resection. Methods: PubMed, Cochrane Library, Embase, CNKI, CBM and VIP were searched for randomized trials comparing the effect of FS with no FS or any other intervention for patients undergoing liver resection. Primary outcomes included time to hemostasis, hemostatic success, amount of drainage and drainage duration. Results: Eleven randomized controlled trials were included. Meta-analysis suggested that the amount of drainage (standard mean difference -0.30; 95% confidence interval [CI] -0.82 to 0.23) and drainage duration (mean difference [MD] -0.46, 95% CI -0.61 to -1.53) were similar between FS group and no FS group. Compared with topical hemostatic agents, FS could significantly reduce time to hemostasis (MD -208.46, 95% CI -228.22 to -188.70) and increase hemostasis success rate (relative risk 1.35, 95% CI 1.17 to 1.57). Two trials compared FS with argon beam coagulation (ABC), which both suggested that FS could significantly decrease the time to hemostasis. Conclusions: This study demonstrated a modest benefit of FS over no FS, topical hemostatic agents and ABC in controlling intraoperative bleeding from the raw liver surface after liver resection. But there is no evidence that FS is beneficial to patients in reducing amount of drainage and drainage duration.

Ding, J., G. Liao, et al. (2013). "The necessity of indwelling gastrointestinal decompression after gastrectomy: a meta-analysis." J Surg Res 179(1): e71-81.

BACKGROUND: This meta-analysis was designed to evaluate the necessity of indwelling gastrointestinal decompression after gastrectomy. METHODS: Medline, Embase, and the Cochrane Library were searched. We identified randomized controlled trials that compared individuals with or without gastrointestinal decompression after gastrectomy, and a meta-analysis was performed on data regarding the recovery time of gastrointestinal function, length of hospital stay, complications, and mortality using fixed effect and random effect models. RESULTS: Eight randomized controlled trials that had enrolled 975 patients were included in the present study. The difference in the interval to oral intake (weighted mean difference 0.56, 95% confidence interval [CI] 0.16-0.96, P = 0.006) between the decompression group and nondecompression group was significant, but no significant differences were found in the interval to flatus (weighted mean difference 0.24, 95% CI -0.13 to 0.61, P = 0.20) or length of hospital stay (weighted mean difference 1.04, 95% CI -0.05 to 2.14, P = 0.06). Additionally, no significant differences were found in complications, including nausea or vomiting (odds ratio [OR] 1.23, 95% CI 0.57-2.65, P = 0.59), fever (OR 1.55, 95% CI 0.96-2.51, P = 0.07), pulmonary complications (OR 1.41, 95% CI 0.82-2.43, P = 0.22), anastomotic leakage (OR 1.15, 95% CI 0.55-2.40, P = 0.70), paralytic ileus or small bowel obstruction (OR 1.80, 95% CI 0.57-5.70, P = 0.32), intra-abdominal abscess (OR 1.08, 95% CI 0.50-2.34, P = 0.84), wound infection (OR 1.29, 95% CI 0.56-2.96, P = 0.55), or wound dehiscence (OR 1.47, 95% CI 0.43-4.95, P = 0.54) between the two groups. A sensitivity analysis of the pooled data from high-quality studies and studies with >20 cases per group showed that the length of hospital stay was prolonged significantly in the decompression group compared with the nondecompression group. CONCLUSIONS: Routine gastrointestinal decompression after gastrectomy does not promote the recovery of gastrointestinal function or reduce the incidence of postoperative complications. In our series, decompression was correlated with a prolonged interval to oral intake, a longer duration of hospitalization, and increased patient discomfort.

Ding, J., G. Q. Liao, et al. (2013). "Laparoscopic versus open right hemicolectomy for colon cancer: a meta-analysis." J Laparoendosc Adv Surg Tech A 23(1): 8-16.

OBJECTIVE: This meta-analysis was designed to assess the feasibility and safety of laparoscopic right hemicolectomy for colon cancer. RESEARCH DESIGN: A systematic search of the MEDLINE, EMBASE, and Cochrane databases identified 12 studies that met the inclusion criteria for data extraction. Publications that compared laparoscopic right hemicolectomy and open right hemicolectomy for treatment of colon cancer in the past 20 years were collected for review. The primary outcomes used for meta-analysis were operating time, blood loss, number of harvested lymph nodes, time to first flatus, postoperative hospital stay, postoperative complications, mortality, and rate of recurrence. RESULTS: Twelve studies that included 1057 patients were examined. Of these patients, 475 and 582 had undergone laparoscopic right hemicolectomy and open right hemicolectomy, respectively. There were significant reductions in blood loss, time to first flatus, postoperative hospital stay, and rate of wound but a operating time for laparoscopic right hemicolectomy compared with open right hemicolectomy. Other outcome variables such as number of harvested lymph nodes, postoperative complications except wound infection, mortality, and rate of recurrence were not found to be statistically significant for either group. CONCLUSIONS: Compared with open right hemicolectomy, laparoscopic right hemicolectomy has the advantages of minimal invasion, faster recovery, and a lower rate of wound infection, and it can achieve the same degree of radicality and short-term prognosis as open right hemicolectomy. The drawback is that the operative time is longer.

Ding, J., G. Q. Liao, et al. (2013). "Medial Versus Lateral Approach in Laparoscopic Colorectal Resection: A Systematic Review and Meta-analysis." World J Surg 37(4): 863-72.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of the medial approach (MA) and the lateral approach (LA) in the treatment of colorectal disease. METHODS: Studies published since 1994 that compared MA versus LA in laparoscopic colorectal resection were collected. Data on conversion rate, operative time, blood loss, number of harvested lymph nodes, hospital stay, complications, mortality, rate of recurrence, and hospitalization costs for MA and LA were meta-analyzed using fixed-effect and random-effect models. RESULTS: Five cohort studies (2 randomized controlled trials and 3 retrospective studies) that included 881 patients were studied. Of these patients, 475 and 582 had undergone laparoscopic colorectal resection via MA and LA, respectively. There were significant reductions in conversion rate and operative time and possible reductions in blood loss and hospitalization costs for MA compared to LA; however, there were fewer harvested lymph nodes for MA compared with LA, which remains to be further studied. Other outcome variables such as postoperative complications, postoperative immune function, mortality, and rate of recurrence were not found to be statistically significant for either group. Sensitivity analysis on the pooled data from randomized controlled trials showed that the conversion rates were not significantly different between MA and LA. CONCLUSIONS: Compared with the lateral approach, the medial approach has the advantages of shorter operative time and possibly lower conversion rate; it also can be as safe as the lateral approach. Whether the MA has less blood loss and lower hospitalization costs remains to be confirmed, and its oncological safety and long-term prognosis are not clear. Due to insufficient data from a limited number of studies, inadequate assessment of the results may arise.

Ding, Q., B. Fan, et al. (2013). "Interleukin-10-819C>T polymorphism contributed to cancer risk: evidence from 29 studies." Cytokine 61(1): 139-45.

Cytokines are important modulators in the interactions between the host immune system and malignant tumor. Of these, Interleukin-10 (IL-10) is an important immunoregulatory cytokine mainly produced by macrophages and T lymphocytes. To date, a number of studies investigated the role of the IL-10-819C>T polymorphism in the aetiology of cancers of various organs. However, the results of these studies remain inconclusive. So, we carried out a meta-analysis on all eligible case-control studies to estimate the overall cancer risk of IL-10-819C>T polymorphism as well as to quantify the between-study heterogeneity and potential bias. This meta-analysis, including 8157 cases and 10473 controls from 29 published case-control studies, explored the association between a potentially functional polymorphism, -819C>T within the IL-10 promoter region and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The results provided evidence that the IL-10-819C>T polymorphism was associated with a significant decrease in overall cancer risk. In the stratified analyses, the risk remained for studies of "other cancer", smoking-related cancer, Asian populations and hospital-based studies. This meta-analysis identified an evidence of the association between the IL-10-819C>T and cancer risk, especially in "other cancer", smoking-related cancers, Asians and hospital-based studies. Further large case-control studies, especially studies in African population were needed to validate our results.

Ding, Q., Y. Shi, et al. (2013). "The Interleukin-10 Promoter Polymorphism rs1800872 (-592C>A), Contributes to Cancer Susceptibility: Meta-Analysis of 16 785 Cases and 19 713 Controls." PLoS One 8(2): e57246.

Interleukin-10 (IL-10) is a multifunctional cytokine which participates in the development and progression of various malignant tumors. To date, a number of case-control studies were conducted to detect the association between -592C>A polymorphism and cancer risk in humans. However, the results of these studies on the association remain conflicting. In an effort to solve this controversy, we performed a meta-analysis based on 70 case-control studies from 65 articles, including 16 785 cancer cases and 19 713 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results suggested that the variant homozygote genotype AA of the -592C>A polymorphism was associated with a moderately decreased risk of all cancer types (OR = 0.90, 95% CI = 0.83-0.98 for homozygote comparison, OR = 0.92, 95% CI = 0.86-0.98 for recessive model). In the stratified analyses, the risk remained for studies of smoking-related cancer, Asian populations and hospital-based studies. These results suggested that the -592C>A polymorphism might contribute to the cancer susceptibility, especially in smoking-related cancer, Asians and hospital-based studies. Further studies are needed to confirm the relationship.

