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Concept: Study heterogeneity


Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. Results We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association in Europe (1.11, 95% CI 1.00-1.22), and no association in North America (0.97, 95% CI 0.70-1.34) or Australia (0.95, 95% CI 0.70-1.29). Differences by other characteristics were small. Conclusions This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe.

Concepts: Epidemiology, Evidence-based medicine, Systematic review, Meta-analysis, Study heterogeneity, North America


This systematic review and meta-analysis was designed to investigate whether maternal psychological stress and recent life events are associated with an increased risk of miscarriage. A literature search was conducted to identify studies reporting miscarriage in women with and without history of exposure to psychological stress (the only exposure considered). The search produced 1978 studies; 8 studies were suitable for analysis. A meta-analysis was performed using a random-effects model with effect sizes weighted by the sampling variance. The risk of miscarriage was significantly higher in women with a history of exposure to psychological stress (OR 1.42, 95% CI 1.19-1.70). These findings remained after controlling for study type (cohort and nested case-control study OR 1.33 95% CI 1.14-1.54), exposure types (work stress OR 1.27, 95% CI 1.10-1.47), types of controls included (live birth OR 2.82 95% CI: 1.64-4.86). We found no evidence that publication bias or study heterogeneity significantly influenced the results. Our finding provides the most robust evidence to date, that prior psychological stress is harmful to women in early pregnancy.

Concepts: Experimental design, Epidemiology, Evidence-based medicine, Systematic review, Effect size, Meta-analysis, Study heterogeneity, Type


Over the last century, sporadic research has suggested that people whose hand, eye, foot, or ear dominances are not consistently right- or left-sided are at special risk of suffering academic difficulties. This phenomenon is known as crossed laterality. Although the bulk of this research dates from 1960’s and 1970’s, crossed laterality is becoming increasingly popular in the area of school education, driving the creation of several interventions aimed at restoring or consolidating lateral dominance. However, the available evidence is fragmentary. To determine the impact of crossed laterality on academic achievement and intelligence, we conducted a systematic review and meta-analysis of articles published since 1900. The inclusion criteria for the review required that studies used one or more lateral preference tasks for at least two specific parts of the body; they included a valid measure of crossed laterality; they measured the impact of crossed laterality on academic achievement or intelligence; and they included participants between 3 and 17 years old. The final sample included 26 articles that covered a total population of 3578 children aged 5 to 12. Taken collectively, the results of these studies do not support the claim that there is a reliable association between crossed laterality and either academic achievement or intelligence. Along with this, we detected important shortcomings in the literature, such as considerable heterogeneity among the variables used to measure laterality and among the tasks utilized to measure the outcomes. The educational implications of these results are discussed.

Concepts: Evidence-based medicine, Systematic review, Measurement, Educational psychology, The Final, Meta-analysis, Study heterogeneity, Systems of measurement


The aims were to (1) estimate the prevalence of alcohol and drug use disorders in prisoners on reception to prison, and (2) estimate and test sources of between study heterogeneity METHODS: Studies reporting the 12 month prevalence of alcohol and drug use disorders in prisoners on reception to prison from 1 January 1966 to 11 August 2015 were identified from 7 bibliographic indexes. Primary studies involving clinical interviews or validated instruments leading to DSM or ICD diagnoses were included; self-report surveys and investigations that assessed individuals more than 3 months after arrival to prison were not. Random-effects meta-analysis, and subgroup and meta-regression analyses were conducted. PRISMA guidelines were followed.

Concepts: Systematic review, Drug addiction, Meta-analysis, Study heterogeneity, Primary school, Prison, Analysis, 1966


Heterogeneity has a key role in meta-analysis methods and can greatly affect conclusions. However, true levels of heterogeneity are unknown and often researchers assume homogeneity. We aim to: a) investigate the prevalence of unobserved heterogeneity and the validity of the assumption of homogeneity; b) assess the performance of various meta-analysis methods; c) apply the findings to published meta-analyses.

