One step versus two step approach for gestational diabetes screening: systematic review and meta-analysis of the randomized trials.

PubMed

Saccone, Gabriele; Caissutti, Claudia; Khalifeh, Adeeb; Meltzer, Sara; Scifres, Christina; Simhan, Hyagriv N; Kelekci, Sefa; Sevket, Osman; Berghella, Vincenzo

2017-12-03

To compare both the prevalence of gestational diabetes mellitus (GDM) as well as maternal and neonatal outcomes by either the one-step or the two-step approaches. Electronic databases were searched from their inception until June 2017. We included all randomized controlled trials (RCTs) comparing the one-step with the two-step approaches for the screening and diagnosis of GDM. The primary outcome was the incidence of GDM. Three RCTs (n = 2333 participants) were included in the meta-analysis. 910 were randomized to the one step approach (75 g, 2 hrs), and 1423 to the two step approach. No significant difference in the incidence of GDM was found comparing the one step versus the two step approaches (8.4 versus 4.3%; relative risk (RR) 1.64, 95%CI 0.77-3.48). Women screened with the one step approach had a significantly lower risk of preterm birth (PTB) (3.7 versus 7.6%; RR 0.49, 95%CI 0.27-0.88), cesarean delivery (16.3 versus 22.0%; RR 0.74, 95%CI 0.56-0.99), macrosomia (2.9 versus 6.9%; RR 0.43, 95%CI 0.22-0.82), neonatal hypoglycemia (1.7 versus 4.5%; RR 0.38, 95%CI 0.16-0.90), and admission to neonatal intensive care unit (NICU) (4.4 versus 9.0%; RR 0.49, 95%CI 0.29-0.84), compared to those randomized to screening with the two step approach. The one and the two step approaches were not associated with a significant difference in the incidence of GDM. However, the one step approach was associated with better maternal and perinatal outcomes.

Network meta-analysis: application and practice using Stata

PubMed Central

2017-01-01

This review aimed to arrange the concepts of a network meta-analysis (NMA) and to demonstrate the analytical process of NMA using Stata software under frequentist framework. The NMA tries to synthesize evidences for a decision making by evaluating the comparative effectiveness of more than two alternative interventions for the same condition. Before conducting a NMA, 3 major assumptions—similarity, transitivity, and consistency—should be checked. The statistical analysis consists of 5 steps. The first step is to draw a network geometry to provide an overview of the network relationship. The second step checks the assumption of consistency. The third step is to make the network forest plot or interval plot in order to illustrate the summary size of comparative effectiveness among various interventions. The fourth step calculates cumulative rankings for identifying superiority among interventions. The last step evaluates publication bias or effect modifiers for a valid inference from results. The synthesized evidences through five steps would be very useful to evidence-based decision-making in healthcare. Thus, NMA should be activated in order to guarantee the quality of healthcare system. PMID:29092392

Network meta-analysis: application and practice using Stata.

PubMed

Shim, Sungryul; Yoon, Byung-Ho; Shin, In-Soo; Bae, Jong-Myon

2017-01-01

This review aimed to arrange the concepts of a network meta-analysis (NMA) and to demonstrate the analytical process of NMA using Stata software under frequentist framework. The NMA tries to synthesize evidences for a decision making by evaluating the comparative effectiveness of more than two alternative interventions for the same condition. Before conducting a NMA, 3 major assumptions-similarity, transitivity, and consistency-should be checked. The statistical analysis consists of 5 steps. The first step is to draw a network geometry to provide an overview of the network relationship. The second step checks the assumption of consistency. The third step is to make the network forest plot or interval plot in order to illustrate the summary size of comparative effectiveness among various interventions. The fourth step calculates cumulative rankings for identifying superiority among interventions. The last step evaluates publication bias or effect modifiers for a valid inference from results. The synthesized evidences through five steps would be very useful to evidence-based decision-making in healthcare. Thus, NMA should be activated in order to guarantee the quality of healthcare system.

Knowledge synthesis methods for generating or refining theory: a scoping review reveals that little guidance is available.

PubMed

Tricco, Andrea C; Antony, Jesmin; Soobiah, Charlene; Kastner, Monika; Cogo, Elise; MacDonald, Heather; D'Souza, Jennifer; Hui, Wing; Straus, Sharon E

2016-05-01

To describe and compare, through a scoping review, emerging knowledge synthesis methods for generating and refining theory, in terms of expertise required, similarities, differences, strengths, limitations, and steps involved in using the methods. Electronic databases (e.g., MEDLINE) were searched, and two reviewers independently selected studies and abstracted data for qualitative analysis. In total, 287 articles reporting nine knowledge synthesis methods (concept synthesis, critical interpretive synthesis, integrative review, meta-ethnography, meta-interpretation, meta-study, meta-synthesis, narrative synthesis, and realist review) were included after screening of 17,962 citations and 1,010 full-text articles. Strengths of the methods included comprehensive synthesis providing rich contextual data and suitability for identifying gaps in the literature, informing policy, aiding in clinical decisions, addressing complex research questions, and synthesizing patient preferences, beliefs, and values. However, many of the methods were highly subjective and not reproducible. For integrative review, meta-ethnography, and realist review, guidance was provided on all steps of the review process, whereas meta-synthesis had guidance on the fewest number of steps. Guidance for conducting the steps was often vague and sometimes absent. Further work is needed to provide direction on operationalizing these methods. Copyright © 2016 Elsevier Inc. All rights reserved.

MetaGenyo: a web tool for meta-analysis of genetic association studies.

PubMed

Martorell-Marugan, Jordi; Toro-Dominguez, Daniel; Alarcon-Riquelme, Marta E; Carmona-Saez, Pedro

2017-12-16

Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise. We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results. MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/ .

Using multiple group modeling to test moderators in meta-analysis.

PubMed

Schoemann, Alexander M

2016-12-01

Meta-analysis is a popular and flexible analysis that can be fit in many modeling frameworks. Two methods of fitting meta-analyses that are growing in popularity are structural equation modeling (SEM) and multilevel modeling (MLM). By using SEM or MLM to fit a meta-analysis researchers have access to powerful techniques associated with SEM and MLM. This paper details how to use one such technique, multiple group analysis, to test categorical moderators in meta-analysis. In a multiple group meta-analysis a model is fit to each level of the moderator simultaneously. By constraining parameters across groups any model parameter can be tested for equality. Using multiple groups to test for moderators is especially relevant in random-effects meta-analysis where both the mean and the between studies variance of the effect size may be compared across groups. A simulation study and the analysis of a real data set are used to illustrate multiple group modeling with both SEM and MLM. Issues related to multiple group meta-analysis and future directions for research are discussed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Multivariate meta-analysis for non-linear and other multi-parameter associations

PubMed Central

Gasparrini, A; Armstrong, B; Kenward, M G

2012-01-01

In this paper, we formalize the application of multivariate meta-analysis and meta-regression to synthesize estimates of multi-parameter associations obtained from different studies. This modelling approach extends the standard two-stage analysis used to combine results across different sub-groups or populations. The most straightforward application is for the meta-analysis of non-linear relationships, described for example by regression coefficients of splines or other functions, but the methodology easily generalizes to any setting where complex associations are described by multiple correlated parameters. The modelling framework of multivariate meta-analysis is implemented in the package mvmeta within the statistical environment R. As an illustrative example, we propose a two-stage analysis for investigating the non-linear exposure–response relationship between temperature and non-accidental mortality using time-series data from multiple cities. Multivariate meta-analysis represents a useful analytical tool for studying complex associations through a two-stage procedure. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22807043

Two new methods to fit models for network meta-analysis with random inconsistency effects.

PubMed

Law, Martin; Jackson, Dan; Turner, Rebecca; Rhodes, Kirsty; Viechtbauer, Wolfgang

2016-07-28

Meta-analysis is a valuable tool for combining evidence from multiple studies. Network meta-analysis is becoming more widely used as a means to compare multiple treatments in the same analysis. However, a network meta-analysis may exhibit inconsistency, whereby the treatment effect estimates do not agree across all trial designs, even after taking between-study heterogeneity into account. We propose two new estimation methods for network meta-analysis models with random inconsistency effects. The model we consider is an extension of the conventional random-effects model for meta-analysis to the network meta-analysis setting and allows for potential inconsistency using random inconsistency effects. Our first new estimation method uses a Bayesian framework with empirically-based prior distributions for both the heterogeneity and the inconsistency variances. We fit the model using importance sampling and thereby avoid some of the difficulties that might be associated with using Markov Chain Monte Carlo (MCMC). However, we confirm the accuracy of our importance sampling method by comparing the results to those obtained using MCMC as the gold standard. The second new estimation method we describe uses a likelihood-based approach, implemented in the metafor package, which can be used to obtain (restricted) maximum-likelihood estimates of the model parameters and profile likelihood confidence intervals of the variance components. We illustrate the application of the methods using two contrasting examples. The first uses all-cause mortality as an outcome, and shows little evidence of between-study heterogeneity or inconsistency. The second uses "ear discharge" as an outcome, and exhibits substantial between-study heterogeneity and inconsistency. Both new estimation methods give results similar to those obtained using MCMC. The extent of heterogeneity and inconsistency should be assessed and reported in any network meta-analysis. Our two new methods can be used to fit models for network meta-analysis with random inconsistency effects. They are easily implemented using the accompanying R code in the Additional file 1. Using these estimation methods, the extent of inconsistency can be assessed and reported.

Domain Definition and Search Techniques in Meta-Analyses of L2 Research (or Why 18 Meta-Analyses of Feedback Have Different Results)

ERIC Educational Resources Information Center

Plonsky, Luke; Brown, Dan

2015-01-01

Applied linguists have turned increasingly in recent years to meta-analysis as the preferred means of synthesizing quantitative research. The first step in the meta-analytic process involves defining a domain of interest. Despite its apparent simplicity, this step involves a great deal of subjectivity on the part of the meta-analyst. This article…

Systematic Review and Meta-Analysis of Studies Evaluating Diagnostic Test Accuracy: A Practical Review for Clinical Researchers-Part II. Statistical Methods of Meta-Analysis

PubMed Central

Lee, Juneyoung; Kim, Kyung Won; Choi, Sang Hyun; Huh, Jimi

2015-01-01

Meta-analysis of diagnostic test accuracy studies differs from the usual meta-analysis of therapeutic/interventional studies in that, it is required to simultaneously analyze a pair of two outcome measures such as sensitivity and specificity, instead of a single outcome. Since sensitivity and specificity are generally inversely correlated and could be affected by a threshold effect, more sophisticated statistical methods are required for the meta-analysis of diagnostic test accuracy. Hierarchical models including the bivariate model and the hierarchical summary receiver operating characteristic model are increasingly being accepted as standard methods for meta-analysis of diagnostic test accuracy studies. We provide a conceptual review of statistical methods currently used and recommended for meta-analysis of diagnostic test accuracy studies. This article could serve as a methodological reference for those who perform systematic review and meta-analysis of diagnostic test accuracy studies. PMID:26576107

Methods for calculating confidence and credible intervals for the residual between-study variance in random effects meta-regression models

PubMed Central

2014-01-01

Background Meta-regression is becoming increasingly used to model study level covariate effects. However this type of statistical analysis presents many difficulties and challenges. Here two methods for calculating confidence intervals for the magnitude of the residual between-study variance in random effects meta-regression models are developed. A further suggestion for calculating credible intervals using informative prior distributions for the residual between-study variance is presented. Methods Two recently proposed and, under the assumptions of the random effects model, exact methods for constructing confidence intervals for the between-study variance in random effects meta-analyses are extended to the meta-regression setting. The use of Generalised Cochran heterogeneity statistics is extended to the meta-regression setting and a Newton-Raphson procedure is developed to implement the Q profile method for meta-analysis and meta-regression. WinBUGS is used to implement informative priors for the residual between-study variance in the context of Bayesian meta-regressions. Results Results are obtained for two contrasting examples, where the first example involves a binary covariate and the second involves a continuous covariate. Intervals for the residual between-study variance are wide for both examples. Conclusions Statistical methods, and R computer software, are available to compute exact confidence intervals for the residual between-study variance under the random effects model for meta-regression. These frequentist methods are almost as easily implemented as their established counterparts for meta-analysis. Bayesian meta-regressions are also easily performed by analysts who are comfortable using WinBUGS. Estimates of the residual between-study variance in random effects meta-regressions should be routinely reported and accompanied by some measure of their uncertainty. Confidence and/or credible intervals are well-suited to this purpose. PMID:25196829

From pre-registration to publication: a non-technical primer for conducting a meta-analysis to synthesize correlational data

PubMed Central

Quintana, Daniel S.

2015-01-01

Meta-analysis synthesizes a body of research investigating a common research question. Outcomes from meta-analyses provide a more objective and transparent summary of a research area than traditional narrative reviews. Moreover, they are often used to support research grant applications, guide clinical practice, and direct health policy. The aim of this article is to provide a practical and non-technical guide for psychological scientists that outlines the steps involved in planning and performing a meta-analysis of correlational datasets. I provide a supplementary R script to demonstrate each analytical step described in the paper, which is readily adaptable for researchers to use for their analyses. While the worked example is the analysis of a correlational dataset, the general meta-analytic process described in this paper is applicable for all types of effect sizes. I also emphasize the importance of meta-analysis protocols and pre-registration to improve transparency and help avoid unintended duplication. An improved understanding this tool will not only help scientists to conduct their own meta-analyses but also improve their evaluation of published meta-analyses. PMID:26500598

From pre-registration to publication: a non-technical primer for conducting a meta-analysis to synthesize correlational data.

PubMed

Quintana, Daniel S

2015-01-01

Meta-analysis synthesizes a body of research investigating a common research question. Outcomes from meta-analyses provide a more objective and transparent summary of a research area than traditional narrative reviews. Moreover, they are often used to support research grant applications, guide clinical practice, and direct health policy. The aim of this article is to provide a practical and non-technical guide for psychological scientists that outlines the steps involved in planning and performing a meta-analysis of correlational datasets. I provide a supplementary R script to demonstrate each analytical step described in the paper, which is readily adaptable for researchers to use for their analyses. While the worked example is the analysis of a correlational dataset, the general meta-analytic process described in this paper is applicable for all types of effect sizes. I also emphasize the importance of meta-analysis protocols and pre-registration to improve transparency and help avoid unintended duplication. An improved understanding this tool will not only help scientists to conduct their own meta-analyses but also improve their evaluation of published meta-analyses.

Social Cognitive Predictors of College Students' Academic Performance and Persistence: A Meta-Analytic Path Analysis

ERIC Educational Resources Information Center

Brown, Steven D.; Tramayne, Selena; Hoxha, Denada; Telander, Kyle; Fan, Xiaoyan; Lent, Robert W.

2008-01-01

This study tested Social Cognitive Career Theory's (SCCT) academic performance model using a two-stage approach that combined meta-analytic and structural equation modeling methodologies. Unbiased correlations obtained from a previously published meta-analysis [Robbins, S. B., Lauver, K., Le, H., Davis, D., & Langley, R. (2004). Do psychosocial…

Deriving percentage study weights in multi-parameter meta-analysis models: with application to meta-regression, network meta-analysis and one-stage individual participant data models.

PubMed

Riley, Richard D; Ensor, Joie; Jackson, Dan; Burke, Danielle L

2017-01-01

Many meta-analysis models contain multiple parameters, for example due to multiple outcomes, multiple treatments or multiple regression coefficients. In particular, meta-regression models may contain multiple study-level covariates, and one-stage individual participant data meta-analysis models may contain multiple patient-level covariates and interactions. Here, we propose how to derive percentage study weights for such situations, in order to reveal the (otherwise hidden) contribution of each study toward the parameter estimates of interest. We assume that studies are independent, and utilise a decomposition of Fisher's information matrix to decompose the total variance matrix of parameter estimates into study-specific contributions, from which percentage weights are derived. This approach generalises how percentage weights are calculated in a traditional, single parameter meta-analysis model. Application is made to one- and two-stage individual participant data meta-analyses, meta-regression and network (multivariate) meta-analysis of multiple treatments. These reveal percentage study weights toward clinically important estimates, such as summary treatment effects and treatment-covariate interactions, and are especially useful when some studies are potential outliers or at high risk of bias. We also derive percentage study weights toward methodologically interesting measures, such as the magnitude of ecological bias (difference between within-study and across-study associations) and the amount of inconsistency (difference between direct and indirect evidence in a network meta-analysis).

Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

PubMed Central

Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

2012-01-01

Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of “injury" gene predictors that can classify lung injury samples and identify patients at risk for clinically relevant lung injury complications. PMID:23071521

A Tutorial on Conducting Meta-Analyses of Clinical Outcome Research.

ERIC Educational Resources Information Center

Robey, Randall R.; Dalebout, Susan D.

1998-01-01

The purpose of this tutorial is to enhance the familiarity and accessibility of meta-analyses in the domains of audiology and speech-language pathology for investigating questions of treatment efficacy and treatment effectiveness. Steps to conducting a meta-analysis are explained and an example of meta-analysis using published data is included.…

Using structural equation modeling for network meta-analysis.