Dingemann, J. and B. M. Ure (2013). "Systematic Review of Level 1 Evidence for Laparoscopic Pediatric Surgery: Do Our Procedures Comply with the Requirements of Evidence-Based Medicine?" Eur J Pediatr Surg.

Introduction Laparoscopic techniques have evolved quickly in recent years and are regarded as standard procedures in pediatric surgery today. However, most studies comparing laparoscopic operations with the corresponding open procedure do not reach a high level of evidence according to the criteria of the Oxford Centre for Evidence-Based Medicine. For evidence Level 1a, a meta-analysis (MA) of different randomized controlled trials (RCTs) is required. For evidence Level 1b, at least one RCT is required. The aim of our study was to evaluate the availability of Level 1 studies comparing laparoscopic procedures with the corresponding open operation in pediatric surgery.Materials and Methods Systematic review of clinical Level 1 studies using PubMed. All MA and RCT were identified and individually reviewed. Only studies comparing pediatric laparoscopic procedures with the corresponding open operation were included. RCTs included in MA were only individually analyzed if they focused on additional endpoints. Endpoints of the study were advantages and disadvantages of laparoscopy compared with the open operation.Results A total of 20 manuscripts met the inclusion criteria (9 MA and 11 RCT). Studies providing evidence Level 1a were identified for five types of laparoscopic procedures (laparoscopic appendectomy, inguinal hernia repair, orchidopexy, pyloromyotomy, and varicocelectomy). Studies providing evidence Level 1b were identified for two types of laparoscopic procedures (fundoplication and pyeloplasty). The advantages of laparoscopy were less wound infections, ileus and postoperative pain (appendectomy), less retching (fundoplication), lower incidence of metachronous inguinal hernia, shorter hospital stay (appendectomy, orchiopexy, and pyeloplasty), and shorter time to full feeds (pyloromyotomy).Conclusion Studies providing evidence Level 1 are only available for seven laparoscopic procedures in pediatric surgery. Effort has to be made to extend the existing Level 1 evidence and to gain high level evidence for further laparoscopic procedures.

Dinicolantonio, J. J., C. J. Lavie, et al. (2013). "Meta-analysis of carvedilol versus Beta 1 selective Beta-blockers (atenolol, bisoprolol, metoprolol, and nebivolol)." Am J Cardiol 111(5): 765-9.

Because carvedilol is a unique vasodilating beta blocker (BB) exerting antioxidant activity and pleiotropic effects, it was theorized that it may confer more potent beneficial effects on cardiovascular mortality and morbidity in acute myocardial infarction (AMI) and heart failure (HF) settings. A systematic review and meta-analysis was performed of randomized, controlled, direct-comparison trials that included adults receiving atenolol, bisoprolol, metoprolol, nebivolol, or carvedilol to evaluate the effects of carvedilol compared to other BBs on mortality, cardiovascular events, and hospital readmissions in the setting of AMI or systolic HF. Compared to beta(1)-selective BBs used in HF (8 trials, n = 4,563), carvedilol significantly reduced all-cause mortality (risk ratio 0.85, 95% confidence interval 0.78 to 0.93, p = 0.0006). In 3 trials of patients with AMI (n = 644), carvedilol significantly reduced all-cause mortality by 45% (fixed-effects model: risk ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.03, random-effects model: risk ratio 0.56, 95% confidence interval 0.26 to 1.12, p = 0.10), with no reduction in non-fatal MI (risk ratio 0.61, 95% confidence interval 0.31 to 1.22, p = 0.16). In conclusion, carvedilol, as compared against atenolol, bisoprolol, metoprolol and nebivolol in randomized direct comparison trials, significantly reduced all-cause mortality in systolic HF patients. Additionally, carvedilol significantly reduced all-cause mortality compared with beta(1)-selective BBs in AMI patients using the fixed-effects model but not using the random-effects model.

Dinicolantonio, J. J., P. D. Pasquale, et al. (2013). "Low sodium versus normal sodium diets in systolic heart failure: systematic review and meta-analysis." Heart.

Divaris, K., K. L. Monda, et al. (2013). "Exploring the genetic basis of chronic periodontitis: a genome-wide association study." Hum Mol Genet.

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 x 10-6) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28-1.73, P = 3.5 x 10-7))]; moderate CP (n = 2293)-NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24-1.59, P = 7.5 x 10-8), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52-2.65, P = 8.2 x 10-7). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 x 10-9) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.

Dobarro, D., B. E. Schreiber, et al. (2013). "Clinical characteristics, haemodynamics and treatment of pulmonary hypertension in sarcoidosis in a single centre, and meta-analysis of the published data." Am J Cardiol 111(2): 278-85.

Pulmonary hypertension (PH) in sarcoidosis is associated with bad outcomes. Although there is interest in using pulmonary vasodilators (PVs) for PH in sarcoidosis, there are few data to support their use. In this study, a retrospective review of a cohort of patients with PH and sarcoidosis was conducted, focusing on those treated with PVs, and a meta-analysis of published reports indexed in MEDLINE was performed. Twenty-four patients were found. The rate of mortality or transplantation rate was 41.2%. Median survival without transplantation was 5.3 years. More patients who died or underwent transplantation during follow-up had moderate or severe lung fibrosis (66.7% vs 15.4%), had right ventricular dysfunction (80% vs 7.7%), and were in World Health Organization class IV (66.7% vs 30.8%). Body surface areas were lower in patients with events, as was cardiac output. Mortality was not different between patients treated with PVs and those not treated (54.5% vs 38.5%, p = 0.44) despite the treated patients' having more right ventricular dysfunction and worse hemodynamics. In a Cox regression survival model, lower body surface area, right ventricular dysfunction, and the presence of moderate or severe lung fibrosis were predictors of worse outcomes, but not treatment with PVs. PV-treated patients (n = 11) showed improved 6-minute walk distances and decreased N-terminal pro-B-type natriuretic peptide levels during follow-up. There was a trend toward improvement in hemodynamic profile. Four studies plus the data from this study were included in the meta-analysis. Six-minute walk distance improved by 30.64 m after treatment. Hemodynamics improved, with a reduction in mean pulmonary arterial pressure of 8.03 mm Hg and a decrease in pulmonary vascular resistance of 4.23 Wood units. In conclusion, PH in sarcoidosis is associated with adverse outcomes, particularly when accompanied by right ventricular dysfunction and/or moderate or severe lung fibrosis. Treating selected patients can improve hemodynamics and functional parameters.

Dobson, R. and G. Giovannoni (2013). "Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis." J Neurol.

Additional autoimmune diseases in people with multiple sclerosis (MS) and their relatives have been studied many times. Studies have employed different designs, and yielded conflicting results. We performed a systematic review, and calculated overall risk of additional autoimmune diseases in people with MS and their first-degree relatives. PubMed and Web of Science were searched. Thyroid disease, diabetes, inflammatory bowel disease, psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were studied. A generic inverse variance model was used, and subgroup analysis was used to explore heterogeneity. The OR of thyroid disease was increased in both people with MS (OR 1.66; p < 0.00001) and their relatives (OR 2.38; p < 0.00001). A similar association was seen between MS and inflammatory bowel disease (OR 1.56; p < 0.0001) and psoriasis (OR 1.31; p < 0.0001), although not in relatives. There was no increase in the rate of either SLE or RA. Studies examining diabetes showed significant heterogeneity and evidence of publication bias. There is an increase in the rate of certain autoimmune diseases in people with MS and their first-degree relatives. However, this does not extend to all conditions studied. Given the nonspecific clinical presentation of thyroid disease, it should be considered in all people with MS presenting with nonspecific symptoms.

Dobson, R., G. Giovannoni, et al. (2013). "The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude." J Neurol Neurosurg Psychiatry 84(4): 427-32.

BACKGROUND: Month of birth has previously been described as a risk factor for multiple sclerosis (MS). This has been hypothesised to be related to maternal vitamin D levels during pregnancy, although conclusive evidence to support this is lacking. To date, no large studies of latitudinal variation in the month of birth effect have been performed to advance this hypothesis. METHODS: Previously published data on month of birth from 151 978 MS patients were compared to expected birth rates. A linear regression model was used to assess the relationship between latitude and observed:expected birth ratio of MS patients for each month. RESULTS: Analysis of all reported data demonstrated a significant excess of MS risk in those born in April (observed:expected 1.05, p=0.05) and reduction in risk in those born in October (0.95, p=0.04) and November (0.92 p=0.01). A conservative analysis of 78 488 patients revealed an excess MS risk in those born in April (1.07, p=0.002) and May (1.11, p=0.0006), and a reduced risk in those born in October (ratio 0.94, p=0.004) and November (0.88, p=0.0002). A significant relationship between latitude and observed:expected ratio was demonstrated in December, and borderline significant relationships in May and August. CONCLUSIONS: Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude.