Concepts: Evidence-based medicine, Systematic review, Cochrane Library, Educational psychology, Meta-analysis, Study heterogeneity


Complex or heterogeneous data pose challenges for systematic review and meta-analysis. In recent years, a number of new methods have been developed to meet these challenges. This qualitative interview study aimed to understand researchers' understanding of complexity and heterogeneity and the factors which may influence the choices researchers make in synthesising complex data.

Concepts: Scientific method, Research methods, Knowledge, Study heterogeneity



Studies have reported inconsistent results concerning the association of cesarean section with offspring obesity. We performed a systematic review and meta-analysis to examine whether cesarean section increases the risk of later overweight and obesity. Pubmed, Embase and Web of Science were searched using different combinations of two groups of keywords: ‘cesarean’ and ‘overweight/obesity’. Cohort or case-control studies that reported the association of cesarean section with childhood (3-8 years), adolescence (9-18 years) and/or adult (>19 years) overweight/obesity were eligible. Where possible, adjusted risk estimates were pooled using a random effects model; otherwise unadjusted estimates were pooled. Statistical heterogeneity was assessed with I(2) statistics; the values of 25%, 50% and 75% were considered to indicate low, medium and high heterogeneity, respectively. We conducted a subgroup analysis to identify the sources of heterogeneity according to study quality defined on the basis of the Newcastle-Ottawa Scale. In total, two case-control and seven cohort studies were identified for the literature review and 15 separate risk estimates were included in the meta-analysis. The overall pooled odds ratio (OR) of overweight/obesity for offspring delivered by cesarean section compared with those born vaginally was 1.33 (95% confidence interval (CI) 1.19, 1.48; I(2)=63%); the OR was 1.32 (1.15, 1.51) for children, 1.24 (1.00, 1.54) for adolescents and 1.50 (1.02, 2.20) for adults. In subgroup analysis, the overall pooled OR was 1.18 (1.09, 1.27; I(2)=29%) for high-quality studies and 1.78 (1.43, 2.22; I(2)=24%) for medium-quality (P for interaction=0.0005); no low-quality studies were identified. The ORs for children, adolescents and adults all tended to be lower for high-quality studies compared with medium-quality studies. Our results indicated that cesarean section was moderately associated with offspring overweight and obesity. This finding has public health implications, given the increase in cesarean births in many countries.International Journal of Obesity advance online publication, 4 December 2012; doi:10.1038/ijo.2012.195.

Concepts: Childbirth, Experimental design, Epidemiology, Meta-analysis, Study design, Study heterogeneity, Caesarean section, Random effects model


Improved preferred gait speed in older adults is associated with increased survival rates. There are inconsistent findings in clinical trials regarding effects of exercise on preferred gait speed, and heterogeneity in interventions in the current reviews and meta-analyses.

Concepts: Epidemiology, Medical statistics, Effectiveness,, Evaluation methods, Publication bias, Study heterogeneity


Abstract Background: Previous reports showed a high prevalence of obesity, diabetes, hypertension, and dyslipidemia among people suffering from posttraumatic stress disorder (PTSD). However, there is a lack of reviews that systematically analyze the relationship between PTSD and metabolic syndrome. We conducted a systematic review and meta-analysis aimed at estimating the association between PTSD and metabolic syndrome. Methods: We systematically searched PubMed, Embase, and Web of Science. We included observational studies assessing the prevalence of metabolic syndrome in a sample with PTSD and in a comparison group without PTSD. Data were analyzed using Review manager 5.1. Odds ratios (OR) with 95% confidence intervals were used as an association measure for pooled analysis, based on a random-effects model. Results: Six articles were eligible according to the inclusion criteria, for an overall number of 528 individuals suffering from PTSD and 846 controls without PTSD. The pooled OR for metabolic syndrome for people with PTSD was 1.37 (1.03-1.82). Statistical heterogeneity between the included studies was low (I(2)=22%). Conclusions: Despite some limitations, the findings of this systematic review and meta-analysis confirmed our hypothesis that individuals suffering from PTSD have a greater risk of metabolic syndrome. The potential role of unknown factors or mediators that might clarify the nature of this association needs further research.

Concepts: Scientific method, Nutrition, Cortisol, Metabolic syndrome, Complex post-traumatic stress disorder, Posttraumatic stress disorder, Stress, Study heterogeneity