PubMed

Tu, Yu-Kang; Wu, Yun-Chun

2017-07-14

Network meta-analysis overcomes the limitations of traditional pair-wise meta-analysis by incorporating all available evidence into a general statistical framework for simultaneous comparisons of several treatments. Currently, network meta-analyses are undertaken either within the Bayesian hierarchical linear models or frequentist generalized linear mixed models. Structural equation modeling (SEM) is a statistical method originally developed for modeling causal relations among observed and latent variables. As random effect is explicitly modeled as a latent variable in SEM, it is very flexible for analysts to specify complex random effect structure and to make linear and nonlinear constraints on parameters. The aim of this article is to show how to undertake a network meta-analysis within the statistical framework of SEM. We used an example dataset to demonstrate the standard fixed and random effect network meta-analysis models can be easily implemented in SEM. It contains results of 26 studies that directly compared three treatment groups A, B and C for prevention of first bleeding in patients with liver cirrhosis. We also showed that a new approach to network meta-analysis based on the technique of unrestricted weighted least squares (UWLS) method can also be undertaken using SEM. For both the fixed and random effect network meta-analysis, SEM yielded similar coefficients and confidence intervals to those reported in the previous literature. The point estimates of two UWLS models were identical to those in the fixed effect model but the confidence intervals were greater. This is consistent with results from the traditional pairwise meta-analyses. Comparing to UWLS model with common variance adjusted factor, UWLS model with unique variance adjusted factor has greater confidence intervals when the heterogeneity was larger in the pairwise comparison. The UWLS model with unique variance adjusted factor reflects the difference in heterogeneity within each comparison. SEM provides a very flexible framework for univariate and multivariate meta-analysis, and its potential as a powerful tool for advanced meta-analysis is still to be explored.

Improved enteral tolerance following step procedure: systematic literature review and meta-analysis.

PubMed

Fernandes, Melissa A; Usatin, Danielle; Allen, Isabel E; Rhee, Sue; Vu, Lan

2016-10-01

Surgical management of children with short bowel syndrome (SBS) changed with the introduction of the serial transverse enteroplasty procedure (STEP). We conducted a systematic review and meta-analysis using MEDLINE and SCOPUS to determine if children with SBS had improved enteral tolerance following STEP. Studies were included if information about a child's pre- and post-STEP enteral tolerance was provided. A random effects meta-analysis provided a summary estimate of the proportion of children with enteral tolerance increase following STEP. From 766 abstracts, seven case series involving 86 children were included. Mean percent tolerance of enteral nutrition improved from 35.1 to 69.5. Sixteen children had no enteral improvement following STEP. A summary estimate showed that 87 % (95 % CI 77-95 %) of children who underwent STEP had an increase in enteral tolerance. Compilation of the literature supports the belief that SBS subjects' enteral tolerance improves following STEP. Enteral nutritional tolerance is a measure of efficacy of STEP and should be presented as a primary or secondary outcome. By standardizing data collection on children undergoing STEP procedure, better determination of nutritional benefit from STEP can be ascertained.

Meta-analysis for the comparison of two diagnostic tests to a common gold standard: A generalized linear mixed model approach.

PubMed

Hoyer, Annika; Kuss, Oliver

2018-05-01

Meta-analysis of diagnostic studies is still a rapidly developing area of biostatistical research. Especially, there is an increasing interest in methods to compare different diagnostic tests to a common gold standard. Restricting to the case of two diagnostic tests, in these meta-analyses the parameters of interest are the differences of sensitivities and specificities (with their corresponding confidence intervals) between the two diagnostic tests while accounting for the various associations across single studies and between the two tests. We propose statistical models with a quadrivariate response (where sensitivity of test 1, specificity of test 1, sensitivity of test 2, and specificity of test 2 are the four responses) as a sensible approach to this task. Using a quadrivariate generalized linear mixed model naturally generalizes the common standard bivariate model of meta-analysis for a single diagnostic test. If information on several thresholds of the tests is available, the quadrivariate model can be further generalized to yield a comparison of full receiver operating characteristic (ROC) curves. We illustrate our model by an example where two screening methods for the diagnosis of type 2 diabetes are compared.

Stepping Stones Triple P-Positive Parenting Program for Children with Disability: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Tellegen, Cassandra L.; Sanders, Matthew R.

2013-01-01

This systematic review and meta-analysis evaluated the treatment effects of a behavioral family intervention, Stepping Stones Triple P (SSTP) for parents of children with disabilities. SSTP is a system of five intervention levels of increasing intensity and narrowing population reach. Twelve studies, including a total of 659 families, met…

Knowledge synthesis methods for integrating qualitative and quantitative data: a scoping review reveals poor operationalization of the methodological steps.

PubMed

Tricco, Andrea C; Antony, Jesmin; Soobiah, Charlene; Kastner, Monika; MacDonald, Heather; Cogo, Elise; Lillie, Erin; Tran, Judy; Straus, Sharon E

2016-05-01

To describe and compare, through a scoping review, emerging knowledge synthesis methods for integrating qualitative and quantitative evidence in health care, in terms of expertise required, similarities, differences, strengths, limitations, and steps involved in using the methods. Electronic databases (e.g., MEDLINE) were searched, and two reviewers independently selected studies and abstracted data for qualitative analysis. In total, 121 articles reporting seven knowledge synthesis methods (critical interpretive synthesis, integrative review, meta-narrative review, meta-summary, mixed studies review, narrative synthesis, and realist review) were included after screening of 17,962 citations and 1,010 full-text articles. Common similarities among methods related to the entire synthesis process, while common differences related to the research question and eligibility criteria. The most common strength was a comprehensive synthesis providing rich contextual data, whereas the most common weakness was a highly subjective method that was not reproducible. For critical interpretive synthesis, meta-narrative review, meta-summary, and narrative synthesis, guidance was not provided for some steps of the review process. Some of the knowledge synthesis methods provided guidance on all steps, whereas other methods were missing guidance on the synthesis process. Further work is needed to clarify these emerging knowledge synthesis methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Meta-analysis is not an exact science: Call for guidance on quantitative synthesis decisions.

PubMed

Haddaway, Neal R; Rytwinski, Trina

2018-05-01

Meta-analysis is becoming increasingly popular in the field of ecology and environmental management. It increases the effective power of analyses relative to single studies, and allows researchers to investigate effect modifiers and sources of heterogeneity that could not be easily examined within single studies. Many systematic reviewers will set out to conduct a meta-analysis as part of their synthesis, but meta-analysis requires a niche set of skills that are not widely held by the environmental research community. Each step in the process of carrying out a meta-analysis requires decisions that have both scientific and statistical implications. Reviewers are likely to be faced with a plethora of decisions over which effect size to choose, how to calculate variances, and how to build statistical models. Some of these decisions may be simple based on appropriateness of the options. At other times, reviewers must choose between equally valid approaches given the information available to them. This presents a significant problem when reviewers are attempting to conduct a reliable synthesis, such as a systematic review, where subjectivity is minimised and all decisions are documented and justified transparently. We propose three urgent, necessary developments within the evidence synthesis community. Firstly, we call on quantitative synthesis experts to improve guidance on how to prepare data for quantitative synthesis, providing explicit detail to support systematic reviewers. Secondly, we call on journal editors and evidence synthesis coordinating bodies (e.g. CEE) to ensure that quantitative synthesis methods are adequately reported in a transparent and repeatable manner in published systematic reviews. Finally, where faced with two or more broadly equally valid alternative methods or actions, reviewers should conduct multiple analyses, presenting all options, and discussing the implications of the different analytical approaches. We believe it is vital to tackle the possible subjectivity in quantitative synthesis described herein to ensure that the extensive efforts expended in producing systematic reviews and other evidence synthesis products is not wasted because of a lack of rigour or reliability in the final synthesis step. Copyright © 2018 Elsevier Ltd. All rights reserved.

A hands-on practical tutorial on performing meta-analysis with Stata.

PubMed

Chaimani, Anna; Mavridis, Dimitris; Salanti, Georgia

2014-11-01

Statistical synthesis of research findings via meta-analysis is widely used to assess the relative effectiveness of competing interventions. A series of three papers aimed at familiarising mental health scientists with the key statistical concepts and problems in meta-analysis was recently published in this journal. One paper focused on the selection and interpretation of the appropriate model to synthesise results (fixed effect or random effects model) whereas the other two papers focused on two major threats that compromise the validity of meta-analysis results, namely publication bias and missing outcome data. In this paper we provide guidance on how to undertake meta-analysis using Stata, one of the most commonly used software packages for meta-analysis. We address the three topics covered in the previous issues of the journal, focusing on their implementation in Stata using a working example from mental health research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The choice of prior distribution for a covariance matrix in multivariate meta-analysis: a simulation study.

PubMed

Hurtado Rúa, Sandra M; Mazumdar, Madhu; Strawderman, Robert L

2015-12-30

Bayesian meta-analysis is an increasingly important component of clinical research, with multivariate meta-analysis a promising tool for studies with multiple endpoints. Model assumptions, including the choice of priors, are crucial aspects of multivariate Bayesian meta-analysis (MBMA) models. In a given model, two different prior distributions can lead to different inferences about a particular parameter. A simulation study was performed in which the impact of families of prior distributions for the covariance matrix of a multivariate normal random effects MBMA model was analyzed. Inferences about effect sizes were not particularly sensitive to prior choice, but the related covariance estimates were. A few families of prior distributions with small relative biases, tight mean squared errors, and close to nominal coverage for the effect size estimates were identified. Our results demonstrate the need for sensitivity analysis and suggest some guidelines for choosing prior distributions in this class of problems. The MBMA models proposed here are illustrated in a small meta-analysis example from the periodontal field and a medium meta-analysis from the study of stroke. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Methodology Series Module 6: Systematic Reviews and Meta-analysis

PubMed Central

Setia, Maninder Singh

2016-01-01

Systematic reviews and meta-analysis have become an important of biomedical literature, and they provide the “highest level of evidence” for various clinical questions. There are a lot of studies – sometimes with contradictory conclusions – on a particular topic in literature. Hence, as a clinician, which results will you believe? What will you tell your patient? Which drug is better? A systematic review or a meta-analysis may help us answer these questions. In addition, it may also help us understand the quality of the articles in literature or the type of studies that have been conducted and published (example, randomized trials or observational studies). The first step it to identify a research question for systematic review or meta-analysis. The next step is to identify the articles that will be included in the study. This will be done by searching various databases; it is important that the researcher should search for articles in more than one database. It will also be useful to form a group of researchers and statisticians that have expertise in conducting systematic reviews and meta-analysis before initiating them. We strongly encourage the readers to register their proposed review/meta-analysis with PROSPERO. Finally, these studies should be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist. PMID:27904176

Methodology Series Module 6: Systematic Reviews and Meta-analysis.

PubMed

Setia, Maninder Singh

2016-01-01

Systematic reviews and meta-analysis have become an important of biomedical literature, and they provide the "highest level of evidence" for various clinical questions. There are a lot of studies - sometimes with contradictory conclusions - on a particular topic in literature. Hence, as a clinician, which results will you believe? What will you tell your patient? Which drug is better? A systematic review or a meta-analysis may help us answer these questions. In addition, it may also help us understand the quality of the articles in literature or the type of studies that have been conducted and published (example, randomized trials or observational studies). The first step it to identify a research question for systematic review or meta-analysis. The next step is to identify the articles that will be included in the study. This will be done by searching various databases; it is important that the researcher should search for articles in more than one database. It will also be useful to form a group of researchers and statisticians that have expertise in conducting systematic reviews and meta-analysis before initiating them. We strongly encourage the readers to register their proposed review/meta-analysis with PROSPERO. Finally, these studies should be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist.

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.

PubMed

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-08-12

To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.

Meta-analytic framework for liquid association.

PubMed

Wang, Lin; Liu, Silvia; Ding, Ying; Yuan, Shin-Sheng; Ho, Yen-Yi; Tseng, George C

2017-07-15

Although coexpression analysis via pair-wise expression correlation is popularly used to elucidate gene-gene interactions at the whole-genome scale, many complicated multi-gene regulations require more advanced detection methods. Liquid association (LA) is a powerful tool to detect the dynamic correlation of two gene variables depending on the expression level of a third variable (LA scouting gene). LA detection from single transcriptomic study, however, is often unstable and not generalizable due to cohort bias, biological variation and limited sample size. With the rapid development of microarray and NGS technology, LA analysis combining multiple gene expression studies can provide more accurate and stable results. In this article, we proposed two meta-analytic approaches for LA analysis (MetaLA and MetaMLA) to combine multiple transcriptomic studies. To compensate demanding computing, we also proposed a two-step fast screening algorithm for more efficient genome-wide screening: bootstrap filtering and sign filtering. We applied the methods to five Saccharomyces cerevisiae datasets related to environmental changes. The fast screening algorithm reduced 98% of running time. When compared with single study analysis, MetaLA and MetaMLA provided stronger detection signal and more consistent and stable results. The top triplets are highly enriched in fundamental biological processes related to environmental changes. Our method can help biologists understand underlying regulatory mechanisms under different environmental exposure or disease states. A MetaLA R package, data and code for this article are available at http://tsenglab.biostat.pitt.edu/software.htm. ctseng@pitt.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Gene Level Meta-Analysis of Quantitative Traits by Functional Linear Models.

PubMed

Fan, Ruzong; Wang, Yifan; Boehnke, Michael; Chen, Wei; Li, Yun; Ren, Haobo; Lobach, Iryna; Xiong, Momiao

2015-08-01

Meta-analysis of genetic data must account for differences among studies including study designs, markers genotyped, and covariates. The effects of genetic variants may differ from population to population, i.e., heterogeneity. Thus, meta-analysis of combining data of multiple studies is difficult. Novel statistical methods for meta-analysis are needed. In this article, functional linear models are developed for meta-analyses that connect genetic data to quantitative traits, adjusting for covariates. The models can be used to analyze rare variants, common variants, or a combination of the two. Both likelihood-ratio test (LRT) and F-distributed statistics are introduced to test association between quantitative traits and multiple variants in one genetic region. Extensive simulations are performed to evaluate empirical type I error rates and power performance of the proposed tests. The proposed LRT and F-distributed statistics control the type I error very well and have higher power than the existing methods of the meta-analysis sequence kernel association test (MetaSKAT). We analyze four blood lipid levels in data from a meta-analysis of eight European studies. The proposed methods detect more significant associations than MetaSKAT and the P-values of the proposed LRT and F-distributed statistics are usually much smaller than those of MetaSKAT. The functional linear models and related test statistics can be useful in whole-genome and whole-exome association studies. Copyright © 2015 by the Genetics Society of America.

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies

PubMed Central

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

2016-01-01

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K-means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups. PMID:27330233

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

PubMed

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

Meta-analysis of high-latitude nitrogen-addition and warming studies implies ecological mechanisms overlooked by land models

NASA Astrophysics Data System (ADS)

Bouskill, N. J.; Riley, W. J.; Tang, J. Y.

2014-12-01

Accurate representation of ecosystem processes in land models is crucial for reducing predictive uncertainty in energy and greenhouse gas feedbacks with the climate. Here we describe an observational and modeling meta-analysis approach to benchmark land models, and apply the method to the land model CLM4.5 with two versions of belowground biogeochemistry. We focused our analysis on the aboveground and belowground responses to warming and nitrogen addition in high-latitude ecosystems, and identified absent or poorly parameterized mechanisms in CLM4.5. While the two model versions predicted similar soil carbon stock trajectories following both warming and nitrogen addition, other predicted variables (e.g., belowground respiration) differed from observations in both magnitude and direction, indicating that CLM4.5 has inadequate underlying mechanisms for representing high-latitude ecosystems. On the basis of observational synthesis, we attribute the model-observation differences to missing representations of microbial dynamics, aboveground and belowground coupling, and nutrient cycling, and we use the observational meta-analysis to discuss potential approaches to improving the current models. However, we also urge caution concerning the selection of data sets and experiments for meta-analysis. For example, the concentrations of nitrogen applied in the synthesized field experiments (average = 72 kg ha-1 yr-1) are many times higher than projected soil nitrogen concentrations (from nitrogen deposition and release during mineralization), which precludes a rigorous evaluation of the model responses to likely nitrogen perturbations. Overall, we demonstrate that elucidating ecological mechanisms via meta-analysis can identify deficiencies in ecosystem models and empirical experiments.

MetaMeta: integrating metagenome analysis tools to improve taxonomic profiling.

PubMed

Piro, Vitor C; Matschkowski, Marcel; Renard, Bernhard Y

2017-08-14

Many metagenome analysis tools are presently available to classify sequences and profile environmental samples. In particular, taxonomic profiling and binning methods are commonly used for such tasks. Tools available among these two categories make use of several techniques, e.g., read mapping, k-mer alignment, and composition analysis. Variations on the construction of the corresponding reference sequence databases are also common. In addition, different tools provide good results in different datasets and configurations. All this variation creates a complicated scenario to researchers to decide which methods to use. Installation, configuration and execution can also be difficult especially when dealing with multiple datasets and tools. We propose MetaMeta: a pipeline to execute and integrate results from metagenome analysis tools. MetaMeta provides an easy workflow to run multiple tools with multiple samples, producing a single enhanced output profile for each sample. MetaMeta includes a database generation, pre-processing, execution, and integration steps, allowing easy execution and parallelization. The integration relies on the co-occurrence of organisms from different methods as the main feature to improve community profiling while accounting for differences in their databases. In a controlled case with simulated and real data, we show that the integrated profiles of MetaMeta overcome the best single profile. Using the same input data, it provides more sensitive and reliable results with the presence of each organism being supported by several methods. MetaMeta uses Snakemake and has six pre-configured tools, all available at BioConda channel for easy installation (conda install -c bioconda metameta). The MetaMeta pipeline is open-source and can be downloaded at: https://gitlab.com/rki_bioinformatics .