Dobson, R., S. Ramagopalan, et al. (2013). "Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude." J Neurol Neurosurg Psychiatry.

BACKGROUND: Oligoclonal bands (OCBs) unique to the cerebrospinal fluid are used in the diagnosis of multiple sclerosis (MS). The precise prevalence of OCBs in MS and clinically isolated syndrome (CIS) is unknown. The influence of OCBs on clinical outcomes has not been quantified. OCB prevalence has been associated with latitude in a single study, if confirmed this would provide avenues for further study. METHODS: Using a systematic review and meta-analysis approach, the proportion of OCB-positive MS and CIS and the influence of OCBs on clinical outcomes were calculated. The relationship between latitude and OCB prevalence was calculated using linear regression. RESULTS: Seventy-one articles were included. Overall, 87.7% of 12 253 MS and 68.6% of 2685 CIS patients were OCB positive. OCB-positive MS patients had an OR of 1.96 of reaching disability outcomes, although a number of negative studies did not provide data. OCB-positive CIS patients had an OR of 9.88 of conversion to MS. Latitude predicted OCB status in MS patients (p=0.009) but not in CIS patients. CONCLUSIONS: This is the largest study of OCB prevalence in MS and CIS. OCB positivity strongly predicts conversion from CIS to MS. The relationship between latitude and OCBs is confirmed, and this finding warrants further investigation.

Dodds, C. M., R. N. Henson, et al. (2013). "Overestimation of the effects of the BDNF val66met polymorphism on episodic memory-related hippocampal function: A critique of a recent meta-analysis." Neurosci Biobehav Rev.

Doebler, P., H. Holling, et al. (2013). "Correction to doebler, holling, & bohning (2012)." Psychol Methods 18(1): 120.

Reports an error in "A mixed model approach to meta-analysis of diagnostic studies with binary test outcome" by Philipp Doebler, Heinz Holling and Dankmar Bohning (Psychological Methods, 2012[Sep], Vol 17[3], 418-436). For the article, Drs. Daming Lin of the Dalla Lana School of Public Health and George Tomlinson of Toronto General Hospital and the Dalla Lana School of Public Health noted an error in the final version of Equations 6 and 7 on page 423. Dr. Doebler, in a conversation with the Interim Editor, acknowledged the error in the printing of the equations. Dr. Doebler also checked and assured the Interim Editor that the R-code that generated the substantive results for the paper were correctly coded and are identical to the R-code that would result from the derivations suggested by Drs. Lin and Tomlinson and is provided. (The following abstract of the original article appeared in record 2012-12662-001.) We propose 2 related models for the meta-analysis of diagnostic tests. Both models are based on the bivariate normal distribution for transformed sensitivities and false-positive rates. Instead of using the logit as a transformation for these proportions, we employ the talpha family of transformations that contains the log, logit, and (approximately) the complementary log. A likelihood ratio test for the cutoff value problem is developed, and summary receiver operating characteristic (SROC) curves are discussed. Worked examples showcase the methodology. We compare the models to the hierarchical SROC model, which in contrast employs a logit transformation. Data from various meta-analyses are reanalyzed, and the reanalysis indicates a better performance of the models based on the talpha transformation. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Dogliotti, A., E. Paolasso, et al. (2013). "Novel Oral Anticoagulants in Atrial Fibrillation: A Meta-analysis of Large, Randomized, Controlled Trials vs Warfarin." Clin Cardiol 36(2): 61-7.

BACKGROUND: Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings. HYPOTHESIS: Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism. METHODS: Phase III randomized warfarin-controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all-cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel-Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed-effects (if homogenous) or random-effects models (if heterogeneous). RESULTS: In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.69-0.98; P = 0.03) and all-cause mortality (RR: 0.91; 95% CI: 0.85-0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74-0.94; P = 0.004) and all-cause mortality (RR: 0.91; 95% CI: 0.84 - 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta-analysis (drug class-outcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41-0.64; P < 0.0001). CONCLUSIONS: Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all-cause mortality. The benefit is largely due to fewer hemorrhagic strokes. Ernesto Paolasso, MD, is a national lead investigator for a clinical trial sponsored by Daiichi-Sankyo investigating a novel oral anticoagulant. Robert Giugliano, MD, SM, is a member of the TIMI Study Group, which has received research grant support from Johnson & Johnson and from Daiichi-Sankyo related to clinical trials of anticoagulants. Dr. Giugliano has received honoraria for consultation/lectures from Bristol-Myers Squibb, Daiichi-Sankyo, Johnson & Johnson, and Sanofi-Aventis. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Dold, M., M. Aigner, et al. (2013). "Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials." Int J Neuropsychopharmacol 16(3): 557-74.

Because of the high number of patients with obsessive-compulsive disorder (OCD) not responding satisfactorily to initial monotherapy with serotonin reuptake inhibitors (SRIs), the evaluation of additional treatment options is highly relevant. To examine efficacy of add-on pharmacotherapy with antipsychotics, a systematic literature search was applied to identify all double-blind, randomized, placebo-controlled trials (DB-PC-RCTs) determining the efficacy of antipsychotic augmentation of SRIs in treatment-resistant OCD. The primary outcome of the pooled meta-analytic data analysis was response to the adjunctive antipsychotic treatment measured by both the rates of participants achieving response [defined as 35% reduction in Yale-Brown Obsessive-Compulsive Scale (YBOCS)] and mean changes in YBOCS total score. Twelve DB-PC-RCTs investigating quetiapine (N = 5), risperidone (N = 3), olanzapine (N = 2), aripiprazole (N = 1) and haloperidol (N = 1) with a total of 394 subjects were included. Significantly more patients responded to augmentation with antipsychotics than with placebo [relative risk = 2.10, 95% confidence intervals (CI) 1.16-3.80]. Additionally, the mean reduction of the YBOCS total score revealed an efficacy in favour of the antipsychotic medication [standardized mean difference (SMD) = 0.54, 95% CI 0.15-0.93]. Significant efficacy was identifiable only for risperidone, but not for quetiapine and olanzapine. The results regarding aripiprazole and haloperidol were inconsistent. Overall, about one-third of SRI-resistant OCD patients benefited from an augmentation strategy with antipsychotics. Based on the favourable risk:benefit ratio, risperidone can be considered as the agent of first choice and should be preferred to quetiapine and olanzapine. Further trials, mainly with higher antipsychotic doses, are required to optimize pharmacological treatment recommendations for SRI-refractory OCD.

Dolley-Hitze, T., G. Verhoest, et al. (2013). "[Angiotensin-2 type 1 receptors (AT1R) and cancers.]." Nephrol Ther.

Recently, several meta-analysis suggested an increased risk of cancers linked to the use of antagonists of angiotensin-2 receptors or inhibitors of angiotensinogen converting enzyme. The results of epidemiological studies are conflicting. Meta-analysis as well as retrospective studies are not reliable and biased, since they have never been designed to explore any pro- or antitumoral effect. We lack of prospective studies that could take off the doubt on these drugs. Nevertheless, all experimental researches pointed out potent antitumoral properties. Indeed, direct antiproliferative and neo-angiogenic inhibition have been described on tumor cell cultures as well as on animal models. Moreover, we are convinced that the use of antagonists of angiotensin-2 receptors and inhibitors of angiotensinogen converting enzyme may be then of clinical use in the near future in association with classical antitumor drugs. In this review, we proposed to explore these data by a thorough analysis of recent literature associating epidemiological and experimental studies.

Donatsky, A. M., F. Bjerrum, et al. (2013). "Surgical techniques to minimize shoulder pain after laparoscopic cholecystectomy. A systematic review." Surg Endosc.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the treatment of choice for symptomatic cholecystolithiasis. Despite the many advantages over open surgery, many patients complain about referred pain to the shoulder during the postoperative course. The purpose of this review was to evaluate different intraoperative surgical methods to minimize shoulder pain (SP). METHODS: A search of the literature was conducted using PubMed, Excerpta Medica Database (EMBASE), and Cochrane database of systematic reviews. Eligibility criteria were: randomized clinical trials or meta-analysis evaluating intraoperative surgical methods applied to minimize incidence or severity of SP after LC. Only papers published in English were included. Data extracted were year of publication, number of participants and allocation, nonsignificant or significant effect on incidence or severity of SP. RESULTS: A total of 31 papers where included in the review. Seven, 8, and 12 papers investigated the effect of drains, abdominal wall lift (AWL), and low-pressure pneumoperitoneum respectively. Four papers investigated drain suction, active gas aspiration, low insufflation flow or N(2)O insufflation respectively. The interventions that overall showed a significant reduction on either the incidence or severity of SP were low-pressure pneumoperitoneum, low insufflation rate, and active gas aspiration. CONCLUSIONS: Drainage and AWL are not recommended to reduce SP after LC. Low-pressure pneumoperitoneum with carbon dioxide is the best documented intraoperative surgical method to minimize both the incidence and severity of SP after LC.

