Measuring Inconsistency in Meta-Analyses

MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR.
BMJ (online) (Impact Factor: 17.45). 10/2003; 327(7414):557-60. DOI: 10.1136/bmj.327.7414.557
Source: PubMed
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    • "Since advanced usage of the command can be challenging, users should utilize these outputs to ensure they are modelling the desired structure, and re-specify if necessary. Regarding setting heterogeneity levels and their interpretation, there are numerous practical guides that can prove helpful (Fletcher 2007; Higgins, Thompson, Deeks, and Altman 2003). Although we present information on data missingness mechanisms in the help file, interested users can find more details in an excellent overview provided by Horton and Kleinman (2007). "
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    ABSTRACT: Simulations are a practical and reliable approach to power calculations, especially for multi-level mixed effects models where the analytic solutions can be very complex. In addition, power calculations are model-specific and multi-level mixed effects models are defined by a plethora of parameters. In other words, model variations in this context are numerous and so are the tailored algebraic calculations. This article describes ipdpower in Stata, a new simulations-based command that calculates power for mixed effects two-level data structures. Although the command was developed having individual patient data meta-analyses and primary care databases analyses in mind, where patients are nested within studies and general practices respectively, the methods apply to any two-level structure.
    • "Sample size of each SNP was used as a weight, and the sign of the beta value was used as the direction of association of the effect allele. Evidence for the between-study heterogeneity was tested using Cochran's Q statistic and I 2 , and the P-value of the chi-square was used to declare significance [36] "
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    ABSTRACT: The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86×10(-8), OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63×10(-8), OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37×10(-9), OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52×10(-8), Pmeta=7.82×10(-9), OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.
    Molecular Genetics and Metabolism 10/2015; DOI:10.1016/j.ymgme.2015.10.008
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    • "I 2 is calculated using Q according to the following: I 2 ¼100%*(Q-degrees of freedom)/Q (Higgins et al., 2003). A value of 0% indicates no observed heterogeneity, and increasing values represent greater amounts of heterogeneity; values of 25%, 50%, and 75%, indicate low, moderate, and high levels of heterogeneity, respectively (Higgins et al., 2003). Publication bias was assessed in R (R, 2014) using funnel plots, Begg's rank test (Begg and Mazumdar, 1994) or Egger's regression tests (Egger and Smith, 1997). "
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    ABSTRACT: Background: Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. Objective: To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. Methods: We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts , extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta-analysis. Results: Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment (N=307; SMD: -0.45 (95%CI: -0.74, -0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: -0.63 (N=165; 95%CI: -1.07, -0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. Conclusion: Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety.
    Multiple Sclerosis and Related Disorders 10/2015; 5. DOI:10.1016/j.msard.2015.10.004
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