Combining multiple imputation and meta-analysis with individual participant data

PubMed Central

Burgess, Stephen; White, Ian R; Resche-Rigon, Matthieu; Wood, Angela M

2013-01-01

Multiple imputation is a strategy for the analysis of incomplete data such that the impact of the missingness on the power and bias of estimates is mitigated. When data from multiple studies are collated, we can propose both within-study and multilevel imputation models to impute missing data on covariates. It is not clear how to choose between imputation models or how to combine imputation and inverse-variance weighted meta-analysis methods. This is especially important as often different studies measure data on different variables, meaning that we may need to impute data on a variable which is systematically missing in a particular study. In this paper, we consider a simulation analysis of sporadically missing data in a single covariate with a linear analysis model and discuss how the results would be applicable to the case of systematically missing data. We find in this context that ensuring the congeniality of the imputation and analysis models is important to give correct standard errors and confidence intervals. For example, if the analysis model allows between-study heterogeneity of a parameter, then we should incorporate this heterogeneity into the imputation model to maintain the congeniality of the two models. In an inverse-variance weighted meta-analysis, we should impute missing data and apply Rubin's rules at the study level prior to meta-analysis, rather than meta-analyzing each of the multiple imputations and then combining the meta-analysis estimates using Rubin's rules. We illustrate the results using data from the Emerging Risk Factors Collaboration. PMID:23703895

Longevity of Self-etch Dentin Bonding Adhesives Compared to Etch-and-rinse Dentin Bonding Adhesives: A Systematic Review.

PubMed

Masarwa, Nader; Mohamed, Ahmed; Abou-Rabii, Iyad; Abu Zaghlan, Rawan; Steier, Liviu

2016-06-01

A systematic review and meta-analysis were performed to compare longevity of Self-Etch Dentin Bonding Adhesives to Etch-and-Rinse Dentin Bonding Adhesives. The following databases were searched for PubMed, MEDLINE, Web of Science, CINAHL, the Cochrane Library complemented by a manual search of the Journal of Adhesive Dentistry. The MESH keywords used were: "etch and rinse," "total etch," "self-etch," "dentin bonding agent," "bond durability," and "bond degradation." Included were in-vitro experimental studies performed on human dental tissues of sound tooth structure origin. The examined Self-Etch Bonds were of two subtypes; Two Steps and One Step Self-Etch Bonds, while Etch-and-Rinse Bonds were of two subtypes; Two Steps and Three Steps. The included studies measured micro tensile bond strength (μTBs) to evaluate bond strength and possible longevity of both types of dental adhesives at different times. The selected studies depended on water storage as the aging technique. Statistical analysis was performed for outcome measurements compared at 24 h, 3 months, 6 months and 12 months of water storage. After 24 hours (p-value = 0.051), 3 months (p-value = 0.756), 6 months (p-value=0.267), 12 months (p-value=0.785) of water storage self-etch adhesives showed lower μTBs when compared to the etch-and-rinse adhesives, but the comparisons were statistically insignificant. In this study, longevity of Dentin Bonds was related to the measured μTBs. Although Etch-and-Rinse bonds showed higher values at all times, the meta-analysis found no difference in longevity of the two types of bonds at the examined aging times. Copyright © 2016 Elsevier Inc. All rights reserved.

Meta-analysis of high-latitude nitrogen-addition and warming studies implies ecological mechanisms overlooked by land models

DOE PAGES

Bouskill, N. J.; Riley, W. J.; Tang, J. Y.

2014-12-11

Accurate representation of ecosystem processes in land models is crucial for reducing predictive uncertainty in energy and greenhouse gas feedbacks with the climate. Here we describe an observational and modeling meta-analysis approach to benchmark land models, and apply the method to the land model CLM4.5 with two versions of belowground biogeochemistry. We focused our analysis on the aboveground and belowground responses to warming and nitrogen addition in high-latitude ecosystems, and identified absent or poorly parameterized mechanisms in CLM4.5. While the two model versions predicted similar soil carbon stock trajectories following both warming and nitrogen addition, other predicted variables (e.g., belowgroundmore » respiration) differed from observations in both magnitude and direction, indicating that CLM4.5 has inadequate underlying mechanisms for representing high-latitude ecosystems. On the basis of observational synthesis, we attribute the model–observation differences to missing representations of microbial dynamics, aboveground and belowground coupling, and nutrient cycling, and we use the observational meta-analysis to discuss potential approaches to improving the current models. However, we also urge caution concerning the selection of data sets and experiments for meta-analysis. For example, the concentrations of nitrogen applied in the synthesized field experiments (average = 72 kg ha -1 yr -1) are many times higher than projected soil nitrogen concentrations (from nitrogen deposition and release during mineralization), which precludes a rigorous evaluation of the model responses to likely nitrogen perturbations. Overall, we demonstrate that elucidating ecological mechanisms via meta-analysis can identify deficiencies in ecosystem models and empirical experiments.« less

Basic Lessons in *ORA and Automap 2009

DTIC Science & Technology

2009-06-01

screen capture showing the visualization of the agent x event graph from the Stargate Summit Meta-Network. The visualization displays the connections...for the Stargate dataset. 25.2 lessons - 201-207 A step by step run through of creating the Meta-Network from working with Excel, exporting data to...For the purpose of creating the Stargate MetaNetwork the two-episode story arc (Summit / Last Stand) was choosen as the basis for all the nodes

Humor styles and personality: A meta-analysis of the relation between humor styles and the Big Five personality traits.

PubMed

Mendiburo-Seguel, Andrés; Páez, Darío; Martínez-Sánchez, Francisco

2015-06-01

This research summarizes the knowledge generated in social psychology and positive psychology about the relationship between humor styles, personality and wellbeing. Specifically, a meta-analysis was performed with the results of 15 studies on humor styles measured by the Humor Styles Questionnaire (Martin, Puhlik-Doris, Larsen, Gray & Weir, 2003) in correlation with the personality traits measured by the Big Five Personality model (measured with different scales). Following the steps presented by Rosenthal (1991) for meta-analysis in the case of correlational research, we calculated the total mean r as an indicator of effect size. Results show that affiliative humor has a strong and homogeneous relation to neuroticism and extraversion. The homogeneity and heterogeneity found between variables and possible explanations are discussed in the conclusion. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Applying Meta-Analysis to Structural Equation Modeling

ERIC Educational Resources Information Center

Hedges, Larry V.

2016-01-01

Structural equation models play an important role in the social sciences. Consequently, there is an increasing use of meta-analytic methods to combine evidence from studies that estimate the parameters of structural equation models. Two approaches are used to combine evidence from structural equation models: A direct approach that combines…

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study

PubMed Central

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-01-01

Background: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. Methods: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. Results: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917–0.942), 0.918 (0.905–0.930), 0.914 (0.886–0.936) and 0.875 (0.853–0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90–96%, specificity 74–79% and diagnostic odds ratio (DOR) 32.8–50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6–75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. Conclusions: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference. PMID:24937676

MPA Portable: A Stand-Alone Software Package for Analyzing Metaproteome Samples on the Go.

PubMed

Muth, Thilo; Kohrs, Fabian; Heyer, Robert; Benndorf, Dirk; Rapp, Erdmann; Reichl, Udo; Martens, Lennart; Renard, Bernhard Y

2018-01-02

Metaproteomics, the mass spectrometry-based analysis of proteins from multispecies samples faces severe challenges concerning data analysis and results interpretation. To overcome these shortcomings, we here introduce the MetaProteomeAnalyzer (MPA) Portable software. In contrast to the original server-based MPA application, this newly developed tool no longer requires computational expertise for installation and is now independent of any relational database system. In addition, MPA Portable now supports state-of-the-art database search engines and a convenient command line interface for high-performance data processing tasks. While search engine results can easily be combined to increase the protein identification yield, an additional two-step workflow is implemented to provide sufficient analysis resolution for further postprocessing steps, such as protein grouping as well as taxonomic and functional annotation. Our new application has been developed with a focus on intuitive usability, adherence to data standards, and adaptation to Web-based workflow platforms. The open source software package can be found at https://github.com/compomics/meta-proteome-analyzer .

Node-Splitting Generalized Linear Mixed Models for Evaluation of Inconsistency in Network Meta-Analysis.

PubMed

Yu-Kang, Tu

2016-12-01

Network meta-analysis for multiple treatment comparisons has been a major development in evidence synthesis methodology. The validity of a network meta-analysis, however, can be threatened by inconsistency in evidence within the network. One particular issue of inconsistency is how to directly evaluate the inconsistency between direct and indirect evidence with regard to the effects difference between two treatments. A Bayesian node-splitting model was first proposed and a similar frequentist side-splitting model has been put forward recently. Yet, assigning the inconsistency parameter to one or the other of the two treatments or splitting the parameter symmetrically between the two treatments can yield different results when multi-arm trials are involved in the evaluation. We aimed to show that a side-splitting model can be viewed as a special case of design-by-treatment interaction model, and different parameterizations correspond to different design-by-treatment interactions. We demonstrated how to evaluate the side-splitting model using the arm-based generalized linear mixed model, and an example data set was used to compare results from the arm-based models with those from the contrast-based models. The three parameterizations of side-splitting make slightly different assumptions: the symmetrical method assumes that both treatments in a treatment contrast contribute to inconsistency between direct and indirect evidence, whereas the other two parameterizations assume that only one of the two treatments contributes to this inconsistency. With this understanding in mind, meta-analysts can then make a choice about how to implement the side-splitting method for their analysis. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Predictive distributions were developed for the extent of heterogeneity in meta-analyses of continuous outcome data.

PubMed

Rhodes, Kirsty M; Turner, Rebecca M; Higgins, Julian P T

2015-01-01

Estimation of between-study heterogeneity is problematic in small meta-analyses. Bayesian meta-analysis is beneficial because it allows incorporation of external evidence on heterogeneity. To facilitate this, we provide empirical evidence on the likely heterogeneity between studies in meta-analyses relating to specific research settings. Our analyses included 6,492 continuous-outcome meta-analyses within the Cochrane Database of Systematic Reviews. We investigated the influence of meta-analysis settings on heterogeneity by modeling study data from all meta-analyses on the standardized mean difference scale. Meta-analysis setting was described according to outcome type, intervention comparison type, and medical area. Predictive distributions for between-study variance expected in future meta-analyses were obtained, which can be used directly as informative priors. Among outcome types, heterogeneity was found to be lowest in meta-analyses of obstetric outcomes. Among intervention comparison types, heterogeneity was lowest in meta-analyses comparing two pharmacologic interventions. Predictive distributions are reported for different settings. In two example meta-analyses, incorporating external evidence led to a more precise heterogeneity estimate. Heterogeneity was influenced by meta-analysis characteristics. Informative priors for between-study variance were derived for each specific setting. Our analyses thus assist the incorporation of realistic prior information into meta-analyses including few studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Meta-analysis inside and outside particle physics: two traditions that should converge?

PubMed

Baker, Rose D; Jackson, Dan

2013-06-01

The use of meta-analysis in medicine and epidemiology really took off in the 1970s. However, in high-energy physics, the Particle Data Group has been carrying out meta-analyses of measurements of particle masses and other properties since 1957. Curiously, there has been virtually no interaction between those working inside and outside particle physics. In this paper, we use statistical models to study two major differences in practice. The first is the usefulness of systematic errors, which physicists are now beginning to quote in addition to statistical errors. The second is whether it is better to treat heterogeneity by scaling up errors as do the Particle Data Group or by adding a random effect as does the rest of the community. Besides fitting models, we derive and use an exact test of the error-scaling hypothesis. We also discuss the other methodological differences between the two streams of meta-analysis. Our conclusion is that systematic errors are not currently very useful and that the conventional random effects model, as routinely used in meta-analysis, has a useful role to play in particle physics. The moral we draw for statisticians is that we should be more willing to explore 'grassroots' areas of statistical application, so that good statistical practice can flow both from and back to the statistical mainstream. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Accounting for heterogeneity in meta-analysis using a multiplicative model-an empirical study.

PubMed

Mawdsley, David; Higgins, Julian P T; Sutton, Alex J; Abrams, Keith R

2017-03-01

In meta-analysis, the random-effects model is often used to account for heterogeneity. The model assumes that heterogeneity has an additive effect on the variance of effect sizes. An alternative model, which assumes multiplicative heterogeneity, has been little used in the medical statistics community, but is widely used by particle physicists. In this paper, we compare the two models using a random sample of 448 meta-analyses drawn from the Cochrane Database of Systematic Reviews. In general, differences in goodness of fit are modest. The multiplicative model tends to give results that are closer to the null, with a narrower confidence interval. Both approaches make different assumptions about the outcome of the meta-analysis. In our opinion, the selection of the more appropriate model will often be guided by whether the multiplicative model's assumption of a single effect size is plausible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Primer on Systematic Reviews and Meta-Analyses.

PubMed

Nguyen, Nghia H; Singh, Siddharth

2018-05-01

With the rapid growth of biomedical literature, there is increasing need to make meaningful inferences from a comprehensive and complex body of evidence. Systematic reviews with or without meta-analyses offer an objective and summative approach to synthesize knowledge and critically appraise evidence to inform clinical practice. Systematic reviews also help identify key knowledge gaps for future investigation. In this review, the authors provide a step-by-step approach to conducting a systematic review. These include: (1) formulating a focused and clinically-relevant question; (2) designing a detailed review protocol with explicit inclusion and exclusion criteria; (3) performing a systematic literature search of multiple databases and unpublished data, in consultation with a medical librarian, to identify relevant studies; (4) meticulous data abstraction by at least two sets of investigators independently; (5) assessing risk of bias in individual studies; (6) quantitative synthesis with meta-analysis; and (7) critically and transparently ascertaining quality of evidence. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Multistep estimators of the between-study variance: The relationship with the Paule-Mandel estimator.

PubMed

van Aert, Robbie C M; Jackson, Dan

2018-04-26

A wide variety of estimators of the between-study variance are available in random-effects meta-analysis. Many, but not all, of these estimators are based on the method of moments. The DerSimonian-Laird estimator is widely used in applications, but the Paule-Mandel estimator is an alternative that is now recommended. Recently, DerSimonian and Kacker have developed two-step moment-based estimators of the between-study variance. We extend these two-step estimators so that multiple (more than two) steps are used. We establish the surprising result that the multistep estimator tends towards the Paule-Mandel estimator as the number of steps becomes large. Hence, the iterative scheme underlying our new multistep estimator provides a hitherto unknown relationship between two-step estimators and Paule-Mandel estimator. Our analysis suggests that two-step estimators are not necessarily distinct estimators in their own right; instead, they are quantities that are closely related to the usual iterative scheme that is used to calculate the Paule-Mandel estimate. The relationship that we establish between the multistep and Paule-Mandel estimator is another justification for the use of the latter estimator. Two-step and multistep estimators are perhaps best conceptualized as approximate Paule-Mandel estimators. © 2018 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

[Comparison of simple pooling and bivariate model used in meta-analyses of diagnostic test accuracy published in Chinese journals].

PubMed

Huang, Yuan-sheng; Yang, Zhi-rong; Zhan, Si-yan

2015-06-18

To investigate the use of simple pooling and bivariate model in meta-analyses of diagnostic test accuracy (DTA) published in Chinese journals (January to November, 2014), compare the differences of results from these two models, and explore the impact of between-study variability of sensitivity and specificity on the differences. DTA meta-analyses were searched through Chinese Biomedical Literature Database (January to November, 2014). Details in models and data for fourfold table were extracted. Descriptive analysis was conducted to investigate the prevalence of the use of simple pooling method and bivariate model in the included literature. Data were re-analyzed with the two models respectively. Differences in the results were examined by Wilcoxon signed rank test. How the results differences were affected by between-study variability of sensitivity and specificity, expressed by I2, was explored. The 55 systematic reviews, containing 58 DTA meta-analyses, were included and 25 DTA meta-analyses were eligible for re-analysis. Simple pooling was used in 50 (90.9%) systematic reviews and bivariate model in 1 (1.8%). The remaining 4 (7.3%) articles used other models pooling sensitivity and specificity or pooled neither of them. Of the reviews simply pooling sensitivity and specificity, 41(82.0%) were at the risk of wrongly using Meta-disc software. The differences in medians of sensitivity and specificity between two models were both 0.011 (P<0.001, P=0.031 respectively). Greater differences could be found as I2 of sensitivity or specificity became larger, especially when I2>75%. Most DTA meta-analyses published in Chinese journals(January to November, 2014) combine the sensitivity and specificity by simple pooling. Meta-disc software can pool the sensitivity and specificity only through fixed-effect model, but a high proportion of authors think it can implement random-effect model. Simple pooling tends to underestimate the results compared with bivariate model. The greater the between-study variance is, the more likely the simple pooling has larger deviation. It is necessary to increase the knowledge level of statistical methods and software for meta-analyses of DTA data.

Is There a Magnet School Effect? Using Meta-Analysis to Explore Variation in Magnet School Success. CRESST Report 843

ERIC Educational Resources Information Center

Wang, Jia; Schweig, Jonathan D.; Herman, Joan L.

2014-01-01

Magnet schools are one of the largest sectors of choice schools in the United States. In this study, we explored whether there is heterogeneity in magnet school effects on student achievement by examining the effectiveness of 24 recently funded magnet schools in 5 school districts across 4 states. We used a two-step analysis: First, separate…

Meta-analysis of high-latitude nitrogen-addition and warming studies imply ecological mechanisms overlooked by land models

NASA Astrophysics Data System (ADS)

Bouskill, N. J.; Riley, W. J.; Tang, J.