Donegan, S., P. Williamson, et al. (2013). "Combining individual patient data and aggregate data in mixed treatment comparison meta-analysis: Individual patient data may be beneficial if only for a subset of trials." Stat Med 32(6): 914-30.

Background Individual patient data (IPD) meta-analysis is the gold standard. Aggregate data (AD) and IPD can be combined using conventional pairwise meta-analysis when IPD cannot be obtained for all relevant studies. We extend the methodology to combine IPD and AD in a mixed treatment comparison (MTC) meta-analysis. Methods The proposed random-effects MTC models combine IPD and AD for a dichotomous outcome. We study the benefits of acquiring IPD for a subset of trials when assessing the underlying consistency assumption by including treatment-by-covariate interactions in the model. We describe three different model specifications that make increasingly stronger assumptions regarding the interactions. We illustrate the methodology through application to real data sets to compare drugs for treating malaria by using the outcome unadjusted treatment success at day 28. We compare results from AD alone, IPD alone and all data. Results When IPD contributed (i.e. either using IPD alone or combining IPD and AD), the chains converged, and we identified statistically significant regression coefficients for the interactions. Using IPD alone, we were able to compare only three of the six treatments of interest. When models were fitted to AD, the treatment effects and regression coefficients for the interactions were far more imprecise, and the chains did not converge. Conclusions The models combining IPD and AD encapsulated all available evidence. When exploring interactions, it can be beneficial to obtain IPD for a subset of trials and to combine IPD with additional AD. Copyright (c) 2012 John Wiley & Sons, Ltd.

Dong, L., H. Wang, et al. (2013). "Association of Chromosome 9p21 Genetic Variants with Risk of Coronary Heart Disease in the East Asian Population: a Meta-Analysis." Ann Hum Genet.

Our aim was to evaluate the effect of SNPs in the 9p21 locus on genetic susceptibility of coronary heart disease in the East Asian population. We searched PubMed, EMBASE and CNKI for publications relating to the association between SNPs within the 9p21 locus and coronary heart disease in the East Asian population. This meta-analysis was assessed by STATA 9.2. Twenty-one studies from 15 eligible papers composing 25,945 cases and 31,777 control subjects were included in the meta-analysis. The odds ratio (OR) and 95% confidence interval (CI) for the risk allele was 1.30 (1.25-1.35) with moderate heterogeneity. No publication bias was observed in this study. Sensitivity analysis further strengthened the validity of this association. In conclusion, SNPs within the 9p21 locus were strongly associated with the risk of coronary heart disease in the East Asian population with a similar risk OR to the Caucasian population.

Dong, Y. H., H. H. Lin, et al. (2013). "Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials." Thorax 68(1): 48-56.

BACKGROUND: The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD. METHODS: Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting beta2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison. RESULTS: 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model. CONCLUSION: Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.

Dongiovanni, P. and L. Valenti (2013). "Peroxisome proliferator-activated receptor genetic polymorphisms and nonalcoholic Fatty liver disease: any role in disease susceptibility?" PPAR Res 2013: 452061.

Nonalcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extend from simple steatosis, that is, increased hepatic lipid content, to nonalcoholic steatohepatitis (NASH), a condition that may progress to cirrhosis with its associated complications. Nuclear hormone receptors act as intracellular lipid sensors that coordinate genetic networks regulating lipid metabolism and energy utilization. This family of transcription factors, in particular peroxisome proliferator-activated receptors (PPARs), represents attractive drug targets for the management of NAFLD and NASH, as well as related conditions such as type 2 diabetes and the metabolic syndrome. The impact on the regulation of lipid metabolism observed for PPARs has led to the hypothesis that genetic variants within the human PPARs genes may be associated with human disease such as NAFLD, the metabolic syndrome, and/or coronary heart disease. Here we review the available evidence on the association between PPARs genetic polymorphism and the susceptibility to NAFLD and NASH, and we provide a meta-analysis of the available evidence. The impact of PPAR variants on the susceptibility to NASH in specific subgroup of patients, and in particular on the response to therapies, especially those targeting PPARs, represents promising new areas of investigation.

Dou, C., J. Zhang, et al. (2013). "The association of ACT -17 A/T polymorphism with Alzheimer's disease: a meta-analysis." Curr Alzheimer Res 10(1): 63-71.

Association studies between Alpha-1-antichymotrypsin (ACT)-17(A > T) polymorphisms and Alzheimer's disease (AD) susceptibility have shown conflicting results. In this investigation, we performed a meta-analysis to assess the purported associations. Subgroup analyses based on ethnicity (Caucasians, East-Asian and American mixed) were also performed including a total of 5,676 AD patients and 5,460 controls for ACT-17. Overall, allele contrast (A vs. T) of ACT -17 polymorphism produced significant results in the worldwide population [P(heterogeneity)=0.01, random-effects (RE) odds ratio (OR) 1.12; 95% CI 1.04-1.21, P=0.003] and in the Caucasian population [P(heterogeneity)=0.03, RE OR1.11 95% CI 1.01-1.24, P=0.04]. Meta-analyses of other genetic contrasts suggested that the A allele carriers are associated with increased susceptibility to AD in variant populations. No significant association was observed in the East-Asian subgroup analysis. In conclusion, ACT-17 variation presents a risk factor for AD in the worldwide population, especially in the Caucasian population.

Dougan, B. K., M. S. Horswill, et al. (2013). "Athletes' Age, Sex, and Years of Education Moderate the Acute Neuropsychological Impact of Sports-Related Concussion: A Meta-analysis." J Int Neuropsychol Soc: 1-17.

The objective of this study is to determine which pre-existing athlete characteristics, if any, are associated with greater deficits in functioning following sports-related concussion, after controlling for factors previously shown to moderate this effect (e.g., time since injury). Ninety-one independent samples of concussion were included in a fixed+systematic effects meta-analysis (n = 3,801 concussed athletes; 5,631 controls). Moderating variables were assessed using analogue-to-ANOVA and meta-regression analyses. Post-injury assessments first conducted 1-10 days following sports-related concussion revealed significant neuropsychological dysfunction, postural instability and post-concussion symptom reporting (d = -0.54, -1.10, and -1.14, respectively). During this interval, females (d = -0.87), adolescent athletes competing in high school competitions (d = -0.60), and those with 10 years of education (d = -1.32) demonstrated larger post-concussion neuropsychological deficits than males (d = -0.42), adults (d = -0.25), athletes competing at other levels of competition (d = -0.43 to -0.41), or those with 16 years of education (d = -0.15), respectively. However, these sub-groups' differential impairment/recovery beyond 10 days could not be reliably quantified from available literature. Pre-existing athlete characteristics, particularly age, sex and education, were demonstrated to be significant modifiers of neuropsychological outcomes within 10 days of a sports-related concussion. Implications for return-to-play decision-making and future research directions are discussed. (JINS, 2013, 19, 1-17).

Dowell, D. and R. D. Kirkcaldy (2013). "Effectiveness of gentamicin for gonorrhoea treatment: systematic review and meta-analysis." Postgrad Med J 89(1049): 142-7.

OBJECTIVES: The development of resistance to multiple antimicrobial agents has limited treatment options for gonorrhoea. The potential emergence of cephalosporin resistance in Neisseria gonorrhoeae and cephalosporin allergy in some patients make it necessary to evaluate the effectiveness of other available antimicrobial agents. Gentamicin is widely available in the USA and is used for gonorrhoea treatment in several countries. We conducted a systematic review of the medical literature to assess the effectiveness of gentamicin for treatment of uncomplicated urogenital gonococcal infections. METHODS: Two reviewers assessed relevant articles and independently selected studies that met prespecified selection criteria (including systematic enrolment and assignment to treatment and culture-confirmed diagnosis and outcome). Summary measures for selected studies were pooled using inverse variance-weighted averages with fixed effects. Heterogeneity was assessed using I(2), which estimates proportion (0-100%) of variability attributable to heterogeneity between studies. Pooled percentage with negative follow-up culture was compared with Centers for Disease Control and Prevention (CDC) criteria for selection of recommended therapy (lower 95% CI of efficacy >/=95%). RESULTS: Twenty-nine potentially relevant studies were identified; three met inclusion criteria. Two studies used 240 mg intramuscular gentamicin and one used 280 mg. Percentages with negative culture after single-dose treatment were 90.7% (n=86), 91.4% (n=220) and 95.0% (n=40). Pooled percentage with negative culture after single-dose treatment was 91.5% (95% CI 88.1% to 94.0%, I(2)=0%). CONCLUSIONS: Gentamicin does not meet current CDC criteria for recommended treatment of gonorrhoea. However, if cephalosporin resistance emerges, gentamicin may be a useful alternative agent. Evaluation of additional regimens, including combination therapy, is warranted.

