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Summary: The meta-analysis of osteoprotegerin (OPG) (TNFRSF11B) polymorphisms from genetic association studies and genome-wide association studies was performed in order to test the hypothesis of association between OPG polymorphisms and fracture. The findings showed a significant 13% to 37% protective effect of OPG on fractures in postmenopausal women (PSM) (rs2073618), overall, ≥ 60y and Western subjects (rs3134069 and rs3134070). Purpose: Fractures in older people usually result from compromised bone integrity. The multifactorial aetiology of fractures includes both genetic and environmental factors. Inconsistency of reported associations of osteoprotegerin (OPG) (TNFRSF11B) polymorphisms with fracture in the older adult population warranted a meta-analysis to determine more precise estimates. Methods: We searched for all available literature on OPG (TNFRSF11B) and fracture. Four polymorphisms were examined, one exonic (rs2073618) and three intronic (rs3134069, rs3134070 and rs3102735). The first two intron polymorphisms were combined (OPGI: osteoprotegerin intron) on account of complete linkage disequilibrium. Risks were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using the allele-genotype model that included variant (var), wild-type (wt) and heterozygote (het). Multiple comparisons were Bonferroni-corrected. We used meta-regression to examine sources of heterogeneity. Zero heterogeneity (homogeneity: I2 = 0%) and high significance (Pa < 0.00001) were the criteria for strength of evidence. Significant outcomes were subjected to sensitivity analysis and publication bias assessment. Results: From 13 articles (11 genetic association and two genome-wide), this meta-analysis generated five significant pooled ORs, all indicating reduced risks (ORs 0.44–0.87). Of the five, four highly significant comparisons (Pa ≤ 0.00001–0.002) survived the Bonferroni correction, one in rs2073618 het model of the postmenopausal women (OR 0.87, 95% CI 0.81–0.92, I2 = 0%) and the other three in OPGI wt model of the overall analysis, ≥ 60 y and Western subjects (ORs 0.63–0.71, 95% CI 0.47–0.86, I2 = 97–99%). These findings were consistent, had high significance and high statistical power and were robust and without evidence of publication bias. Four covariates (year of publication, study quality, fracture type/site and sample size) were the sources of heterogeneity in the OPGI overall outcomes (Pa = 0.0001–0.03). Conclusion: Evidence showed that the OPG (TNFRSF11B) polymorphisms reduced the risk for fracture in older adults, particularly protective among postmenopausal women, ≥ 60 y and Western subjects. [ABSTRACT FROM AUTHOR]

Background:Although early reports have suggested an association between circumcision and prostate cancer (PCa) development, results of subsequent epidemiological studies have been conflicting. Here we examine published articles that explore this association.Methods:We searched MEDLINE through PubMed and Embase for articles reporting on the association between PCa and circumcision, and performed a meta-analysis of qualifying studies.Results:On the basis of seven reports of case-control studies published from 1971 to 2014, overall findings showed nonsignificant reduced risk (odds ratio (OR) 0.88, P=0.19) of PCa in circumcised men compared with uncircumcised men, obtained under heterogeneous conditions (I2=65%). Heterogeneity and nonsignificance were erased when the overall effect was subjected to outlier treatment and three studies omitted (OR 0.90, P=0.04, I2=0%). Furthermore, subgroup analysis showed significantly reduced risks in the following subgroups: (i) post-PSA testing publications (OR 0.88, P=0.01), (ii) population-based studies (OR 0.84, P=0.05), (iii) studies that collected data by personal interview (OR 0.83, P=0.03) and (iv) studies in black race (OR 0.59, P=0.02). The strengths of these summary effects lie in the robustness revealed by sensitivity analysis.Conclusions:Stability of the reduced risks observed in key subgroups suggests that the protective feature of circumcision status against PCa is best seen in the context of the post-PSA testing and population-based studies as well as in the black race subgroup. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to evaluate the association of enteroaggregative Escherichia coli (EAEC) with acute diarrhea in children of South Asian populations. Our meta-analysis included 18 studies published between 1989 and 2011. The odds ratio (OR) was used to evaluate all available observational epidemiology studies. Modifying effects on the overall OR were approached with outlier, subgroup, cumulative, and cumulative recursive analyses. Synthesis of the 18 observational studies revealed an association between EAEC carriage and acute diarrhea, with an overall OR of 1.51, which was significant ( p = 0.008), heterogeneous (P < 0.0001), and unaffected by outlier analysis. This analysis, however, affected the subgroups by eliminating the following: (i) heterogeneity (from P < 0.0001 to 0.30-0.72) of pooled ORs in the underpowered (OR 1.37, p = 0.15), Indian (OR 1.92, p = 0.09), and hospital-based (OR 1.66, p = 0.06) studies; (ii) non-significance of these three subgroups (OR 1.56-2.01, p < 0.0001-0.003); (iii) significance of the high-powered studies (from OR 1.70, p = 0.02 to OR 1.15, p = 0.28); (iv) heterogeneity (from P < 0.0001-0.0002 to 0.11-0.15) of pooled ORs in period three (OR 1.85, p = 0.14), population-based (OR 1.36, p = 0.09), and pCVD432 (OR 1.53, p = 0.07) studies. In general, outlier treatment increased precision with the narrowing of confidence intervals, overall, and in the subgroups. Cumulative meta-analysis generally resulted in increases in the frequencies of significant effects and of heterogeneity. This meta-analysis on observational studies suggests that the association between EAEC and acute diarrhea in children is that of increased risk. This effect generally comes from heterogeneous studies of South Asian populations, but is modified with outlier and subgroup treatments. [ABSTRACT FROM AUTHOR]