2014-08-01

Accurate representation of ecosystem processes in land models is crucial for reducing predictive uncertainty in energy and greenhouse gas feedbacks with the atmosphere. Here we describe an observational and modeling meta-analysis approach to benchmark land models, and apply the method to the land model CLM4.5 with two versions of belowground biogeochemistry. We focused our analysis on the above and belowground high-latitude ecosystem responses to warming and nitrogen addition, and identified mechanisms absent, or poorly parameterized in CLM4.5. While the two model versions predicted similar trajectories for soil carbon stocks following both types of perturbation, other variables (e.g., belowground respiration) differed from the observations in both magnitude and direction, indicating the underlying mechanisms are inadequate for representing high-latitude ecosystems. The observational synthesis attribute these differences to missing representations of microbial dynamics, characterization of above and belowground functional processes, and nutrient competition. We use the observational meta-analyses to discuss potential approaches to improving the current models (e.g., the inclusion of dynamic vegetation or different microbial functional guilds), however, we also raise a cautionary note on the selection of data sets and experiments to be included in a meta-analysis. For example, the concentrations of nitrogen applied in the synthesized field experiments (average =72 kg ha-1 yr-1) are many times higher than projected soil nitrogen concentrations (from nitrogen deposition and release during mineralization), which preclude a rigorous evaluation of the model responses to nitrogen perturbation. Overall, we demonstrate here that elucidating ecological mechanisms via meta-analysis can identify deficiencies in both ecosystem models and empirical experiments.

Meta-analysis of high-latitude nitrogen-addition and warming studies imply ecological mechanisms overlooked by land models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bouskill, N. J.; Riley, W. J.; Tang, J.

2014-08-18

Accurate representation of ecosystem processes in land models is crucial for reducing predictive uncertainty in energy and greenhouse gas feedbacks with the atmosphere. Here we describe an observational and modeling meta-analysis approach to benchmark land models, and apply the method to the land model CLM4.5 with two versions of belowground biogeochemistry. We focused our analysis on the above and belowground high-latitude ecosystem responses to warming and nitrogen addition, and identified mechanisms absent, or poorly parameterized in CLM4.5. While the two model versions predicted similar trajectories for soil carbon stocks following both types of perturbation, other variables (e.g., belowground respiration) differedmore » from the observations in both magnitude and direction, indicating the underlying mechanisms are inadequate for representing high-latitude ecosystems. The observational synthesis attribute these differences to missing representations of microbial dynamics, characterization of above and belowground functional processes, and nutrient competition. We use the observational meta-analyses to discuss potential approaches to improving the current models (e.g., the inclusion of dynamic vegetation or different microbial functional guilds), however, we also raise a cautionary note on the selection of data sets and experiments to be included in a meta-analysis. For example, the concentrations of nitrogen applied in the synthesized field experiments (average =72 kg ha -1 yr -1) are many times higher than projected soil nitrogen concentrations (from nitrogen deposition and release during mineralization), which preclude a rigorous evaluation of the model responses to nitrogen perturbation. Overall, we demonstrate here that elucidating ecological mechanisms via meta-analysis can identify deficiencies in both ecosystem models and empirical experiments.« less

A refined method for multivariate meta-analysis and meta-regression.

PubMed

Jackson, Daniel; Riley, Richard D

2014-02-20

Making inferences about the average treatment effect using the random effects model for meta-analysis is problematic in the common situation where there is a small number of studies. This is because estimates of the between-study variance are not precise enough to accurately apply the conventional methods for testing and deriving a confidence interval for the average effect. We have found that a refined method for univariate meta-analysis, which applies a scaling factor to the estimated effects' standard error, provides more accurate inference. We explain how to extend this method to the multivariate scenario and show that our proposal for refined multivariate meta-analysis and meta-regression can provide more accurate inferences than the more conventional approach. We explain how our proposed approach can be implemented using standard output from multivariate meta-analysis software packages and apply our methodology to two real examples. Copyright © 2013 John Wiley & Sons, Ltd.

Indirect health costs in ulcerative colitis and Crohn's disease: a systematic review and meta-analysis.

PubMed

Kawalec, Paweł; Malinowski, Krzysztof Piotr

2015-04-01

The aim of this systematic review was to collect all current data on indirect costs related to inflammatory bowel disease as well as assessing homogeneity and comparability, and conducting a meta-analysis. Costs were collected using databases from Medline, Embase and Centre for Reviews and Dissemination databases, then average annual cost per patient was calculated and expressed in 2013-rate USD using the consumer price index and purchasing power parity (scenario 1) and then adjusted to specific gross domestic product (scenario 2) to make them comparable. The studies were then included in quantitative synthesis using the meta-analysis and bootstrap methods. This systematic review was carried out and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. From 18 publications, overall annual indirect costs per patient as a result of the quantitative synthesis among all studies eligible for meta-analysis ranged from US$2425.01-US$9622.15 depending on the scenario and model used for analysis. The cost of presenteeism was assessed in only two studies. Considering heterogeneity among all identified studies random-effect model presented the most accurate results of meta-analysis equal to US$7189.27 and US$9622.15 per patient per year for scenario 1 and scenario 2, respectively. This systematic review revealed the existence of a relatively small number of studies that reported on the great economic burden of the disease upon society. A great variety of methodologies and cost components resulted in a very large discrepancy in indirect costs and made meta-analysis difficult to perform, so two scenarios were considered and meta-analysis conducted in subgroups to make data more comparable.

Characterization of Folding Mechanisms of Trp-cage and WW-domain by Network Analysis of Simulations with a Hybrid-resolution Model

PubMed Central

Han, Wei; Schulten, Klaus

2013-01-01

In this study, we apply a hybrid-resolution model, namely PACE, to characterize the free energy surfaces (FESs) of trp-cage and a WW domain variant along with the respective folding mechanisms. Unbiased, independent simulations with PACE are found to achieve together multiple folding and unfolding events for both proteins, allowing us to perform network analysis of the FESs to identify folding pathways. PACE reproduces for both proteins expected complexity hidden in the folding FESs, in particular, meta-stable non-native intermediates. Pathway analysis shows that some of these intermediates are, actually, on-pathway folding intermediates and that intermediates kinetically closest to the native states can be either critical on-pathway or off-pathway intermediates, depending on the protein. Apart from general insights into folding, specific folding mechanisms of the proteins are resolved. We find that trp-cage folds via a dominant pathway in which hydrophobic collapse occurs before the N-terminal helix forms; full incorporation of Trp6 into the hydrophobic core takes place as the last step of folding, which, however, may not be the rate-limiting step. For the WW domain variant studied we observe two main folding pathways with opposite orders of formation of the two hairpins involved in the structure; for either pathway, formation of hairpin 1 is more likely to be the rate-limiting step. Altogether, our results suggest that PACE combined with network analysis is a computationally efficient and valuable tool for the study of protein folding. PMID:23915394

Integrating landscape system and meta-ecosystem frameworks to advance the understanding of ecosystem function in heterogeneous landscapes: An analysis on the carbon fluxes in the Northern Highlands Lake District (NHLD) of Wisconsin and Michigan.

PubMed

Yang, Haile; Chen, Jiakuan

2018-01-01

The successful integration of ecosystem ecology with landscape ecology would be conducive to understanding how landscapes function. There have been several attempts at this, with two main approaches: (1) an ecosystem-based approach, such as the meta-ecosystem framework and (2) a landscape-based approach, such as the landscape system framework. These two frameworks are currently disconnected. To integrate these two frameworks, we introduce a protocol, and then demonstrate application of the protocol using a case study. The protocol includes four steps: 1) delineating landscape systems; 2) classifying landscape systems; 3) adjusting landscape systems to meta-ecosystems and 4) integrating landscape system and meta-ecosystem frameworks through meta-ecosystems. The case study is the analyzing of the carbon fluxes in the Northern Highlands Lake District (NHLD) of Wisconsin and Michigan using this protocol. The application of this protocol revealed that one could follow this protocol to construct a meta-ecosystem and analyze it using the integrative framework of landscape system and meta-ecosystem frameworks. That is, one could (1) appropriately describe and analyze the spatial heterogeneity of the meta-ecosystem; (2) understand the emergent properties arising from spatial coupling of local ecosystems in the meta-ecosystem. In conclusion, this protocol is a useful approach for integrating the meta-ecosystem framework and the landscape system framework, which advances the describing and analyzing of the spatial heterogeneity and ecosystem function of interconnected ecosystems.

Integrating landscape system and meta-ecosystem frameworks to advance the understanding of ecosystem function in heterogeneous landscapes: An analysis on the carbon fluxes in the Northern Highlands Lake District (NHLD) of Wisconsin and Michigan

PubMed Central

Chen, Jiakuan

2018-01-01

The successful integration of ecosystem ecology with landscape ecology would be conducive to understanding how landscapes function. There have been several attempts at this, with two main approaches: (1) an ecosystem-based approach, such as the meta-ecosystem framework and (2) a landscape-based approach, such as the landscape system framework. These two frameworks are currently disconnected. To integrate these two frameworks, we introduce a protocol, and then demonstrate application of the protocol using a case study. The protocol includes four steps: 1) delineating landscape systems; 2) classifying landscape systems; 3) adjusting landscape systems to meta-ecosystems and 4) integrating landscape system and meta-ecosystem frameworks through meta-ecosystems. The case study is the analyzing of the carbon fluxes in the Northern Highlands Lake District (NHLD) of Wisconsin and Michigan using this protocol. The application of this protocol revealed that one could follow this protocol to construct a meta-ecosystem and analyze it using the integrative framework of landscape system and meta-ecosystem frameworks. That is, one could (1) appropriately describe and analyze the spatial heterogeneity of the meta-ecosystem; (2) understand the emergent properties arising from spatial coupling of local ecosystems in the meta-ecosystem. In conclusion, this protocol is a useful approach for integrating the meta-ecosystem framework and the landscape system framework, which advances the describing and analyzing of the spatial heterogeneity and ecosystem function of interconnected ecosystems. PMID:29415066

Meta-Analysis: An Approach to Interview Success.

ERIC Educational Resources Information Center

McCaslin, Mark; Carlson, Nancy M.

An initial research step, developing an effective interview strategy, presents unique challenges for novice and master research alike. To focus qualitative research in the human ecology of the study, the strategy presented in this paper used an initial interview protocol and preanalysis process, called meta-analysis, prior to developing the formal…

A Bayesian network meta-analysis for binary outcome: how to do it.

PubMed

Greco, Teresa; Landoni, Giovanni; Biondi-Zoccai, Giuseppe; D'Ascenzo, Fabrizio; Zangrillo, Alberto

2016-10-01

This study presents an overview of conceptual and practical issues of a network meta-analysis (NMA), particularly focusing on its application to randomised controlled trials with a binary outcome of interest. We start from general considerations on NMA to specifically appraise how to collect study data, structure the analytical network and specify the requirements for different models and parameter interpretations, with the ultimate goal of providing physicians and clinician-investigators a practical tool to understand pros and cons of NMA. Specifically, we outline the key steps, from the literature search to sensitivity analysis, necessary to perform a valid NMA of binomial data, exploiting Markov Chain Monte Carlo approaches. We also apply this analytical approach to a case study on the beneficial effects of volatile agents compared to total intravenous anaesthetics for surgery to further clarify the statistical details of the models, diagnostics and computations. Finally, datasets and models for the freeware WinBUGS package are presented for the anaesthetic agent example. © The Author(s) 2013.

Opium and bladder cancer: A systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer

PubMed Central

Afshari, Mahdi; Janbabaei, Ghasem; Bahrami, Mohammad Amin

2017-01-01

Objective The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis. Methods The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3. Results We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05–4.87) and 5.7 (1.9–16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6–7.7). Conclusion This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers. PMID:28586371

Statistical Analysis of Individual Participant Data Meta-Analyses: A Comparison of Methods and Recommendations for Practice

PubMed Central

Stewart, Gavin B.; Altman, Douglas G.; Askie, Lisa M.; Duley, Lelia; Simmonds, Mark C.; Stewart, Lesley A.

2012-01-01

Background Individual participant data (IPD) meta-analyses that obtain “raw” data from studies rather than summary data typically adopt a “two-stage” approach to analysis whereby IPD within trials generate summary measures, which are combined using standard meta-analytical methods. Recently, a range of “one-stage” approaches which combine all individual participant data in a single meta-analysis have been suggested as providing a more powerful and flexible approach. However, they are more complex to implement and require statistical support. This study uses a dataset to compare “two-stage” and “one-stage” models of varying complexity, to ascertain whether results obtained from the approaches differ in a clinically meaningful way. Methods and Findings We included data from 24 randomised controlled trials, evaluating antiplatelet agents, for the prevention of pre-eclampsia in pregnancy. We performed two-stage and one-stage IPD meta-analyses to estimate overall treatment effect and to explore potential treatment interactions whereby particular types of women and their babies might benefit differentially from receiving antiplatelets. Two-stage and one-stage approaches gave similar results, showing a benefit of using anti-platelets (Relative risk 0.90, 95% CI 0.84 to 0.97). Neither approach suggested that any particular type of women benefited more or less from antiplatelets. There were no material differences in results between different types of one-stage model. Conclusions For these data, two-stage and one-stage approaches to analysis produce similar results. Although one-stage models offer a flexible environment for exploring model structure and are useful where across study patterns relating to types of participant, intervention and outcome mask similar relationships within trials, the additional insights provided by their usage may not outweigh the costs of statistical support for routine application in syntheses of randomised controlled trials. Researchers considering undertaking an IPD meta-analysis should not necessarily be deterred by a perceived need for sophisticated statistical methods when combining information from large randomised trials. PMID:23056232

Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes--individual patient data (IPD) meta-analysis and health economic evaluation.

PubMed

Ruifrok, Anneloes E; Rogozinska, Ewelina; van Poppel, Mireille N M; Rayanagoudar, Girish; Kerry, Sally; de Groot, Christianne J M; Yeo, SeonAe; Molyneaux, Emma; McAuliffe, Fionnuala M; Poston, Lucilla; Roberts, Tracy; Riley, Richard D; Coomarasamy, Arri; Khan, Khalid; Mol, Ben Willem; Thangaratinam, Shakila

2014-11-04

Pregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women. Randomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research. PROSPERO 2013: CRD42013003804.

An overview of meta-analysis for clinicians.

PubMed

Lee, Young Ho

2018-03-01

The number of medical studies being published is increasing exponentially, and clinicians must routinely process large amounts of new information. Moreover, the results of individual studies are often insufficient to provide confident answers, as their results are not consistently reproducible. A meta-analysis is a statistical method for combining the results of different studies on the same topic and it may resolve conflicts among studies. Meta-analysis is being used increasingly and plays an important role in medical research. This review introduces the basic concepts, steps, advantages, and caveats of meta-analysis, to help clinicians understand it in clinical practice and research. A major advantage of a meta-analysis is that it produces a precise estimate of the effect size, with considerably increased statistical power, which is important when the power of the primary study is limited because of a small sample size. A meta-analysis may yield conclusive results when individual studies are inconclusive. Furthermore, meta-analyses investigate the source of variation and different effects among subgroups. In summary, a meta-analysis is an objective, quantitative method that provides less biased estimates on a specific topic. Understanding how to conduct a meta-analysis aids clinicians in the process of making clinical decisions.

Comparison of variance estimators for meta-analysis of instrumental variable estimates

PubMed Central

Schmidt, AF; Hingorani, AD; Jefferis, BJ; White, J; Groenwold, RHH; Dudbridge, F

2016-01-01

Abstract Background: Mendelian randomization studies perform instrumental variable (IV) analysis using genetic IVs. Results of individual Mendelian randomization studies can be pooled through meta-analysis. We explored how different variance estimators influence the meta-analysed IV estimate. Methods: Two versions of the delta method (IV before or after pooling), four bootstrap estimators, a jack-knife estimator and a heteroscedasticity-consistent (HC) variance estimator were compared using simulation. Two types of meta-analyses were compared, a two-stage meta-analysis pooling results, and a one-stage meta-analysis pooling datasets. Results: Using a two-stage meta-analysis, coverage of the point estimate using bootstrapped estimators deviated from nominal levels at weak instrument settings and/or outcome probabilities ≤ 0.10. The jack-knife estimator was the least biased resampling method, the HC estimator often failed at outcome probabilities ≤ 0.50 and overall the delta method estimators were the least biased. In the presence of between-study heterogeneity, the delta method before meta-analysis performed best. Using a one-stage meta-analysis all methods performed equally well and better than two-stage meta-analysis of greater or equal size. Conclusions: In the presence of between-study heterogeneity, two-stage meta-analyses should preferentially use the delta method before meta-analysis. Weak instrument bias can be reduced by performing a one-stage meta-analysis. PMID:27591262

A general framework for the use of logistic regression models in meta-analysis.

PubMed

Simmonds, Mark C; Higgins, Julian Pt

2016-12-01

Where individual participant data are available for every randomised trial in a meta-analysis of dichotomous event outcomes, "one-stage" random-effects logistic regression models have been proposed as a way to analyse these data. Such models can also be used even when individual participant data are not available and we have only summary contingency table data. One benefit of this one-stage regression model over conventional meta-analysis methods is that it maximises the correct binomial likelihood for the data and so does not require the common assumption that effect estimates are normally distributed. A second benefit of using this model is that it may be applied, with only minor modification, in a range of meta-analytic scenarios, including meta-regression, network meta-analyses and meta-analyses of diagnostic test accuracy. This single model can potentially replace the variety of often complex methods used in these areas. This paper considers, with a range of meta-analysis examples, how random-effects logistic regression models may be used in a number of different types of meta-analyses. This one-stage approach is compared with widely used meta-analysis methods including Bayesian network meta-analysis and the bivariate and hierarchical summary receiver operating characteristic (ROC) models for meta-analyses of diagnostic test accuracy. © The Author(s) 2014.