Downie, L., R. Armiento, et al. (2013). "Community-acquired neonatal and infant sepsis in developing countries: efficacy of WHO's currently recommended antibiotics--systematic review and meta-analysis." Arch Dis Child 98(2): 146-54.

OBJECTIVE: To review the aetiology and antibiotic resistance patterns of community-acquired sepsis in developing countries in infants where no clear focus of infection is clinically identified. To estimate the likely efficacy of WHO's recommended treatment for infant sepsis. DESIGN: A systematic review of the literature describing the aetiology of community-acquired neonatal and infant sepsis in developing countries. Using meta-analytical methods, susceptibility was determined to the antibiotic combinations recommended by WHO: (1) benzylpenicillin/ampicillin and gentamicin, (2) chloramphenicol and benzylpenicillin, and (3) third-generation cephalosporins. RESULTS: 19 studies were identified from 13 countries, with over 4000 blood culture isolates. Among neonates, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% (39-70%) of culture positive sepsis on weighted prevalence. In infants outside the neonatal period, the most prevalent pathogens were S aureus, E coli, Klebsiella spp., Streptococcus pneumoniae and Salmonella spp., which accounted for 59% (26-92%) of culture positive sepsis. For neonates, penicillin/gentamicin had comparable in vitro coverage to third-generation cephalosporins (57% vs. 56%). In older infants (1-12 months), in vitro susceptibility to penicillin/gentamicin, chloramphenicol/penicillin and third-generation cephalosporins was 63%, 47% and 64%, respectively. CONCLUSIONS: The high rate of community-acquired resistant sepsis-especially that caused by Klebsiella spp. and S aureus-is a serious global public health concern. In vitro susceptibility data suggest that third-generation cephalosporins are not more effective in treating sepsis than the currently recommended antibiotics, benzylpenicillin and gentamicin; however, with either regimen a significant proportion of bacteraemia is not covered. Revised recommendations for effective second-line antibiotics in neonatal and infant sepsis in developing countries are urgently needed.

Drucker, A. M., S. Wu, et al. (2013). "Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization." Eur J Haematol 90(2): 142-50.

OBJECTIVES: Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors approved for the treatment of chronic myeloid leukemia (CML). In clinical trials, they have both been reported to cause rash in a significant number of patients, but its incidence varies significantly and has not been characterized clinically or histologically. The aim of this study was to determine the incidence of rash with nilotinib and dasatinib, and to provide a clinical and histopathological description of the rash. METHODS: We conducted a meta-analysis of clinical trials evaluating nilotinib and dasatinib to determine and compare the incidence of rash with these medications. Additionally, we performed a retrospective chart review to analyze the clinical presentation and histology of patients presenting with rash. RESULTS: The incidence of all-grade (grade 1-4) rash with nilotinib was 34.3% (95% CI, 27.9-41.3), higher (P = 0.017) than with dasatinib (23.3%; 95% CI, 18.8-28.6). Similarly, the incidence of high-grade rash with nilotinib (2.6%; 95% CI, 2.1-3.4) was higher (P = 0.002) than with dasatinib (1.1%; 95% CI, 0.8-1.6). The clinical presentation often consisted of a pruritic, perifollicular hyperkeratotic, occasionally erythematous papular rash affecting most areas of the body, depending on the severity. CONCLUSIONS: Both nilotinib and dasatinib are associated with rash in a significant number of patients. Further studies to prevent and treat rash with nilotinib and dasatinib are required to improve patient quality of life, adherence with therapy and oncologic outcome.

Druyts, E., M. Dybul, et al. (2013). "Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: a systematic review and meta-analysis." AIDS 27(3): 417-25.

BACKGROUND: HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa. METHODS: We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex. RESULTS: Twenty-three cohort studies, including 216 008 participants (79 892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33-38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28-1.47)]. This was consistent across sensitivity analyses. INTERPRETATION: The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed.

Druyts, E., K. Thorlund, et al. (2013). "Efficacy and Safety of Pegylated Interferon Alfa-2a or Alfa-2b Plus Ribavirin for the Treatment of Chronic Hepatitis C in Children and Adolescents: A Systematic Review and Meta-analysis." Clin Infect Dis 56(7): 961-7.

Background. A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV). Methods. Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition. Results. Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment. Conclusions. The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.

Du, B., S. Liu, et al. (2013). "Association between glucose transporter 1 rs841853 polymorphism and type 2 diabetes mellitus risk may be population specific." J Diabetes.

OBJECTIVE: So far, studies on the association between glucose transporter 1 (GLUT1) rs841853 polymorphism and type 2 diabetes mellitus (T2DM) risk have generated considerable controversy. The current study was performed to clarify the association of this genetic variation and T2DM. METHODS: A comprehensive literature search of electronic databases was conducted to obtain articles focused on the relationship between GLUT1 rs841853 polymorphism and T2DM, followed by a systemic meta-analysis. RESULTS: Fourteen articles and nineteen individual studies were included finally. Main analyses revealed extreme heterogeneity and random effect pooled ORs were weakly significant in allele contrast [OR=1.28, CI (1.01, 1.63), p=0.04] and dominant model [OR=1.52, CI (1.19, 1.94), p=0.0008] for allele T. Subgroup analyses for Caucasians showed marginal positive results in dominant model. However, analyses for Asians yielded obvious relationship to T2DM risk in all genetic models. Interestingly, allele T even seemed to be a protective factor for developing T2DM for Blacks in allele contrast. Sensitivity analyses did not alter materially for most comparisons and no publication bias was found in this meta-analysis. CONCLUSIONS: The results of current meta-analysis provided evidence that GLUT1 rs841853 polymorphism may confer increased susceptibility to T2DM in Asians. However, no strong evidence currently available supports the association between this genetic variation and T2DM in Caucasians, Blacks or overall population.

Du, H., X. Chen, et al. (2013). "Slow N-acetyltransferase 2 genotype contributes to anti-tuberculosis drug-induced hepatotoxicity: a meta-analysis." Mol Biol Rep.

Pathogenesis and genetic factors influencing predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) are not clear. Polymorphism at the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N-acetyltransferase type 2 (NAT2), is reported to be associated with the excess generation of toxic reactive metabolites. To date, many case-control studies have been carried out to investigate the relationship between the NAT2 polymorphisms and ATDH, but the results have been inconsistent. To investigate this inconsistency, a meta-analysis was performed. Databases including PubMed, Web of Science, EMBASE and CNKI were searched to find relevant studies. A total of 26 case-control studies, involving 1,198 cases and 2,921 controls were included. Overall, we found significant association between slow acetylator genotype of NAT2 and ATDH (OR = 3.10, 95 % CI: 2.47-3.88, P < 10(-5)). Significant results were also found in East Asians, South Asians, Brazilians and Middle Eastern when stratified by ethnicity. However, no significant associations were found for Caucasians. This meta-analysis demonstrated that the slow acetylator genotype of NAT2 is a risk factor associated with increased ATDH susceptibility, but these associations vary in different ethnic populations.

Du, K., Y. Hu, et al. (2013). "Long-term outcomes of antithymocyte globulin in patients with hematological malignancies undergoing myeloablative allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis." Clin Transplant.

Antithymocyte globulin (ATG) has shown efficacy in preventing acute GVHD (aGVHD) in allogeneic hematopoietic cell transplantation (allo-HCT), but its efficacy in chronic GVHD (cGVHD) and long-term outcomes remains controversial. We conducted a systematic review and meta-analysis to evaluate potential benefit and risk of prophylactic ATG use in myeloablative HCT. We searched Pubmed, EMBASE, Cochrane databases, and included 10 trials (two RCTs and eight retrospective) comparing ATG use vs. control with a total of 1859 patients. The median follow-ups were over two yr. Outcomes assessed included overall cGVHD, extensive cGVHD, overall survival (OS), disease-free survival, relapse, and causes of death. Our results showed ATG significantly decreased overall cGVHD (RR = 0.59; 95% CI: 0.53-0.66, p < 0.00001), extensive cGVHD (RR = 0.34; 95% CI: 0.25-0.47, p < 0.00001). Pooled results also showed ATG use was associated with a marginal increased risk of relapse (RR = 1.28; 95% CI: 1.01-1.63, p = 0.04), and a non-inferior OS (HR = 0.86; 95% CI: 0.74-1.01, p = 0.06). We conclude prophylactic use of ATG exerts a favorable effect in reducing cGVHD without survival impairment in a long term, although a higher relapse rate is a major threat.

Dubreuil, M., S. Greger, et al. (2013). "Improvement in wrist pain with ultrasound-guided glucocorticoid injections: A meta-analysis of individual patient data." Semin Arthritis Rheum.

OBJECTIVES: This meta-analysis compares change in wrist pain following ultrasound-guided (US-guided) intra-articular glucocorticoid injections with change in pain after palpation-guided injections in persons with inflammatory arthritis or osteoarthritis. METHODS: Data sources included MEDLINE, Cochrane, BIOSIS, CINAHL, ACR/AHRP abstracts, and Studies that assessed change in wrist pain with direct comparison of US-guided and palpation-guided injections were included in the meta-analysis. Subject-level data was sought from authors of all relevant studies. Primary outcome was mean change in wrist pain from baseline to 1-6 week follow-up by visual analog scale (VAS). Mean difference in VAS was calculated for comparative studies. Secondary outcome was proportion attaining Minimal Clinically Important Improvement (MCII), defined as VAS reduction>/=20%. Odds ratios (ORs) of MCII were calculated for comparative studies. Mean differences in VAS and ORs for MCII for comparative studies were combined using fixed and random effects meta-analysis. RESULTS: Ten studies were eligible, and adequate data was available from 4 studies with direct comparison of US-guided and palpation-guided treatment arms. The difference in mean VAS reduction (US-guided minus palpation-guided) ranged from-0.2 to 1.3, with a combined estimate of 1.0 (95% CI 0.3, 1.7). OR for MCII in comparative studies ranged from 1.0 to 12.4, with a combined OR of 3.2 (95% CI 1.2, 8.5) in favor of ultrasound. CONCLUSIONS: US-guided glucocorticoid injections to the wrist result in greater reductions in pain, and greater likelihood of attaining MCII than palpation-guided injections at 1-6 weeks follow-up.

Duerden, E. G. and M. C. Albanese (2013). "Localization of pain-related brain activation: a meta-analysis of neuroimaging data." Hum Brain Mapp 34(1): 109-49.

A meta-analysis of 140 neuroimaging studies was performed using the activation-likelihood-estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus-specific likelihood of being activated.

Duffy, A., J. Wilkerson, et al. (2013). "Hemorrhagic events in hepatocellular carcinoma patients treated with antiangiogenic therapies." Hepatology 57(3): 1068-77.

The presence of cirrhosis increases the potential risk of hemorrhage for patients with hepatocellular carcinoma (HCC). We evaluated the relative risk for hemorrhage in patients with HCC treated with antiangiogenic agents. We performed a systematic review and meta-analysis of antiangiogenic studies in HCC from 1995 to 2011. For nonrandomized studies we compared bleeding risk with other HCC single-arm studies that did not include an antiangiogenic agent. To separate disease-specific factors we also performed a comparison analysis with renal cell cancer (RCC)) studies that evaluated sorafenib. Sorafenib was associated with increased bleeding risk compared to control for all grade bleeding events (odds ratio [OR] 1.77; 95% confidence interval [CI] 1.04, 3.0) but not grade 3-5 events in both HCC and RCC (OR 1.46; 95% CI 0.9, 2.36; P = 0.45). When comparing the risk of bleeding in single-arm phase 2 studies evaluating antiangiogenic agents, this risk for all events (OR 4.34; 95% CI 2.16, 8.73) was increased compared to control. Conclusion: This analysis of both randomized and nonrandomized studies evaluating an antiangiogenic agent in HCC showed that whereas the use of sorafenib was associated with an increased risk of bleeding in HCC, this was primarily for lower-grade events and similar in magnitude to the risk encountered in RCC. (HEPATOLOGY 2013).

Duffy, L., S. Gajree, et al. (2013). "Reliability (inter-rater agreement) of the Barthel Index for assessment of stroke survivors: systematic review and meta-analysis." Stroke 44(2): 462-8.

BACKGROUND AND PURPOSE: The Barthel Index (BI) is a 10-item measure of activities of daily living which is frequently used in clinical practice and as a trial outcome measure in stroke. We sought to describe the reliability (interobserver variability) of standard BI in stroke cohorts using systematic review and meta-analysis of published studies. METHODS: Two assessors independently searched various multidisciplinary electronic databases from inception to April 2012 inclusive. Inclusion criteria comprised: original research, human stroke participants, and inter-rater reliability data on equivalent methods of BI administration. Manuscripts were reviewed against prespecified inclusion criteria. Primary outcome for meta-analysis was reliability, measured by weighted kappa (kappaw). RESULTS: From 20 210 titles, 306 abstracts were reviewed, 12 studies met inclusion criteria, and 10 were included in meta-analysis (n=543 participants; range of participants in studies, 7-21). There was substantial clinical heterogeneity with respect to method of BI application; population studied and assessors. Two papers were graded high quality. Overall interobserver reliability of standard administration of the BI was excellent (kappaw, 0.93; 95% confidence interval, 0.90-0.96 random effects modeling). CONCLUSIONS: The BI has excellent inter-rater reliability for standard administration after stroke. However, included studies were modest in size, with clinical heterogeneity and variable methodological quality. Despite these limitations, standard BI seems an appropriate outcome measure for stroke trials and practice.

Duke, A. A., L. Begue, et al. (2013). "Revisiting the Serotonin-Aggression Relation in Humans: A Meta-Analysis." Psychol Bull.

The inverse relation between serotonin and human aggression is often portrayed as "reliable," "strong," and "well established" despite decades of conflicting reports and widely recognized methodological limitations. In this systematic review and meta-analysis, we evaluate the evidence for and against the serotonin deficiency hypothesis of human aggression across 4 methods of assessing serotonin: (a) cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (CSF 5-HIAA), (b) acute tryptophan depletion, (c) pharmacological challenge, and (d) endocrine challenge. Results across 175 independent samples and over 6,500 total participants were heterogeneous, but, in aggregate, revealed a small, inverse correlation between serotonin functioning and aggression, anger, and hostility (r = -.12). Pharmacological challenge studies had the largest mean weighted effect size (r = -.21), and CSF 5-HIAA studies had the smallest (r = -.06). Potential methodological and demographic moderators largely failed to account for variability in study outcomes. Notable exceptions included year of publication (effect sizes tended to diminish with time) and self- versus other-reported aggression (other-reported aggression was positively correlated to serotonin functioning). We discuss 4 possible explanations for the pattern of findings: unreliable measures, ambient correlational noise, an unidentified higher order interaction, and a selective serotonergic effect. Finally, we provide 4 recommendations for bringing much needed clarity to this important area of research: acknowledge contradictory findings and avoid selective reporting practices; focus on improving the reliability and validity of serotonin and aggression measures; test for interactions involving personality and/or environmental moderators; and revise the serotonin deficiency hypothesis to account for serotonin's functional complexity. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Dukic, V. M., D. S. Lauderdale, et al. (2013). "Epidemics of community-associated methicillin-resistant Staphylococcus aureus in the United States: a meta-analysis." PLoS One 8(1): e52722.

Staphylococcus aureus is the most frequent cause of skin and soft tissue infections in humans. Methicillin-resistant strains of S. aureus (MRSA) that emerged in the 1960s presented a relatively limited public health threat until the 1990s, when novel community-associated (CA-) MRSA strains began circulating. CA-MRSA infections are now common, resulting in serious and sometimes fatal infections in otherwise healthy people. Although some have suggested that there is an epidemic of CA-MRSA in the U.S., the origins, extent, and geographic variability of CA-MRSA infections are not known. We present a meta-analysis of published studies that included trend data from a single site or region, and derive summary epidemic curves of CA-MRSA spread over time. Our analysis reveals a dramatic increase in infections over the past two decades, with CA-MRSA strains now endemic at unprecedented levels in many US regions. This increase has not been geographically homogeneous, and appears to have occurred earlier in children than adults.

Dullemeijer, C., O. W. Souverein, et al. (2013). "Systematic review with dose-response meta-analyses between vitamin B-12 intake and European Micronutrient Recommendations Aligned's prioritized biomarkers of vitamin B-12 including randomized controlled trials and observational studies in adults and elderly persons." Am J Clin Nutr 97(2): 390-402.

BACKGROUND: Many randomized controlled trials (RCTs) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers. The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence. OBJECTIVE: We systematically reviewed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12 status and estimated dose-response relations with the use of a meta-analysis. DESIGN: This systematic review included all RCTs, prospective cohort studies, nested case-control studies, and cross-sectional studies in healthy adult populations published through January 2010 that supplied or measured dietary vitamin B-12 intake and measured vitamin B-12 status as serum or plasma vitamin B-12, methylmalonic acid (MMA), or holotranscobalamin. We calculated an intake-status regression coefficient ( ) for each individual study and calculated the overall pooled and SE ( ) by using random-effects meta-analysis on a double-log scale. RESULTS: The meta-analysis of observational studies showed a weaker slope of dose-response relations than the meta-analysis of RCTs. The pooled dose-response relation of all studies between vitamin B-12 intake and status indicated that a doubling of the vitamin B-12 intake increased vitamin B-12 concentrations by 11% (95% CI: 9.4%, 12.5%). This increase was larger for studies in elderly persons (13%) than in studies in adults (8%). The dose-response relation between vitamin B-12 intake and MMA concentrations indicated a decrease in MMA of 7% (95% CI: -10%, -4%) for every doubling of the vitamin B-12 intake. The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to seriously alter these results. CONCLUSION: The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of populations.