A refined method for multivariate meta-analysis and meta-regression

PubMed Central

Jackson, Daniel; Riley, Richard D

2014-01-01

Making inferences about the average treatment effect using the random effects model for meta-analysis is problematic in the common situation where there is a small number of studies. This is because estimates of the between-study variance are not precise enough to accurately apply the conventional methods for testing and deriving a confidence interval for the average effect. We have found that a refined method for univariate meta-analysis, which applies a scaling factor to the estimated effects’ standard error, provides more accurate inference. We explain how to extend this method to the multivariate scenario and show that our proposal for refined multivariate meta-analysis and meta-regression can provide more accurate inferences than the more conventional approach. We explain how our proposed approach can be implemented using standard output from multivariate meta-analysis software packages and apply our methodology to two real examples. © 2013 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:23996351

An investigation of the impact of using different methods for network meta-analysis: a protocol for an empirical evaluation.

PubMed

Karahalios, Amalia Emily; Salanti, Georgia; Turner, Simon L; Herbison, G Peter; White, Ian R; Veroniki, Areti Angeliki; Nikolakopoulou, Adriani; Mckenzie, Joanne E

2017-06-24

Network meta-analysis, a method to synthesise evidence from multiple treatments, has increased in popularity in the past decade. Two broad approaches are available to synthesise data across networks, namely, arm- and contrast-synthesis models, with a range of models that can be fitted within each. There has been recent debate about the validity of the arm-synthesis models, but to date, there has been limited empirical evaluation comparing results using the methods applied to a large number of networks. We aim to address this gap through the re-analysis of a large cohort of published networks of interventions using a range of network meta-analysis methods. We will include a subset of networks from a database of network meta-analyses of randomised trials that have been identified and curated from the published literature. The subset of networks will include those where the primary outcome is binary, the number of events and participants are reported for each direct comparison, and there is no evidence of inconsistency in the network. We will re-analyse the networks using three contrast-synthesis methods and two arm-synthesis methods. We will compare the estimated treatment effects, their standard errors, treatment hierarchy based on the surface under the cumulative ranking (SUCRA) curve, the SUCRA value, and the between-trial heterogeneity variance across the network meta-analysis methods. We will investigate whether differences in the results are affected by network characteristics and baseline risk. The results of this study will inform whether, in practice, the choice of network meta-analysis method matters, and if it does, in what situations differences in the results between methods might arise. The results from this research might also inform future simulation studies.

A qualitative meta-synthesis and theory of postpartum depression.

PubMed

Mollard, Elizabeth K

2014-09-01

To synthesize existing qualitative literature on the first-hand experiences of women suffering from postpartum depression (PPD), to uncover potential common themes, a meta-synthesis of 12 qualitative studies using Noblit and Hare's 7-phase model of meta-ethnography was used. Four themes were discovered: crushed maternal role expectation, going into hiding, loss of sense of self, intense feelings of vulnerability, plus practical life concerns. A preliminary theory of PPD as a 4-step process is proposed, based on the relationships between the themes in this meta-synthesis. This 4-step process is compared and contrasted with Cheryl Tatano Beck's 4-stage theory of PPD "Teetering on the Edge". This meta-synthesis and theory offers a significant contribution to the literature in helping identify PPD distinctly from depression outside of the postpartum period, and deserves further study.

How to Perform a Systematic Review and Meta-analysis of Diagnostic Imaging Studies.

PubMed

Cronin, Paul; Kelly, Aine Marie; Altaee, Duaa; Foerster, Bradley; Petrou, Myria; Dwamena, Ben A

2018-05-01

A systematic review is a comprehensive search, critical evaluation, and synthesis of all the relevant studies on a specific (clinical) topic that can be applied to the evaluation of diagnostic and screening imaging studies. It can be a qualitative or a quantitative (meta-analysis) review of available literature. A meta-analysis uses statistical methods to combine and summarize the results of several studies. In this review, a 12-step approach to performing a systematic review (and meta-analysis) is outlined under the four domains: (1) Problem Formulation and Data Acquisition, (2) Quality Appraisal of Eligible Studies, (3) Statistical Analysis of Quantitative Data, and (4) Clinical Interpretation of the Evidence. This review is specifically geared toward the performance of a systematic review and meta-analysis of diagnostic test accuracy (imaging) studies. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach

PubMed Central

Chen, Yong; Hong, Chuan; Ning, Yang; Su, Xiao

2018-01-01

When conducting a meta-analysis of studies with bivariate binary outcomes, challenges arise when the within-study correlation and between-study heterogeneity should be taken into account. In this paper, we propose a marginal beta-binomial model for the meta-analysis of studies with binary outcomes. This model is based on the composite likelihood approach, and has several attractive features compared to the existing models such as bivariate generalized linear mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al., 2012). The advantages of the proposed marginal model include modeling the probabilities in the original scale, not requiring any transformation of probabilities or any link function, having closed-form expression of likelihood function, and no constraints on the correlation parameter. More importantly, since the marginal beta-binomial model is only based on the marginal distributions, it does not suffer from potential misspecification of the joint distribution of bivariate study-specific probabilities. Such misspecification is difficult to detect and can lead to biased inference using currents methods. We compare the performance of the marginal beta-binomial model with the bivariate generalized linear mixed model and the Sarmanov beta-binomial model by simulation studies. Interestingly, the results show that the marginal beta-binomial model performs better than the Sarmanov beta-binomial model, whether or not the true model is Sarmanov beta-binomial, and the marginal beta-binomial model is more robust than the bivariate generalized linear mixed model under model misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta-analysis of case-control studies are conducted for illustration. PMID:26303591

Efficacy of preparation solutions and cleansing techniques on contamination of the skin in foot and ankle surgery: A systematic review and meta-analysis.

PubMed

Yammine, K; Harvey, A

2013-04-01

We report a systematic review and meta-analysis of published randomised and quasi-randomised trials evaluating the efficacy of pre-operative skin antisepsis and cleansing techniques in reducing foot and ankle skin flora. The post-preparation culture number (Post-PCN) was the primary outcome. The data were evaluated using a modified version of the Cochrane Collaboration’s tool. We identified eight trials (560 participants, 716 feet) that met the inclusion criteria. There was a significant difference in the proportions of Post-PCN between hallux nailfold (HNF) and toe web spaces (TWS) sites: 0.47 vs 0.22, respectively (95% confidence interval (CI) 0.182937 to 0.304097; p < 0.0001). Meta-analyses showed that alcoholic chlorhexidine had better efficacy than alcoholic povidone-iodine (PI) at HNF sites (risk difference 0.19 (95% CI 0.08 to 0.30); p = 0.0005); a two-step intervention using PI scrub and paint (S&P) followed by alcohol showed significantly better efficacy over PI (S&P) alone at TWS sites (risk difference 0.13 (95% CI 0.02 to 0.24); p = 0.0169); and a two-step intervention using chlorhexidine scrub followed by alcohol showed significantly better efficacy over PI (S&P) alone at the combined (HNF with TWS) sites (risk difference 0.27 (95% CI 0.13 to 0.40); p < 0.0001). No significant difference was found between cleansing techniques.

Self-help cognitive-behavioral therapy for insomnia: a meta-analysis of randomized controlled trials.

PubMed

Ho, Fiona Yan-Yee; Chung, Ka-Fai; Yeung, Wing-Fai; Ng, Tommy H; Kwan, Ka-Shing; Yung, Kam-Ping; Cheng, Sammy K

2015-02-01

Self-help cognitive-behavioral therapy (CBT) is an increasingly popular treatment option for insomnia. The objective of this meta-analysis was to compile an up-to-date evaluation on the efficacy, adherence, acceptability and dropout rate of self-help CBT for insomnia. We systematically searched six key electronic databases up until May 2013. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. Twenty randomized controlled trials were included; 10 of which were published after the last review up until January 2007. Meta-analysis of self-help CBT vs. waiting-list, routine care or no treatment was performed. Results showed that self-help CBT improved sleep, sleep-related cognitions and anxiety and depressive symptoms. Effect sizes for sleep-diary-derived sleep efficiency, sleep onset latency, and wake after sleep onset at immediate posttreatment were 0.80, 0.66, and 0.55, respectively. The average dropout rate of self-help CBT at immediate posttreatment was 14.5%, which was not significantly different from the 16.7% in therapist-administered CBT. Subgroup analyses supported the added benefit of telephone consultation. In conclusion, self-help CBT is efficacious and acceptable as an entry level of a stepped care model for insomnia. In places where face-to-face treatments are unavailable or too costly, self-help CBT can be considered as a compromise. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness of exercise programs to reduce falls in older people with dementia living in the community: a systematic review and meta-analysis

PubMed Central

Burton, Elissa; Cavalheri, Vinicius; Adams, Richard; Oakley Browne, Colleen; Bovery-Spencer, Petra; Fenton, Audra M; Campbell, Bruce W; Hill, Keith D

2015-01-01

Objective The objective of this systematic review and meta-analysis is to evaluate the effectiveness of exercise programs to reduce falls in older people with dementia who are living in the community. Method Peer-reviewed articles (randomized controlled trials [RCTs] and quasi-experimental trials) published in English between January 2000 and February 2014, retrieved from six electronic databases – Medline (ProQuest), CINAHL, PubMed, PsycInfo, EMBASE and Scopus – according to predefined inclusion criteria were included. Where possible, results were pooled and meta-analysis was conducted. Results Four articles (three RCT and one single-group pre- and post-test pilot study) were included. The study quality of the three RCTs was high; however, measurement outcomes, interventions, and follow-up time periods differed across studies. On completion of the intervention period, the mean number of falls was lower in the exercise group compared to the control group (mean difference [MD] [95% confidence interval {CI}] =−1.06 [−1.67 to −0.46] falls). Importantly, the exercise intervention reduced the risk of being a faller by 32% (risk ratio [95% CI] =0.68 [0.55–0.85]). Only two other outcomes were reported in two or more of the studies (step test and physiological profile assessment). No between-group differences were observed in the results of the step test (number of steps) (MD [95% CI] =0.51 [−1.77 to 2.78]) or the physiological profile assessment (MD [95% CI] =−0.10 [−0.62 to 0.42]). Conclusion Findings from this review suggest that an exercise program may potentially assist in preventing falls of older people with dementia living in the community. However, further research is needed with studies using larger sample sizes, standardized measurement outcomes, and longer follow-up periods, to inform evidence-based recommendations. PMID:25709416

An analysis of iterated local search for job-shop scheduling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitley, L. Darrell; Howe, Adele E.; Watson, Jean-Paul

2003-08-01

Iterated local search, or ILS, is among the most straightforward meta-heuristics for local search. ILS employs both small-step and large-step move operators. Search proceeds via iterative modifications to a single solution, in distinct alternating phases. In the first phase, local neighborhood search (typically greedy descent) is used in conjunction with the small-step operator to transform solutions into local optima. In the second phase, the large-step operator is applied to generate perturbations to the local optima obtained in the first phase. Ideally, when local neighborhood search is applied to the resulting solution, search will terminate at a different local optimum, i.e.,more » the large-step perturbations should be sufficiently large to enable escape from the attractor basins of local optima. ILS has proven capable of delivering excellent performance on numerous N P-Hard optimization problems. [LMS03]. However, despite its implicity, very little is known about why ILS can be so effective, and under what conditions. The goal of this paper is to advance the state-of-the-art in the analysis of meta-heuristics, by providing answers to this research question. They focus on characterizing both the relationship between the structure of the underlying search space and ILS performance, and the dynamic behavior of ILS. The analysis proceeds in the context of the job-shop scheduling problem (JSP) [Tai94]. They begin by demonstrating that the attractor basins of local optima in the JSP are surprisingly weak, and can be escaped with high probaiblity by accepting a short random sequence of less-fit neighbors. this result is used to develop a new ILS algorithms for the JSP, I-JAR, whose performance is competitive with tabu search on difficult benchmark instances. They conclude by developing a very accurate behavioral model of I-JAR, which yields significant insights into the dynamics of search. The analysis is based on a set of 100 random 10 x 10 problem instances, in addition to some widely used benchmark instances. Both I-JAR and the tabu search algorithm they consider are based on the N1 move operator introduced by van Laarhoven et al. [vLAL92]. The N1 operator induces a connected search space, such that it is always possible to move from an arbitrary solution to an optimal solution; this property is integral to the development of a behavioral model of I-JAR. However, much of the analysis generalizes to other move operators, including that of Nowicki and Smutnick [NS96]. Finally the models are based on the distance between two solutions, which they take as the well-known disjunctive graph distance [MBK99].« less

Meta-analysis of quantitative pleiotropic traits for next-generation sequencing with multivariate functional linear models

PubMed Central

Chiu, Chi-yang; Jung, Jeesun; Chen, Wei; Weeks, Daniel E; Ren, Haobo; Boehnke, Michael; Amos, Christopher I; Liu, Aiyi; Mills, James L; Ting Lee, Mei-ling; Xiong, Momiao; Fan, Ruzong

2017-01-01

To analyze next-generation sequencing data, multivariate functional linear models are developed for a meta-analysis of multiple studies to connect genetic variant data to multiple quantitative traits adjusting for covariates. The goal is to take the advantage of both meta-analysis and pleiotropic analysis in order to improve power and to carry out a unified association analysis of multiple studies and multiple traits of complex disorders. Three types of approximate F -distributions based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants. Simulation analysis is performed to evaluate false-positive rates and power of the proposed tests. The proposed methods are applied to analyze lipid traits in eight European cohorts. It is shown that it is more advantageous to perform multivariate analysis than univariate analysis in general, and it is more advantageous to perform meta-analysis of multiple studies instead of analyzing the individual studies separately. The proposed models require individual observations. The value of the current paper can be seen at least for two reasons: (a) the proposed methods can be applied to studies that have individual genotype data; (b) the proposed methods can be used as a criterion for future work that uses summary statistics to build test statistics to meta-analyze the data. PMID:28000696

Meta-analysis of quantitative pleiotropic traits for next-generation sequencing with multivariate functional linear models.

PubMed

Chiu, Chi-Yang; Jung, Jeesun; Chen, Wei; Weeks, Daniel E; Ren, Haobo; Boehnke, Michael; Amos, Christopher I; Liu, Aiyi; Mills, James L; Ting Lee, Mei-Ling; Xiong, Momiao; Fan, Ruzong

2017-02-01

To analyze next-generation sequencing data, multivariate functional linear models are developed for a meta-analysis of multiple studies to connect genetic variant data to multiple quantitative traits adjusting for covariates. The goal is to take the advantage of both meta-analysis and pleiotropic analysis in order to improve power and to carry out a unified association analysis of multiple studies and multiple traits of complex disorders. Three types of approximate F -distributions based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants. Simulation analysis is performed to evaluate false-positive rates and power of the proposed tests. The proposed methods are applied to analyze lipid traits in eight European cohorts. It is shown that it is more advantageous to perform multivariate analysis than univariate analysis in general, and it is more advantageous to perform meta-analysis of multiple studies instead of analyzing the individual studies separately. The proposed models require individual observations. The value of the current paper can be seen at least for two reasons: (a) the proposed methods can be applied to studies that have individual genotype data; (b) the proposed methods can be used as a criterion for future work that uses summary statistics to build test statistics to meta-analyze the data.

Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis.

PubMed

Horvath, Karl; Koch, Klaus; Jeitler, Klaus; Matyas, Eva; Bender, Ralf; Bastian, Hilda; Lange, Stefan; Siebenhofer, Andrea

2010-04-01

To summarise the benefits and harms of treatments for women with gestational diabetes mellitus. Systematic review and meta-analysis of randomised controlled trials. Embase, Medline, AMED, BIOSIS, CCMed, CDMS, CDSR, CENTRAL, CINAHL, DARE, HTA, NHS EED, Heclinet, SciSearch, several publishers' databases, and reference lists of relevant secondary literature up to October 2009. Review methods Included studies were randomised controlled trials of specific treatment for gestational diabetes compared with usual care or "intensified" compared with "less intensified" specific treatment. Five randomised controlled trials matched the inclusion criteria for specific versus usual treatment. All studies used a two step approach with a 50 g glucose challenge test or screening for risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Meta-analyses did not show significant differences for most single end points judged to be of direct clinical importance. In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common (odds ratio 0.40, 95% confidence interval 0.21 to 0.75), and one randomised controlled trial reported a significant reduction of pre-eclampsia (2.5 v 5.5%, P=0.02). For the surrogate end point of large for gestational age infants, the odds ratio was 0.48 (0.38 to 0.62). In the 13 randomised controlled trials of different intensities of specific treatments, meta-analysis showed a significant reduction of shoulder dystocia in women with more intensive treatment (0.31, 0.14 to 0.70). Treatment for gestational diabetes, consisting of treatment to lower blood glucose concentration alone or with special obstetric care, seems to lower the risk for some perinatal complications. Decisions regarding treatment should take into account that the evidence of benefit is derived from trials for which women were selected with a two step strategy (glucose challenge test/screening for risk factors and oral glucose tolerance test).

Different patterns and development characteristics of processing written logographic characters and alphabetic words: an ALE meta-analysis.

PubMed

Zhu, Linlin; Nie, Yaoxin; Chang, Chunqi; Gao, Jia-Hong; Niu, Zhendong

2014-06-01

The neural systems for phonological processing of written language have been well identified now, while models based on these neural systems are different for different language systems or age groups. Although each of such models is mostly concordant across different experiments, the results are sensitive to the experiment design and intersubject variability. Activation likelihood estimation (ALE) meta-analysis can quantitatively synthesize the data from multiple studies and minimize the interstudy or intersubject differences. In this study, we performed two ALE meta-analysis experiments: one was to examine the neural activation patterns of the phonological processing of two different types of written languages and the other was to examine the development characteristics of such neural activation patterns based on both alphabetic language and logographic language data. The results of our first meta-analysis experiment were consistent with the meta-analysis which was based on the studies published before 2005. And there were new findings in our second meta-analysis experiment, where both adults and children groups showed great activation in the left frontal lobe, the left superior/middle temporal gyrus, and the bilateral middle/superior occipital gyrus. However, the activation of the left middle/inferior frontal gyrus was found increase with the development, and the activation was found decrease in the following areas: the right claustrum and inferior frontal gyrus, the left inferior/medial frontal gyrus, the left middle/superior temporal gyrus, the right cerebellum, and the bilateral fusiform gyrus. It seems that adults involve more phonological areas, whereas children involve more orthographic areas and semantic areas. Copyright © 2013 Wiley Periodicals, Inc.

A random effects meta-analysis model with Box-Cox transformation.

PubMed

Yamaguchi, Yusuke; Maruo, Kazushi; Partlett, Christopher; Riley, Richard D

2017-07-19

In a random effects meta-analysis model, true treatment effects for each study are routinely assumed to follow a normal distribution. However, normality is a restrictive assumption and the misspecification of the random effects distribution may result in a misleading estimate of overall mean for the treatment effect, an inappropriate quantification of heterogeneity across studies and a wrongly symmetric prediction interval. We focus on problems caused by an inappropriate normality assumption of the random effects distribution, and propose a novel random effects meta-analysis model where a Box-Cox transformation is applied to the observed treatment effect estimates. The proposed model aims to normalise an overall distribution of observed treatment effect estimates, which is sum of the within-study sampling distributions and the random effects distribution. When sampling distributions are approximately normal, non-normality in the overall distribution will be mainly due to the random effects distribution, especially when the between-study variation is large relative to the within-study variation. The Box-Cox transformation addresses this flexibly according to the observed departure from normality. We use a Bayesian approach for estimating parameters in the proposed model, and suggest summarising the meta-analysis results by an overall median, an interquartile range and a prediction interval. The model can be applied for any kind of variables once the treatment effect estimate is defined from the variable. A simulation study suggested that when the overall distribution of treatment effect estimates are skewed, the overall mean and conventional I 2 from the normal random effects model could be inappropriate summaries, and the proposed model helped reduce this issue. We illustrated the proposed model using two examples, which revealed some important differences on summary results, heterogeneity measures and prediction intervals from the normal random effects model. The random effects meta-analysis with the Box-Cox transformation may be an important tool for examining robustness of traditional meta-analysis results against skewness on the observed treatment effect estimates. Further critical evaluation of the method is needed.

Robust variance estimation with dependent effect sizes: practical considerations including a software tutorial in Stata and spss.

PubMed

Tanner-Smith, Emily E; Tipton, Elizabeth

2014-03-01

Methodologists have recently proposed robust variance estimation as one way to handle dependent effect sizes in meta-analysis. Software macros for robust variance estimation in meta-analysis are currently available for Stata (StataCorp LP, College Station, TX, USA) and spss (IBM, Armonk, NY, USA), yet there is little guidance for authors regarding the practical application and implementation of those macros. This paper provides a brief tutorial on the implementation of the Stata and spss macros and discusses practical issues meta-analysts should consider when estimating meta-regression models with robust variance estimates. Two example databases are used in the tutorial to illustrate the use of meta-analysis with robust variance estimates. Copyright © 2013 John Wiley & Sons, Ltd.

The influence of a consumer-wearable activity tracker on sedentary time and prolonged sedentary bouts: secondary analysis of a randomized controlled trial.

PubMed

Sloan, Robert A; Kim, Youngdeok; Sahasranaman, Aarti; Müller-Riemenschneider, Falk; Biddle, Stuart J H; Finkelstein, Eric A

2018-03-22

A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activity tracker to reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month randomized control trial where 800 employees from 13 organizations were assigned to control, activity tracker, or one of two activity tracker plus incentive groups designed to increase step count. The primary outcome was accelerometer measured moderate-to-vigorous physical activity. We conducted a secondary analysis on accelerometer measured daily ST and PSB bouts. A general linear mixed model was used to examine changes in ST and prolonged sedentary bouts, followed by between-group pairwise comparisons. Regression analyses were conducted to examine the association of changes in step counts with ST and PSB. The changes in ST and PSB were not statistically significant and not different between the groups (P < 0.05). Increases in step counts were concomitantly associated with decreases in ST and PSB, regardless of intervention (P < 0.05). Caution should be taken when considering consumer-wearable activity trackers as a means to reduce sedentary behavior. Trial registration NCT01855776 Registered: August 8, 2012.

A regulation probability model-based meta-analysis of multiple transcriptomics data sets for cancer biomarker identification.

PubMed

Xie, Xin-Ping; Xie, Yu-Feng; Wang, Hong-Qiang

2017-08-23

Large-scale accumulation of omics data poses a pressing challenge of integrative analysis of multiple data sets in bioinformatics. An open question of such integrative analysis is how to pinpoint consistent but subtle gene activity patterns across studies. Study heterogeneity needs to be addressed carefully for this goal. This paper proposes a regulation probability model-based meta-analysis, jGRP, for identifying differentially expressed genes (DEGs). The method integrates multiple transcriptomics data sets in a gene regulatory space instead of in a gene expression space, which makes it easy to capture and manage data heterogeneity across studies from different laboratories or platforms. Specifically, we transform gene expression profiles into a united gene regulation profile across studies by mathematically defining two gene regulation events between two conditions and estimating their occurring probabilities in a sample. Finally, a novel differential expression statistic is established based on the gene regulation profiles, realizing accurate and flexible identification of DEGs in gene regulation space. We evaluated the proposed method on simulation data and real-world cancer datasets and showed the effectiveness and efficiency of jGRP in identifying DEGs identification in the context of meta-analysis. Data heterogeneity largely influences the performance of meta-analysis of DEGs identification. Existing different meta-analysis methods were revealed to exhibit very different degrees of sensitivity to study heterogeneity. The proposed method, jGRP, can be a standalone tool due to its united framework and controllable way to deal with study heterogeneity.

Statistical strategies for averaging EC50 from multiple dose-response experiments.

PubMed

Jiang, Xiaoqi; Kopp-Schneider, Annette

2015-11-01

In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

Angry Birds, Angry Children, and Angry Meta-Analysts: A Reanalysis.

PubMed

Furuya-Kanamori, Luis; Doi, Suhail A R

2016-05-01

Ferguson's (2015a) meta-analysis assessed a very important and controversial topic about children's mental health and video games. In response to the concerns raised by researchers about the appropriateness of the meta-analytical methods used by Ferguson; we decided to reanalyze the data and discuss two major misconceptions about meta-analysis. We argue that partial correlations can (and should) be meta-analyzed instead of zero-order bivariate correlations if the predictors included in the partial correlation represent a similar construct. We also discuss the fallacy by which the conventional meta-analytical model assumes that the studies' effect sizes came into being according to the same random effect construct used by the analysis. Our replication results using partial correlations, standardized (valid and reliable) outcomes, and an improved meta-analytical model (that does not assume a random effect is the mechanism of data generation) confirmed the main results of Ferguson's meta-analysis. There was a significant yet very small effect on aggressive behavior of exposure to both general, rp = 0.062, 95% CI [0.012, 0.112], and violent, rp = 0.055, 95% CI [0.019, 0.091], video games. A very small effect was seen on reduced prosocial behavior, but this was only in the general video game exposure category, rp = 0.072, 95% CI [0.045, 0.100]. © The Author(s) 2016.

Measuring the statistical validity of summary meta-analysis and meta-regression results for use in clinical practice.

PubMed

Willis, Brian H; Riley, Richard D

2017-09-20

An important question for clinicians appraising a meta-analysis is: are the findings likely to be valid in their own practice-does the reported effect accurately represent the effect that would occur in their own clinical population? To this end we advance the concept of statistical validity-where the parameter being estimated equals the corresponding parameter for a new independent study. Using a simple ('leave-one-out') cross-validation technique, we demonstrate how we may test meta-analysis estimates for statistical validity using a new validation statistic, Vn, and derive its distribution. We compare this with the usual approach of investigating heterogeneity in meta-analyses and demonstrate the link between statistical validity and homogeneity. Using a simulation study, the properties of Vn and the Q statistic are compared for univariate random effects meta-analysis and a tailored meta-regression model, where information from the setting (included as model covariates) is used to calibrate the summary estimate to the setting of application. Their properties are found to be similar when there are 50 studies or more, but for fewer studies Vn has greater power but a higher type 1 error rate than Q. The power and type 1 error rate of Vn are also shown to depend on the within-study variance, between-study variance, study sample size, and the number of studies in the meta-analysis. Finally, we apply Vn to two published meta-analyses and conclude that it usefully augments standard methods when deciding upon the likely validity of summary meta-analysis estimates in clinical practice. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach.

PubMed

Chen, Yong; Hong, Chuan; Ning, Yang; Su, Xiao

2016-01-15

When conducting a meta-analysis of studies with bivariate binary outcomes, challenges arise when the within-study correlation and between-study heterogeneity should be taken into account. In this paper, we propose a marginal beta-binomial model for the meta-analysis of studies with binary outcomes. This model is based on the composite likelihood approach and has several attractive features compared with the existing models such as bivariate generalized linear mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al., 2012). The advantages of the proposed marginal model include modeling the probabilities in the original scale, not requiring any transformation of probabilities or any link function, having closed-form expression of likelihood function, and no constraints on the correlation parameter. More importantly, because the marginal beta-binomial model is only based on the marginal distributions, it does not suffer from potential misspecification of the joint distribution of bivariate study-specific probabilities. Such misspecification is difficult to detect and can lead to biased inference using currents methods. We compare the performance of the marginal beta-binomial model with the bivariate generalized linear mixed model and the Sarmanov beta-binomial model by simulation studies. Interestingly, the results show that the marginal beta-binomial model performs better than the Sarmanov beta-binomial model, whether or not the true model is Sarmanov beta-binomial, and the marginal beta-binomial model is more robust than the bivariate generalized linear mixed model under model misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta-analysis of case-control studies are conducted for illustration. Copyright © 2015 John Wiley & Sons, Ltd.

Sex differences in medico-legal action against doctors: a systematic review and meta-analysis.

PubMed

Unwin, Emily; Woolf, Katherine; Wadlow, Clare; Potts, Henry W W; Dacre, Jane

2015-08-13

The relationship between male sex and poor performance in doctors remains unclear, with high profile studies showing conflicting results. Nevertheless, it is an important first step towards understanding the causes of poor performance in doctors. This article aims to establish the robustness of the association between male sex and poor performance in doctors, internationally and over time. The electronic databases MEDLINE, EMBASE, and PsycINFO were searched from inception to January 2015. Backward and forward citation searching was performed. Journals that yielded the majority of the eligible articles and journals in the medical education field were electronically searched, along with the conference and poster abstracts from two of the largest international medical education conferences. Studies reporting original data, written in English or French, examining the association between sex and medico-legal action against doctors were included. Two reviewers independently extracted study characteristics and outcome data from the full texts of the studies meeting the eligibility criteria. Study quality was assessed using the Newcastle-Ottawa scale. A random effect meta-analysis model was used to summarize and assess the effect of doctors' sex on medico-legal action. Extracted outcomes included disciplinary action by a medical regulatory board, malpractice experience, referral to a medical regulatory body, complaints received by a healthcare complaints body, criminal cases, and medico-legal matter with a medical defence organisation. Overall, 32 reports examining the association between doctors' sex and medico-legal action were included in the systematic review (n=4,054,551), of which 27 found that male doctors were more likely to have experienced medico-legal action. 19 reports were included in the meta-analysis (n=3,794,486, including 20,666 cases). Results showed male doctors had nearly two and a half times the odds of being subject to medico-legal action than female doctors. Heterogeneity was present in all meta-analyses. Male doctors are more likely to have had experienced medico-legal actions compared to female doctors. This finding is robust internationally, across outcomes of varying severity, and over time.

Combining evidence from multiple electronic health care databases: performances of one-stage and two-stage meta-analysis in matched case-control studies.

PubMed

La Gamba, Fabiola; Corrao, Giovanni; Romio, Silvana; Sturkenboom, Miriam; Trifirò, Gianluca; Schink, Tania; de Ridder, Maria

2017-10-01

Clustering of patients in databases is usually ignored in one-stage meta-analysis of multi-database studies using matched case-control data. The aim of this study was to compare bias and efficiency of such a one-stage meta-analysis with a two-stage meta-analysis. First, we compared the approaches by generating matched case-control data under 5 simulated scenarios, built by varying: (1) the exposure-outcome association; (2) its variability among databases; (3) the confounding strength of one covariate on this association; (4) its variability; and (5) the (heterogeneous) confounding strength of two covariates. Second, we made the same comparison using empirical data from the ARITMO project, a multiple database study investigating the risk of ventricular arrhythmia following the use of medications with arrhythmogenic potential. In our study, we specifically investigated the effect of current use of promethazine. Bias increased for one-stage meta-analysis with increasing (1) between-database variance of exposure effect and (2) heterogeneous confounding generated by two covariates. The efficiency of one-stage meta-analysis was slightly lower than that of two-stage meta-analysis for the majority of investigated scenarios. Based on ARITMO data, there were no evident differences between one-stage (OR = 1.50, CI = [1.08; 2.08]) and two-stage (OR = 1.55, CI = [1.12; 2.16]) approaches. When the effect of interest is heterogeneous, a one-stage meta-analysis ignoring clustering gives biased estimates. Two-stage meta-analysis generates estimates at least as accurate and precise as one-stage meta-analysis. However, in a study using small databases and rare exposures and/or outcomes, a correct one-stage meta-analysis becomes essential. Copyright © 2017 John Wiley & Sons, Ltd.

SI-traceable and dynamic reference gas mixtures for water vapour at polar and high troposphere atmospheric levels

NASA Astrophysics Data System (ADS)

Guillevic, Myriam; Pascale, Céline; Mutter, Daniel; Wettstein, Sascha; Niederhauser, Bernhard

2017-04-01

In the framework of METAS' AtmoChem-ECV project, new facilities are currently being developed to generate reference gas mixtures for water vapour at concentrations measured in the high troposphere and polar regions, in the range 1-20 µmol/mol (ppm). The generation method is dynamic (the mixture is produced continuously over time) and SI-traceable (i.e. the amount of substance fraction in mole per mole is traceable to the definition of SI-units). The generation process is composed of three successive steps. The first step is to purify the matrix gas, nitrogen or synthetic air. Second, this matrix gas is spiked with the pure substance using a permeation technique: a permeation device contains a few grams of pure water in liquid form and loses it linearly over time by permeation through a membrane. In a third step, to reach the desired concentration, the first, high concentration mixture exiting the permeation chamber is then diluted with a chosen flow of matrix gas with one or two subsequent dilution steps. All flows are piloted by mass flow controllers. All parts in contact with the gas mixture are passivated using coated surfaces, to reduce adsorption/desorption processes as much as possible. The mixture can eventually be directly used to calibrate an analyser. The standard mixture produced by METAS' dynamic setup was injected into a chilled mirror from MBW Calibration AG, the designated institute for absolute humidity calibration in Switzerland. The used chilled mirror, model 373LX, is able to measure frost point and sample pressure and therefore calculate the water vapour concentration. This intercomparison of the two systems was performed in the range 4-18 ppm water vapour in synthetic air, at two different pressure levels, 1013.25 hPa and 2000 hPa. We present here METAS' dynamic setup, its uncertainty budget and the first results of the intercomparison with MBW's chilled mirror.

Model-driven meta-analyses for informing health care: a diabetes meta-analysis as an exemplar.

PubMed

Brown, Sharon A; Becker, Betsy Jane; García, Alexandra A; Brown, Adama; Ramírez, Gilbert

2015-04-01

A relatively novel type of meta-analysis, a model-driven meta-analysis, involves the quantitative synthesis of descriptive, correlational data and is useful for identifying key predictors of health outcomes and informing clinical guidelines. Few such meta-analyses have been conducted and thus, large bodies of research remain unsynthesized and uninterpreted for application in health care. We describe the unique challenges of conducting a model-driven meta-analysis, focusing primarily on issues related to locating a sample of published and unpublished primary studies, extracting and verifying descriptive and correlational data, and conducting analyses. A current meta-analysis of the research on predictors of key health outcomes in diabetes is used to illustrate our main points. © The Author(s) 2014.

MODEL-DRIVEN META-ANALYSES FOR INFORMING HEALTH CARE: A DIABETES META-ANALYSIS AS AN EXEMPLAR

PubMed Central

Brown, Sharon A.; Becker, Betsy Jane; García, Alexandra A.; Brown, Adama; Ramírez, Gilbert

2015-01-01

A relatively novel type of meta-analysis, a model-driven meta-analysis, involves the quantitative synthesis of descriptive, correlational data and is useful for identifying key predictors of health outcomes and informing clinical guidelines. Few such meta-analyses have been conducted and thus, large bodies of research remain unsynthesized and uninterpreted for application in health care. We describe the unique challenges of conducting a model-driven meta-analysis, focusing primarily on issues related to locating a sample of published and unpublished primary studies, extracting and verifying descriptive and correlational data, and conducting analyses. A current meta-analysis of the research on predictors of key health outcomes in diabetes is used to illustrate our main points. PMID:25142707

Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: a systematic review and meta-analysis.