Duranton, F., M. E. Rodriguez-Ortiz, et al. (2013). "Vitamin D Treatment and Mortality in Chronic Kidney Disease: A Systematic Review and Meta-Analysis." Am J Nephrol 37(3): 239-248.

Background/Aims: Hypovitaminosis D has been associated with an increased cardiovascular mortality in the general population and in patients with chronic kidney disease (CKD). Still, whether prescribing vitamin D reduces the risk of mortality in renal patients remains controversial. Methods: We searched PubMed, and the Cochrane Library for long-term longitudinal studies comparing vitamin D compounds (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and synthetic derivatives) to placebo or no treatment in renal patients, and which evaluated mortality, to perform a meta-analysis. Data concerning study quality, population and effect size were extracted independently by two investigators using predefined forms. Results: Fourteen observational studies (194,932 patients) met all eligibility criteria. Most studies were performed in hemodialysis patients and all used calcitriol or synthetic analogues. In a random effects meta-analysis, receiving any vitamin D therapy significantly reduced the risk of all-cause mortality (relative risk 0.73, 95% CI 0.65-0.82). The relative risk of death was 0.72 (95% CI 0.65-0.80) after 3 years of therapy and 0.67 (95% CI 0.45-0.98) after 5 years. In meta-regression, the risk reduction was shown to be greater in patients with higher parathyroid hormone serum levels (p = 0.01). The risk of cardiovascular mortality was also significantly reduced in patients receiving any vitamin D derivative (relative risk 0.63, 95% CI 0.44-0.92). Conclusion: Therapies with 1,25-dihydroxyvitamin D and analogues are associated with reduced mortality in CKD patients, and particularly in those suffering from secondary hyperparathyroidism. These results, based on observational evidence, are supportive of prescribing vitamin D therapies to CKD patients, while respecting good practice guidelines.

Dwivedi, O. P., R. Tabassum, et al. (2013). "Strong influence of variants near MC4R on adiposity in children and adults: a cross-sectional study in Indian population." J Hum Genet 58(1): 27-32.

Common variants near melanocortin 4 receptor (MC4R) gene are shown to be associated with adiposity but have varied effects in different age groups. Among Indians, studies have shown association of these variants with obesity in adults, but their association in children is yet to be confirmed. We evaluated association of rs17782313 and rs12970134 near MC4R with adiposity and related traits in Indians including 1362 children and 4077 adults (consisting of 2049 diabetic and 2028 nondiabetic adult subjects). Both variants rs17782313 and rs12970134 showed strong association with adiposity measures (weight, body mass index and waist circumference) in children (P-range 7.6 x 10(-5)-3.8 x 10(-12)) and nominal association in nondiabetic adults (P-range 0.05-0.003). Effect sizes on adiposity measures in children (beta range 0.22-0.26 Z-score) were ~3-fold higher compared with adults (beta range 0.06-0.08). The minor alleles of both variants showed borderline association (P-range 0.08-0.04) with risk of type 2 diabetes in adults. Meta-analysis of rs12970134 in >12 000 Indian adults corroborated its association with adiposity (P</=2.2 x 10(-9)), homeostasis model assessment-estimated insulin resistance (P=4.0 x 10(-5)) and type 2 diabetes (P=0.003) with only moderate heterogeneity, suggesting similar effect on adult Indians residing in different geographical regions. In conclusion, the study demonstrates association of variants near MC4R with obesity and related traits in Indian children and adults, with higher impact during childhood.

Dwyer, R., O. A. Skrobot, et al. (2013). "Using alzgene-like approaches to investigate susceptibility genes for vascular cognitive impairment." J Alzheimers Dis 34(1): 145-54.

Vascular cognitive impairment (VCI), including vascular dementia, is the second most common dementia after Alzheimer's disease. Despite its prevalence, the genetic etiology of sporadic VCI is largely unknown. We conducted a systematic review of all published genetic association studies of forms of sporadic VCI prior to 6 July 2012. An initial pool of 229 gene association studies yielded 104 papers (72 polymorphisms from 47 genes) that met inclusion criteria for analysis. Systematic meta-analysis was conducted on 6 polymorphisms (which had 3 or more published case-control cohorts from 69 papers) in the APOE, ACT, ACE, MTHFR, PON1, and PSEN-1 genes. Associations of increased risk for VCI were found for APOE epsilon4 (1.818 (95% CI = 1.611-2.053), p < 0.001; n = 3,554 cases, n = 12,277 controls) and MTHFR rs1801133 (1.323 (95% CI = 1.061-1.650) p = 0.013); n = 659 cases, n = 981 controls). There was marginal evidence of a protective effect for APOE epsilon2 (0.885 (95% CI = 0.783-0.999), p = 0.048; n = 3,320 cases, n = 10,786 controls). This systematic study of all published genetic association studies of sporadic VCI supports MTHFR and APOE as susceptibility genes for VCI. It also shows the utility of meta-analysis as a tool to identify potential candidate genes from numerous individual small-scale studies of diseases where sample recruitment may be limited for a variety of practical reasons.

Eaton, S. (2013). "Combining data from multiple studies: An introduction to meta-analysis in paediatric surgery." J Pediatr Surg 48(2): 281-7.

Evidence-based medicine mandates that the best available evidence should be used to inform clinical decision making. Though there is a paucity of high level evidence within paediatric surgery generally, randomised controlled trials in this age group have become more frequent recently. This article reviews the statistical basis behind effective systematic reviews and meta-analysis for the practising clinician and is based on an invited lecture to the Experimental Research Club within the BAPS/EUPSA Congress, Rome, Italy, June 2012.

Eby, L. T., T. D. Allen, et al. (2013). "An interdisciplinary meta-analysis of the potential antecedents, correlates, and consequences of protege perceptions of mentoring." Psychol Bull 139(2): 441-76.

This meta-analysis summarized youth, academic, and workplace research on the potential antecedents (demographics, human capital, and relationship attributes), correlates (interaction frequency, relationship length, performance, motivation, and social capital), and consequences (attitudinal, behavioral, career-related, and health-related outcomes) of protege perceptions of instrumental support, psychosocial support, and relationship quality to the mentor or to the relationship. A total of 173 meta-analytic correlations were computed based on data from 173 samples and a combined N of 40,737. Among antecedents, positive protege perceptions were most strongly associated with greater similarity in attitudes, values, beliefs, and personality with their mentors (rho ranged from .38 to .59). Among correlates, protege perceptions of greater instrumental support (rho = .35) and relationship quality (rho = .54) were most strongly associated with social capital while protege perceptions of greater psychosocial support were most strongly associated with interaction frequency (rho = .25). Among consequences, protege perceptions of greater instrumental support (rho = .36) and relationship quality (rho = .38) were most strongly associated with situational satisfaction while protege perceptions of psychosocial support were most highly associated with sense of affiliation (rho = .41). Comparisons between academic and workplace mentoring generally revealed differences in magnitude, rather than direction, of the obtained effects. The results should be interpreted in light of the methodological limitations (primarily cross-sectional designs and single-source data) and, in some instances, a small number of primary studies. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Efficace, F., A. Cardoni, et al. (2013). "Tyrosine-kinase inhibitors and patient-reported outcomes in chronic myeloid leukemia: a systematic review." Leuk Res 37(2): 206-13.

The main objective of this systematic review is to quantify and to summarize all studies that have included health-related quality of life (HRQOL) or, any other type of patient-reported outcomes (PROs), in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Nine papers were found and none of these were published before 2003. Overall, 3290 CML patients were enrolled in the studies reviewed. Four studies reported HRQOL data on patients treated with imatinib only. The most solid data in this area indicate that CML patients receiving TKIs have a worse HRQOL profile when compared to their peers, without cancer, in the general population and interventions to improve HRQOL outcomes are thus needed. Our review revealed the paucity of evidence-based data in this area. However, HRQOL assessment in these studies emphasize the unique information provided by the patient's perspective. Urgent efforts are needed to provide solid PROs data to complement current knowledge on clinical efficacy of TKIs.

Eggebrecht, H., A. Schmermund, et al. (2013). "Emergent cardiac surgery during transcatheter aortic valve implantation (TAVI): a weighted meta-analysis of 9,251 patients from 46 studies." EuroIntervention 8(9): 1072-80.