PubMed

van der Feltz-Cornelis, Christina M; Nuyen, Jasper; Stoop, Corinne; Chan, Juliana; Jacobson, Alan M; Katon, Wayne; Snoek, Frank; Sartorius, Norman

2010-01-01

Comorbid depression in diabetes is highly prevalent, negatively impacting well-being and diabetes control. How depression in diabetes is best treated is unknown. This systematic review and meta-analysis aims to establish the effectiveness of existing anti-depressant therapies in diabetes. PubMed, Psycinfo, Embase and Cochrane library. Study eligibility criteria, participants, interventions: randomized controlled trials (RCTs) evaluating the outcome of treatment by psychotherapy, pharmacotherapy or collaborative care of depression in persons with Type 1 and Type 2 diabetes mellitus. risk of bias assessment; data extraction. Synthesis methods: data synthesis, random model meta analysis and publication bias analysis. Meta analysis of 14 RCTs with a total of 1724 patients show that treatment is effective in terms of reduction of depressive symptoms: -0.512; 95% CI -0.633 to -0.390. The combined effect of all interventions on clinical impact is moderate, -0.370; 95% CI -0.470 to -0.271; it is large for psychotherapeutic interventions that are often combined with diabetes self management: -0.581; 95% CI -0.770 to -0.391, n=310 and moderate for pharmacological treatment: -0.467; 95% CI -0.665 to -0.270, n=281. Delivery of collaborative care, which provided a stepped care intervention with a choice of starting with psychotherapy or pharmacotherapy, to a primary care population, yielded an effect size of -0.292; 95% CI -0.429 to -0.155, n=1133; indicating the effect size that can be attained on a population scale. Pharmacotherapy and collaborative care aimed at and succeeded in the reduction of depressive symptoms but, apart from sertraline, had no effect on glycemic control. amongst others, the number of RCTs is small. The treatment of depression in people with diabetes is a necessary step, but improvement of the general medical condition including glycemic control is likely to require simultaneous attention to both conditions. Further research is needed. Copyright 2010 Elsevier Inc. All rights reserved.

Quantifying variability in removal efficiencies of chemicals in activated sludge wastewater treatment plants - a meta-analytical approach.

PubMed

Douziech, Mélanie; Conesa, Irene Rosique; Benítez-López, Ana; Franco, Antonio; Huijbregts, Mark; van Zelm, Rosalie

2018-01-24

Large variations in removal efficiencies (REs) of chemicals have been reported for monitoring studies of activated sludge wastewater treatment plants (WWTPs). In this work, we conducted a meta-analysis on REs (1539 data points) for a set of 209 chemicals consisting of fragrances, surfactants, and pharmaceuticals in order to assess the drivers of the variability relating to inherent properties of the chemicals and operational parameters of activated sludge WWTPs. For a reduced dataset (n = 542), we developed a mixed-effect model (meta-regression) to explore the observed variability in REs for the chemicals using three chemical specific factors and four WWTP-related parameters. The overall removal efficiency of the set of chemicals was 82.1% (95% CI 75.2-87.1%, N = 1539). Our model accounted for 17% of the total variability in REs, while the process-based model SimpleTreat did not perform better than the average of the measured REs. We identified that, after accounting for other factors potentially influencing RE, readily biodegradable compounds were better removed than non-readily biodegradable ones. Further, we showed that REs increased with increasing sludge retention times (SRTs), especially for non-readily biodegradable compounds. Finally, our model highlighted a decrease in RE with increasing K OC . The counterintuitive relationship to K OC stresses the need for a better understanding of electrochemical interactions influencing the RE of ionisable chemicals. In addition, we highlighted the need to improve the modelling of chemicals that undergo deconjugation when predicting RE. Our meta-analysis represents a first step in better explaining the observed variability in measured REs of chemicals. It can be of particular help to prioritize the improvements required in existing process-based models to predict removal efficiencies of chemicals in WWTPs.

Management of Listeria monocytogenes in fermented sausages using the Food Safety Objective concept underpinned by stochastic modeling and meta-analysis.

PubMed

Mataragas, M; Alessandria, V; Rantsiou, K; Cocolin, L

2015-08-01

In the present work, a demonstration is made on how the risk from the presence of Listeria monocytogenes in fermented sausages can be managed using the concept of Food Safety Objective (FSO) aided by stochastic modeling (Bayesian analysis and Monte Carlo simulation) and meta-analysis. For this purpose, the ICMSF equation was used, which combines the initial level (H0) of the hazard and its subsequent reduction (ΣR) and/or increase (ΣI) along the production chain. Each element of the equation was described by a distribution to investigate the effect not only of the level of the hazard, but also the effect of the accompanying variability. The distribution of each element was determined by Bayesian modeling (H0) and meta-analysis (ΣR and ΣI). The output was a normal distribution N(-5.36, 2.56) (log cfu/g) from which the percentage of the non-conforming products, i.e. the fraction above the FSO of 2 log cfu/g, was estimated at 0.202%. Different control measures were examined such as lowering initial L. monocytogenes level and inclusion of an additional killing step along the process resulting in reduction of the non-conforming products from 0.195% to 0.003% based on the mean and/or square-root change of the normal distribution, and 0.001%, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lipid profile changes after pomegranate consumption: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Sahebkar, Amirhossein; Simental-Mendía, Luis E; Giorgini, Paolo; Ferri, Claudio; Grassi, Davide

2016-10-15

Transport of oxidized low-density lipoprotein across the endothelium into the artery wall is considered a fundamental priming step for the atherosclerotic process. Recent studies reported potential therapeutic effects of micronutrients found in natural products, indicating positive applications for controlling the pathogenesis of chronic cardiovascular disease driven by cardiovascular risk factors and oxidative stress. A particular attention has been recently addressed to pomegranate; however findings of clinical studies have been contrasting. To evaluate the effects of pomegranate consumption on plasma lipid concentrations through a systematic review and meta-analysis of randomized controlled trials (RCTs). The study was designed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Scopus and Medline databases were searched to identify randomized placebo-controlled trials investigating the impact of pomegranate on plasma lipid concentrations. A fixed-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes. A total of 545 individuals were recruited from the 12 RCTs. Fixed-effect meta-analysis of data from 12 RCTs (13 treatment arms) did not show any significant effect of pomegranate consumption on plasma lipid concentrations. The results of meta-regression did not suggest any significant association between duration of supplementation and impact of pomegranate on total cholesterol and HDL-C, while an inverse association was found with changes in triglycerides levels (slope: -1.07; 95% CI: -2.03 to -0.11; p = 0.029). There was no association between the amount of pomegranate juice consumed per day and respective changes in plasma total cholesterol, LDL-C, HDL-C and triglycerides. The present meta-analysis of RCTs did not suggest any effect of pomegranate consumption on lipid profile in human. Copyright © 2016. Published by Elsevier GmbH.

An Optimization-Driven Analysis Pipeline to Uncover Biomarkers and Signaling Paths: Cervix Cancer.

PubMed

Lorenzo, Enery; Camacho-Caceres, Katia; Ropelewski, Alexander J; Rosas, Juan; Ortiz-Mojer, Michael; Perez-Marty, Lynn; Irizarry, Juan; Gonzalez, Valerie; Rodríguez, Jesús A; Cabrera-Rios, Mauricio; Isaza, Clara

2015-06-01

Establishing how a series of potentially important genes might relate to each other is relevant to understand the origin and evolution of illnesses, such as cancer. High-throughput biological experiments have played a critical role in providing information in this regard. A special challenge, however, is that of trying to conciliate information from separate microarray experiments to build a potential genetic signaling path. This work proposes a two-step analysis pipeline, based on optimization, to approach meta-analysis aiming to build a proxy for a genetic signaling path.

Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis.

PubMed

Li, Chen; Yichao, Jin; Jiaxin, Lin; Yueting, Zhang; Qin, Lu; Tonghua, Yang

2015-01-01

Reported evidence supports a role for methylenetetrahydrofolate reductase (MTHFR) in the risk of chronic myelogenous leykemia (CML). However, these reports arrived at non-conclusive and even conflicting results regarding the association between two common MTHFR polymorphisms (C677T and A1298C) and CML risk. Thus, a meta-analysis was carried out to clarify a more precise association between these two polymorphisms and the CML risk by updating the available publications. Pooled odds ratios (OR) with corresponding 95% confidence interval (95% CI) and stratification analysis were performed to estimate the relationship between MTHFR polymorphisms and the risk of CML under different genetic comparison models. Data from the meta-analysis showed no significant association between MTHFR C677T polymorphism and CML risk. However, significant associations were found between MTHFR A1298C variants and CML risk under homozygous comparison model (CC vs AA, OR=1.62, 95% CI=1.11-2.36, p=0.01) and dominant comparison model (CC+AC vs AA, OR=1.68, 95% CI=1.17-2.43, p=0.005) in overall population; especially more obvious impacts were noticed for Asian populations in subgroup analysis for homozygous model (CC vs AA, OR=2.00, 95% CI=1.25-3.21, p=0.004) and dominant model (CC+AC vs AA, OR=2.49, 95% CI=1.42-4.36, p=0.001), but this did not apply in Caucasian populations. The results of this meta-analysis suggested no significant association between MTHFR C677T polymorphism and CML risk, while an increased CML risk was noticed for 1298C variant carriers, especially in Asian populations but not in Caucasian populations, which suggested ethnicity differences between MTHFR A1298C polymorphisms and risk of CML.

A META-COMPOSITE SOFTWARE DEVELOPMENT APPROACH FOR TRANSLATIONAL RESEARCH

PubMed Central

Sadasivam, Rajani S.; Tanik, Murat M.

2013-01-01

Translational researchers conduct research in a highly data-intensive and continuously changing environment and need to use multiple, disparate tools to achieve their goals. These researchers would greatly benefit from meta-composite software development or the ability to continuously compose and recompose tools together in response to their ever-changing needs. However, the available tools are largely disconnected, and current software approaches are inefficient and ineffective in their support for meta-composite software development. Building on the composite services development approach, the de facto standard for developing integrated software systems, we propose a concept-map and agent-based meta-composite software development approach. A crucial step in composite services development is the modeling of users’ needs as processes, which can then be specified in an executable format for system composition. We have two key innovations. First, our approach allows researchers (who understand their needs best) instead of technicians to take a leadership role in the development of process models, reducing inefficiencies and errors. A second innovation is that our approach also allows for modeling of complex user interactions as part of the process, overcoming the technical limitations of current tools. We demonstrate the feasibility of our approach using a real-world translational research use case. We also present results of usability studies evaluating our approach for future refinements. PMID:23504436

A meta-composite software development approach for translational research.

PubMed

Sadasivam, Rajani S; Tanik, Murat M

2013-06-01

Translational researchers conduct research in a highly data-intensive and continuously changing environment and need to use multiple, disparate tools to achieve their goals. These researchers would greatly benefit from meta-composite software development or the ability to continuously compose and recompose tools together in response to their ever-changing needs. However, the available tools are largely disconnected, and current software approaches are inefficient and ineffective in their support for meta-composite software development. Building on the composite services development approach, the de facto standard for developing integrated software systems, we propose a concept-map and agent-based meta-composite software development approach. A crucial step in composite services development is the modeling of users' needs as processes, which can then be specified in an executable format for system composition. We have two key innovations. First, our approach allows researchers (who understand their needs best) instead of technicians to take a leadership role in the development of process models, reducing inefficiencies and errors. A second innovation is that our approach also allows for modeling of complex user interactions as part of the process, overcoming the technical limitations of current tools. We demonstrate the feasibility of our approach using a real-world translational research use case. We also present results of usability studies evaluating our approach for future refinements.

SCOPA and META-SCOPA: software for the analysis and aggregation of genome-wide association studies of multiple correlated phenotypes.

PubMed

Mägi, Reedik; Suleimanov, Yury V; Clarke, Geraldine M; Kaakinen, Marika; Fischer, Krista; Prokopenko, Inga; Morris, Andrew P

2017-01-11

Genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) have been successful in identifying loci contributing genetic effects to a wide range of complex human diseases and quantitative traits. The traditional approach to GWAS analysis is to consider each phenotype separately, despite the fact that many diseases and quantitative traits are correlated with each other, and often measured in the same sample of individuals. Multivariate analyses of correlated phenotypes have been demonstrated, by simulation, to increase power to detect association with SNPs, and thus may enable improved detection of novel loci contributing to diseases and quantitative traits. We have developed the SCOPA software to enable GWAS analysis of multiple correlated phenotypes. The software implements "reverse regression" methodology, which treats the genotype of an individual at a SNP as the outcome and the phenotypes as predictors in a general linear model. SCOPA can be applied to quantitative traits and categorical phenotypes, and can accommodate imputed genotypes under a dosage model. The accompanying META-SCOPA software enables meta-analysis of association summary statistics from SCOPA across GWAS. Application of SCOPA to two GWAS of high-and low-density lipoprotein cholesterol, triglycerides and body mass index, and subsequent meta-analysis with META-SCOPA, highlighted stronger association signals than univariate phenotype analysis at established lipid and obesity loci. The META-SCOPA meta-analysis also revealed a novel signal of association at genome-wide significance for triglycerides mapping to GPC5 (lead SNP rs71427535, p = 1.1x10 -8 ), which has not been reported in previous large-scale GWAS of lipid traits. The SCOPA and META-SCOPA software enable discovery and dissection of multiple phenotype association signals through implementation of a powerful reverse regression approach.

Prevalence of anemia among school-age children in Ethiopia: a systematic review and meta-analysis.

PubMed

Tezera, Robel; Sahile, Zekariyas; Yilma, Delelegn; Misganaw, Equilnet; Mulu, Ermiyas

2018-05-24

Anemia continued to become a major public health problem in developing nations including Ethiopia. Especially, school children are more vulnerable for anemia and consequences of anemia. Generating accurate epidemiological data on anemia in school children is an important step for health policy maker. There are limited evidences on anemia prevalence in school-age children in Ethiopia. This study aimed to synthesize the pooled prevalence of anemia in school-age children in Ethiopia. This systematic review and meta-analysis was followed the PRISMA guidelines. Comprehensive searched was conducted in PubMed/MEDLINE, Cochrane Library, Google Scholar, HINARI, and Ethiopian Journal of Health Development for studies published before 2016, supplemented by manual searches to identify relevant studies. Two review authors independently selected studies, extracted data, and assessed quality of studies. The Cochrane Q test and I 2 test statistic were used to test heterogeneity through studies. The overall prevalence was calculated using random-effects model of DerSimonian-Laird method. From 831 obtained studies, 13 articles included in the meta-analysis. The pooled prevalence of anemia among school children in Ethiopia was 23% (95% CI 18-28%). The prevalence of anemia in male and female school-age children was 27% (95% CI 20 and 34%) and 24% (95% CI 18 and 30%), respectively. This study found that prevalence of anemia was a moderate public health problem in school children. Due to the complications of anemia for school children, preventative planning and control of anemia among school children in Ethiopia is necessary.

Methodological Standards for Meta-Analyses and Qualitative Systematic Reviews of Cardiac Prevention and Treatment Studies: A Scientific Statement From the American Heart Association.

PubMed

Rao, Goutham; Lopez-Jimenez, Francisco; Boyd, Jack; D'Amico, Frank; Durant, Nefertiti H; Hlatky, Mark A; Howard, George; Kirley, Katherine; Masi, Christopher; Powell-Wiley, Tiffany M; Solomonides, Anthony E; West, Colin P; Wessel, Jennifer

2017-09-05

Meta-analyses are becoming increasingly popular, especially in the fields of cardiovascular disease prevention and treatment. They are often considered to be a reliable source of evidence for making healthcare decisions. Unfortunately, problems among meta-analyses such as the misapplication and misinterpretation of statistical methods and tests are long-standing and widespread. The purposes of this statement are to review key steps in the development of a meta-analysis and to provide recommendations that will be useful for carrying out meta-analyses and for readers and journal editors, who must interpret the findings and gauge methodological quality. To make the statement practical and accessible, detailed descriptions of statistical methods have been omitted. Based on a survey of cardiovascular meta-analyses, published literature on methodology, expert consultation, and consensus among the writing group, key recommendations are provided. Recommendations reinforce several current practices, including protocol registration; comprehensive search strategies; methods for data extraction and abstraction; methods for identifying, measuring, and dealing with heterogeneity; and statistical methods for pooling results. Other practices should be discontinued, including the use of levels of evidence and evidence hierarchies to gauge the value and impact of different study designs (including meta-analyses) and the use of structured tools to assess the quality of studies to be included in a meta-analysis. We also recommend choosing a pooling model for conventional meta-analyses (fixed effect or random effects) on the basis of clinical and methodological similarities among studies to be included, rather than the results of a test for statistical heterogeneity. © 2017 American Heart Association, Inc.

Handling incomplete correlated continuous and binary outcomes in meta-analysis of individual participant data.