AIMS: Transcatheter aortic valve implantation (TAVI) is a novel treatment option for high surgical risk patients with severe symptomatic aortic valve (AV) stenosis. During TAVI, some patients may require emergent cardiac surgery (ECS). However, the incidence, reasons and outcomes of those needing ECS remain unknown. METHODS AND RESULTS: We performed a search of the English medical literature using MEDLINE to identify all studies on TAVI and evaluate the incidence of ECS (i.e., within 24 hrs of TAVI) and outcomes for these patients. Forty-six studies comprising 9,251 patients undergoing transfemoral, transapical or trans-subclavian TAVI for native AV stenosis published between 01/2004 and 11/2011 were identified and included in this weighted meta-analysis. Overall, TAVI patients were old (mean=81.3+/-5.4 years) and had a high mean logistic EuroSCORE (24.4+/-5.9%). Few patients required ECS (n=102; 1.1+/-1.1%) and this was marginally higher among those undergoing transapical TAVI as compared to those undergoing transarterial TAVI (1.9+/-1.7% vs. 0.6+/-0.9%). Data on the reasons for ECS were available in 86% (88/102 patients) and 41% of these (36/88) were performed for embolisation/dislocation of the AV prosthesis, with aortic dissection (n=14), coronary obstruction (n=5), severe AV regurgitation (n=10), annular rupture (n=6), aortic injury (n=14), and myocardial injury including tamponade (n=12) constituting the rest. Mortality at 30 days was about 9-fold higher in patients who did need as compared with those patients who did not need ECS (67.1+/-37.9% vs. 7.5+/-4.0%). CONCLUSIONS: Reported rates of ECS during TAVI were low with embolisation or dislocation of the prosthesis being the most common cause. ECS was associated with grave prognosis with two out of three patients dying by 30 days. Thus, refinement in TAVI technology should not only focus on miniaturisation and improving flexibility of the delivery systems and/or devices -which may have the potential for decreasing aortic dissection, annular rupture, and tamponade- but also incorporate modifications to prevent embolisation/dislocation of the valve.

Ekers, D. M., M. S. Dawson, et al. (2013). "Dissemination of behavioural activation for depression to mental health nurses: training evaluation and benchmarked clinical outcomes." J Psychiatr Ment Health Nurs 20(2): 186-92.

ACCESSIBLE SUMMARY: * Depression is a very common condition that causes significant distress and disability to those that experience it. It results in considerable financial problems for both the individual and the society. Talking treatments are available but are limited in availability in part to the long-term training needed leading to insufficient therapist numbers. * Behavioural activation is a relatively simple treatment that appears as effective as the more complex cognitive behavioural therapy and may be suitable to train staff such as mental health nurses relatively quickly. * We found that staff found the training acceptable and useful and that they felt it was suitable for them. Results seen in a recent research trial using mental health nurses as therapists following 5 days' training appeared to show the same level of improvement in depression symptom level as seen when the treatment is delivered by more specialist staff with much longer training. * Behavioural activation may be able to be widely disseminated with minimal time and cost among staff groups like mental health nurses. This could lead to greater access to evidence-based talking therapy for people experiencing depression. ABSTRACT: Depression causes significant distress, disability and cost within the UK. Behavioural activation (BA) is an effective single-strand psychological approach which may lend itself to brief training programmes for a wide range of clinical staff. No previous research has directly examined outcomes of such dissemination. A 5-day training course for 10 primary care mental health workers aiming to increase knowledge and clinical skills in BA was evaluated using the Training Acceptability Rating Scale. Depression symptom level data collected in a randomized controlled trial using trainees were then compared to results from meta-analysis of studies using experienced therapists. BA training was highly acceptable to trainees (94.4%, SD 6%). The combined effect size of BA was unchanged by the addition of the results of this evaluation to those of studies using specialist therapists. BA offers a promising psychological intervention for depression that appears suitable for delivery by mental health nurses following brief training.

Ekwunife, O. I., C. E. Okafor, et al. (2013). "Cost-utility analysis of antihypertensive medications in Nigeria: a decision analysis." Cost Eff Resour Alloc 11(1): 2.

BACKGROUND: Many drugs are available for control of hypertension and its sequels in Nigeria but some are not affordable for majority of the populace. This serious pharmacoeconomic question has to be answered by the nation's health economists. The objective of this study was to evaluate the cost-effectiveness of drugs from 4 classes of antihypertensive medications commonly used in Nigeria in management of hypertension without compelling indication to use a particular antihypertensive drug. METHODS: The study employed decision analytic modeling. Interventions were obtained from a meta-analysis. The Markov process model calculated clinical outcomes and costs during a life cycle of 30 years of 1000 hypertensive patients stratified by 3 cardiovascular risk groups, under the alternative intervention scenarios. Quality adjusted life year (QALY) was used to quantify clinical outcome. The average cost of treatment for the 1000 patient was tracked over the Markov cycle model of the alternative interventions and results were presented in 2010 US Dollars. Probabilistic cost-effectiveness analysis was performed using Monte Carlo simulation, and results presented as cost-effectiveness acceptability frontiers. Expected value of perfect information (EVPI) and expected value of parameter perfect information (EVPPI) analyses were also conducted for the hypothetical population. RESULTS: Thiazide diuretic was the most cost-effective option across the 3 cardiovascular risk groups. Calcium channel blocker was the second best for Moderate risk and high risk with a willingness to pay of at least 2000$/QALY. The result was robust since it was insensitive to the parameters alteration. CONCLUSIONS: The result of this study showed that thiazide diuretic followed by calcium channel blocker could be a feasible strategy in order to ensure that patients in Nigeria with hypertension are better controlled.

El-Chammas, K., J. Keyes, et al. (2013). "Pharmacologic Treatment of Pediatric Headaches: A Meta-analysis." JAMA Pediatr 167(3): 250-8.

OBJECTIVE To assess the effectiveness of prophylactic headache treatment in children and adolescents. DATA SOURCES PubMed, EMBASE, Cochrane Database of Clinical Trials, and bibliography of retrieved articles through August 11, 2012. STUDY SELECTION Randomized trials of headache treatment among children and adolescents (&lt;18 years old). INTERVENTION Any placebo-controlled trial or comparisons between 2 or more active medications. MAIN OUTCOME MEASURE Number of headaches per month. RESULTS Among 21 included trials, there were 13 placebo-controlled and 10 active comparator trials (2 also included placebo). Twenty trials focused on episodic migraines and 1 on chronic daily headaches. Drugs more effective than placebo for episodic migraines (&lt;15 headaches per month) included topiramate (difference in headaches per month, -0.71; 95% CI, -1.19 to -0.24) and trazodone (-0.60; 95% CI, -1.09 to -0.11). Ineffective drugs included clonidine, flunarizine, pizotifen, propranolol, and valproate. A single trial of fluoxetine for chronic daily headaches found it ineffective. Patients given placebo experienced a significant (P = .03) decline in headaches, from 5.6 (95% CI, 4.52-6.77; Q = 8.14 [Cochran Q is a measure of the heterogeneity of the included studies]) to 2.9 headaches per month (95% CI, 1.66-4.08; Q = 4.72). Among the 10 active comparator trials, flunarizine was more effective than piracetam (difference in headaches per month, -2.20; 95% CI, -3.93 to -0.47) but no better than aspirin, dihydroergotamine, or propranolol. Propranolol was compared with valproate as well as behavioral treatment, and 2 studies compared different doses of topiramate; none of these trials showed significant differences. CONCLUSIONS Topiramate and trazodone have limited evidence supporting efficacy for episodic migraines. Placebo was effective in reducing headaches. Other commonly used drugs have no evidence supporting their use in children and adolescents. More research is needed.

Elding, H., W. Lau, et al. (2013). "Refinement in localization and identification of gene regions associated with Crohn disease." Am J Hum Genet 92(1): 107-13.

The risk of Crohn disease (CD) has a large genetic component. A recent meta-analysis of 6 genome-wide association studies reported 71 chromosomal intervals but does not account for all of the known genetic contribution. Here, we refine localization of the previously reported intervals and also identify additional CD susceptibility genes using a mapping approach that localizes causal variants based on genetic maps in linkage disequilibrium units (LDU maps). Using 2 of the 6 cohorts, 66 of the 71 previously reported loci are confirmed and more precise location estimates for these intervals are given. We identify 78 additional gene regions that pass genome-wide significance, providing strong evidence for 144 genes. Additionally, 56 nominally significant signals, but with more stringent and precise colocalization, are identified. In total, we provide evidence for 200 gene regions confirming that CD is truly multifactorial and complex in nature. Many identified genes have functions that are compatible with involvement in immune/inflammatory processes and seem to have a large effect in individuals with extra ileal as well as ileal inflammation. The precise locations and the evidence that some genes reflect phenotypic subgroups will help identify functional variants and will lead to greater insight of CD etiology.

Elliott, R. E., O. Tanweer, et al. (2013). "Impact of Starting Point and C2 Nerve Status on the Safety and Accuracy of C1 Lateral Mass Screws: Meta-Analysis and Review of the Literature." J Spinal Disord Tech.

STUDY DESIGN:: Literature review and meta-analysis. OBJECTIVE:: To compare clinical and radiographic outcomes of patients treated with C1 lateral mass screws (C1LMS), analyzing the impact of screw starting point and C2 nerve sectioning on malposition, vertebral artery injury (VAI) and C2 neuralgia and numbness. BACKGROUND:: Various starting points have been suggested for C1LMS insertion. Some advocate sectioning the C2 nerve root to ease placement. METHODS:: Online databases were searched for English-language articles between 1994 and 2012 reporting on C1LMS. Forty-two studies de