PubMed

Gomes, Manuel; Hatfield, Laura; Normand, Sharon-Lise

2016-09-20

Meta-analysis of individual participant data (IPD) is increasingly utilised to improve the estimation of treatment effects, particularly among different participant subgroups. An important concern in IPD meta-analysis relates to partially or completely missing outcomes for some studies, a problem exacerbated when interest is on multiple discrete and continuous outcomes. When leveraging information from incomplete correlated outcomes across studies, the fully observed outcomes may provide important information about the incompleteness of the other outcomes. In this paper, we compare two models for handling incomplete continuous and binary outcomes in IPD meta-analysis: a joint hierarchical model and a sequence of full conditional mixed models. We illustrate how these approaches incorporate the correlation across the multiple outcomes and the between-study heterogeneity when addressing the missing data. Simulations characterise the performance of the methods across a range of scenarios which differ according to the proportion and type of missingness, strength of correlation between outcomes and the number of studies. The joint model provided confidence interval coverage consistently closer to nominal levels and lower mean squared error compared with the fully conditional approach across the scenarios considered. Methods are illustrated in a meta-analysis of randomised controlled trials comparing the effectiveness of implantable cardioverter-defibrillator devices alone to implantable cardioverter-defibrillator combined with cardiac resynchronisation therapy for treating patients with chronic heart failure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

PubMed

Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

2015-07-30

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Meta-analysis of gene expression patterns in animal models of prenatal alcohol exposure suggests role for protein synthesis inhibition and chromatin remodeling

PubMed Central

Rogic, Sanja; Wong, Albertina; Pavlidis, Paul

2017-01-01

Background Prenatal alcohol exposure (PAE) can result in an array of morphological, behavioural and neurobiological deficits that can range in their severity. Despite extensive research in the field and a significant progress made, especially in understanding the range of possible malformations and neurobehavioral abnormalities, the molecular mechanisms of alcohol responses in development are still not well understood. There have been multiple transcriptomic studies looking at the changes in gene expression after PAE in animal models, however there is a limited apparent consensus among the reported findings. In an effort to address this issue, we performed a comprehensive re-analysis and meta-analysis of all suitable, publically available expression data sets. Methods We assembled ten microarray data sets of gene expression after PAE in mouse and rat models consisting of samples from a total of 63 ethanol-exposed and 80 control animals. We re-analyzed each data set for differential expression and then used the results to perform meta-analyses considering all data sets together or grouping them by time or duration of exposure (pre- and post-natal, acute and chronic, respectively). We performed network and Gene Ontology enrichment analysis to further characterize the identified signatures. Results For each sub-analysis we identified signatures of differential expressed genes that show support from multiple studies. Overall, the changes in gene expression were more extensive after acute ethanol treatment during prenatal development than in other models. Considering the analysis of all the data together, we identified a robust core signature of 104 genes down-regulated after PAE, with no up-regulated genes. Functional analysis reveals over-representation of genes involved in protein synthesis, mRNA splicing and chromatin organization. Conclusions Our meta-analysis shows that existing studies, despite superficial dissimilarity in findings, share features that allow us to identify a common core signature set of transcriptome changes in PAE. This is an important step to identifying the biological processes that underlie the etiology of FASD. PMID:26996386

A method for meta-analysis of epidemiological studies.

PubMed

Einarson, T R; Leeder, J S; Koren, G

1988-10-01

This article presents a stepwise approach for conducting a meta-analysis of epidemiological studies based on proposed guidelines. This systematic method is recommended for practitioners evaluating epidemiological studies in the literature to arrive at an overall quantitative estimate of the impact of a treatment. Bendectin is used as an illustrative example. Meta-analysts should establish a priori the purpose of the analysis and a complete protocol. This protocol should be adhered to, and all steps performed should be recorded in detail. To aid in developing such a protocol, we present methods the researcher can use to perform each of 22 steps in six major areas. The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans. The overall summary odds ratio was 1.01 (chi 2 = 0.05, p = 0.815) with a 95 percent confidence interval of 0.66-1.55. When the studies were separated according to study type, the summary odds ratio for cohort studies was 0.95 with a 95 percent confidence interval of 0.62-1.45. For case-control studies, the summary odds ratio was 1.27 with a 95 percent confidence interval of 0.83-1.94. The corresponding chi-square values were not statistically significant at the p = 0.05 level.

Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis

PubMed Central

Khaing, Win; Vallibhakara, Sakda Arj-Ong; Tantrakul, Visasiri; Vallibhakara, Orawin; Rattanasiri, Sasivimol; McEvoy, Mark; Attia, John; Thakkinstian, Ammarin

2017-01-01

Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings. PMID:29057843

Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis.

PubMed

Khaing, Win; Vallibhakara, Sakda Arj-Ong; Tantrakul, Visasiri; Vallibhakara, Orawin; Rattanasiri, Sasivimol; McEvoy, Mark; Attia, John; Thakkinstian, Ammarin

2017-10-18

Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings.

Sequential change detection and monitoring of temporal trends in random-effects meta-analysis.

PubMed

Dogo, Samson Henry; Clark, Allan; Kulinskaya, Elena

2017-06-01

Temporal changes in magnitude of effect sizes reported in many areas of research are a threat to the credibility of the results and conclusions of meta-analysis. Numerous sequential methods for meta-analysis have been proposed to detect changes and monitor trends in effect sizes so that meta-analysis can be updated when necessary and interpreted based on the time it was conducted. The difficulties of sequential meta-analysis under the random-effects model are caused by dependencies in increments introduced by the estimation of the heterogeneity parameter τ 2 . In this paper, we propose the use of a retrospective cumulative sum (CUSUM)-type test with bootstrap critical values. This method allows retrospective analysis of the past trajectory of cumulative effects in random-effects meta-analysis and its visualization on a chart similar to CUSUM chart. Simulation results show that the new method demonstrates good control of Type I error regardless of the number or size of the studies and the amount of heterogeneity. Application of the new method is illustrated on two examples of medical meta-analyses. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

Multivariate Methods for Meta-Analysis of Genetic Association Studies.

PubMed

Dimou, Niki L; Pantavou, Katerina G; Braliou, Georgia G; Bagos, Pantelis G

2018-01-01

Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.

Meta-analytical synthesis of regression coefficients under different categorization scheme of continuous covariates.

PubMed

Yoneoka, Daisuke; Henmi, Masayuki

2017-11-30

Recently, the number of clinical prediction models sharing the same regression task has increased in the medical literature. However, evidence synthesis methodologies that use the results of these regression models have not been sufficiently studied, particularly in meta-analysis settings where only regression coefficients are available. One of the difficulties lies in the differences between the categorization schemes of continuous covariates across different studies. In general, categorization methods using cutoff values are study specific across available models, even if they focus on the same covariates of interest. Differences in the categorization of covariates could lead to serious bias in the estimated regression coefficients and thus in subsequent syntheses. To tackle this issue, we developed synthesis methods for linear regression models with different categorization schemes of covariates. A 2-step approach to aggregate the regression coefficient estimates is proposed. The first step is to estimate the joint distribution of covariates by introducing a latent sampling distribution, which uses one set of individual participant data to estimate the marginal distribution of covariates with categorization. The second step is to use a nonlinear mixed-effects model with correction terms for the bias due to categorization to estimate the overall regression coefficients. Especially in terms of precision, numerical simulations show that our approach outperforms conventional methods, which only use studies with common covariates or ignore the differences between categorization schemes. The method developed in this study is also applied to a series of WHO epidemiologic studies on white blood cell counts. Copyright © 2017 John Wiley & Sons, Ltd.

Methodological quality evaluation of systematic reviews or meta-analyses on ERCC1 in non-small cell lung cancer: a systematic review.

PubMed

Tao, Huan; Zhang, Yueyuan; Li, Qian; Chen, Jin

2017-11-01

To assess the methodological quality of systematic reviews (SRs) or meta-analysis concerning the predictive value of ERCC1 in platinum chemotherapy of non-small cell lung cancer. We searched the PubMed, EMbase, Cochrane library, international prospective register of systematic reviews, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Wan Fang and VIP database for SRs or meta-analysis. The methodological quality of included literatures was evaluated by risk of bias in systematic review (ROBIS) scale. Nineteen eligible SRs/meta-analysis were included. The most frequently searched databases were EMbase (74%), PubMed, Medline and CNKI. Fifteen SRs did additional retrieval manually, but none of them retrieved the registration platform. 47% described the two-reviewers model in the screening for eligible original articles, and seven SRs described the two reviewers to extract data. In methodological quality assessment, inter-rater reliability Kappa was 0.87 between two reviewers. Research question were well related to all SRs in phase 1 and the eligibility criteria was suitable for each SR, and rated as 'low' risk bias. But the 'high' risk bias existed in all the SRs regarding methods used to identify and/or select studies, and data collection and study appraisal. More than two-third of SRs or meta-analysis were finished with high risk of bias in the synthesis, findings and the final phase. The study demonstrated poor methodological quality of SRs/meta-analysis assessing the predictive value of ERCC1 in chemotherapy among the NSCLC patients, especially the high performance bias. Registration or publishing the protocol is recommended in future research.

Meta-analysis of diagnostic accuracy studies accounting for disease prevalence: alternative parameterizations and model selection.

PubMed

Chu, Haitao; Nie, Lei; Cole, Stephen R; Poole, Charles

2009-08-15

In a meta-analysis of diagnostic accuracy studies, the sensitivities and specificities of a diagnostic test may depend on the disease prevalence since the severity and definition of disease may differ from study to study due to the design and the population considered. In this paper, we extend the bivariate nonlinear random effects model on sensitivities and specificities to jointly model the disease prevalence, sensitivities and specificities using trivariate nonlinear random-effects models. Furthermore, as an alternative parameterization, we also propose jointly modeling the test prevalence and the predictive values, which reflect the clinical utility of a diagnostic test. These models allow investigators to study the complex relationship among the disease prevalence, sensitivities and specificities; or among test prevalence and the predictive values, which can reveal hidden information about test performance. We illustrate the proposed two approaches by reanalyzing the data from a meta-analysis of radiological evaluation of lymph node metastases in patients with cervical cancer and a simulation study. The latter illustrates the importance of carefully choosing an appropriate normality assumption for the disease prevalence, sensitivities and specificities, or the test prevalence and the predictive values. In practice, it is recommended to use model selection techniques to identify a best-fitting model for making statistical inference. In summary, the proposed trivariate random effects models are novel and can be very useful in practice for meta-analysis of diagnostic accuracy studies. Copyright 2009 John Wiley & Sons, Ltd.

A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence.

PubMed

Nikoloulopoulos, Aristidis K

2017-10-01

A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality.

Contrast use in relation to the arterial access site for percutaneous coronary intervention: A comprehensive meta-analysis of randomized trials

PubMed Central

Shah, Rahman; Mattox, Anthony; Khan, M Rehan; Berzingi, Chalak; Rashid, Abdul

2017-01-01

AIM To compare the amount of contrast used during percutaneous coronary intervention (PCI) via trans-radial access (TRA) vs trans-femoral access (TFA). METHODS Scientific databases and websites were searched for:randomizedcontrolledtrials (RCTs). Data were extracted by two independent reviewers and was summarized as the weighted mean difference (WMD) of contrast used with a 95%CI using a random-effects model. RESULTS The meta-analysis included 13 RCTs with a total of 3165 patients. There was no difference between the two strategies in the amount of contrast used (WMD = - 0.65 mL, 95%CI: -10.94-9.46 mL; P = 0.901). CONCLUSION This meta-analysis shows that in patients undergoing PCI, the amount of contrast volume used was not different between TRA and TFA. PMID:28515857

Spatial Bayesian Latent Factor Regression Modeling of Coordinate-based Meta-analysis Data

PubMed Central

Montagna, Silvia; Wager, Tor; Barrett, Lisa Feldman; Johnson, Timothy D.; Nichols, Thomas E.

2017-01-01

Summary Now over 20 years old, functional MRI (fMRI) has a large and growing literature that is best synthesised with meta-analytic tools. As most authors do not share image data, only the peak activation coordinates (foci) reported in the paper are available for Coordinate-Based Meta-Analysis (CBMA). Neuroimaging meta-analysis is used to 1) identify areas of consistent activation; and 2) build a predictive model of task type or cognitive process for new studies (reverse inference). To simultaneously address these aims, we propose a Bayesian point process hierarchical model for CBMA. We model the foci from each study as a doubly stochastic Poisson process, where the study-specific log intensity function is characterised as a linear combination of a high-dimensional basis set. A sparse representation of the intensities is guaranteed through latent factor modeling of the basis coefficients. Within our framework, it is also possible to account for the effect of study-level covariates (meta-regression), significantly expanding the capabilities of the current neuroimaging meta-analysis methods available. We apply our methodology to synthetic data and neuroimaging meta-analysis datasets. PMID:28498564

The predictive validity of the MCAT for medical school performance and medical board licensing examinations: a meta-analysis of the published research.

PubMed

Donnon, Tyrone; Paolucci, Elizabeth Oddone; Violato, Claudio

2007-01-01

To conduct a meta-analysis of published studies to determine the predictive validity of the MCAT on medical school performance and medical board licensing examinations. The authors included all peer-reviewed published studies reporting empirical data on the relationship between MCAT scores and medical school performance or medical board licensing exam measures. Moderator variables, participant characteristics, and medical school performance/medical board licensing exam measures were extracted and reviewed separately by three reviewers using a standardized protocol. Medical school performance measures from 11 studies and medical board licensing examinations from 18 studies, for a total of 23 studies, were selected. A random-effects model meta-analysis of weighted effects sizes (r) resulted in (1) a predictive validity coefficient for the MCAT in the preclinical years of r = 0.39 (95% confidence interval [CI], 0.21-0.54) and on the USMLE Step 1 of r = 0.60 (95% CI, 0.50-0.67); and (2) the biological sciences subtest as the best predictor of medical school performance in the preclinical years (r = 0.32 95% CI, 0.21-0.42) and on the USMLE Step 1 (r = 0.48 95% CI, 0.41-0.54). The predictive validity of the MCAT ranges from small to medium for both medical school performance and medical board licensing exam measures. The medical profession is challenged to develop screening and selection criteria with improved validity that can supplement the MCAT as an important criterion for admission to medical schools.

Spontaneous Meta-Arithmetic as a First Step toward School Algebra

ERIC Educational Resources Information Center

Caspi, Shai; Sfard, Anna

2012-01-01

Taking as the point of departure the vision of school algebra as a formalized meta-discourse of arithmetic, we have been following five pairs of 7th grade students as they progress in algebraic discourse during 24 months, from their informal algebraic talk to the formal algebraic discourse, as taught in school. Our analysis follows changes that…

Human performance on the temporal bisection task.

PubMed

Kopec, Charles D; Brody, Carlos D

2010-12-01

The perception and processing of temporal information are tasks the brain must continuously perform. These include measuring the duration of stimuli, storing duration information in memory, recalling such memories, and comparing two durations. How the brain accomplishes these tasks, however, is still open for debate. The temporal bisection task, which requires subjects to compare temporal stimuli to durations held in memory, is perfectly suited to address these questions. Here we perform a meta-analysis of human performance on the temporal bisection task collected from 148 experiments spread across 18 independent studies. With this expanded data set we are able to show that human performance on this task contains a number of significant peculiarities, which in total no single model yet proposed has been able to explain. Here we present a simple 2-step decision model that is capable of explaining all the idiosyncrasies seen in the data. Copyright © 2010 Elsevier Inc. All rights reserved.

Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases.

PubMed

Friede, Tim; Röver, Christian; Wandel, Simon; Neuenschwander, Beat

2017-07-01

Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes. © 2016 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-monitoring to increase physical activity in patients with cardiovascular disease: a systematic review and meta-analysis.

PubMed

Kanejima, Yuji; Kitamura, Masahiro; Izawa, Kazuhiro P

2018-04-30

It is important to encourage physical activity in patients with cardiovascular disease (CVD), and self-monitoring is considered to contribute to increased physical activity. However, the effects of self-monitoring on CVD patients remain to be established. In this study, we examined the influence of self-monitoring on physical activity of patients with CVD via a systematic review and meta-analysis. Screening of randomized controlled trials only was undertaken twice on PubMed (date of appraisal: August 29, 2017). The inclusion criteria included outpatients with CVD, interventions for them, daily step counts as physical activity included in the outcome, and self-monitoring included in the intervention. Assessments of the risk of bias and meta-analysis in relation to the mean change of daily step counts were conducted to verify the effects of self-monitoring. From 205 studies retrieved on PubMed, six studies were included, with the oldest study published in 2005. Participants included 693 patients of whom 541 patients completed each study program. Their mean age was 60.8 years, and the ratio of men was 79.6%. From these 6 studies, a meta-analysis was conducted with 269 patients of 4 studies including only RCTs with step counts in the intervention group and the control group, and self-monitoring significantly increased physical activity (95% confidence interval, 1916-3090 steps per day, p < 0.05). The average intervention period was about 5 months. Moreover, four studies involved intervention via the internet, and five studies confirmed the use of self-monitoring combined with other behavior change techniques. The results suggest that self-monitoring of physical activity by patients with CVD has a significantly positive effect on their improvement. Moreover, the trend toward self-monitoring combined with setting counseling and activity goals, and increased intervention via the internet, may lead to the future development and spread of self-monitoring for CVD patients.

Statistical Test of Expression Pattern (STEPath): a new strategy to integrate gene expression data with genomic information in individual and meta-analysis studies.

PubMed

Martini, Paolo; Risso, Davide; Sales, Gabriele; Romualdi, Chiara; Lanfranchi, Gerolamo; Cagnin, Stefano

2011-04-11

In the last decades, microarray technology has spread, leading to a dramatic increase of publicly available datasets. The first statistical tools developed were focused on the identification of significant differentially expressed genes. Later, researchers moved toward the systematic integration of gene expression profiles with additional biological information, such as chromosomal location, ontological annotations or sequence features. The analysis of gene expression linked to physical location of genes on chromosomes allows the identification of transcriptionally imbalanced regions, while, Gene Set Analysis focuses on the detection of coordinated changes in transcriptional levels among sets of biologically related genes. In this field, meta-analysis offers the possibility to compare different studies, addressing the same biological question to fully exploit public gene expression datasets. We describe STEPath, a method that starts from gene expression profiles and integrates the analysis of imbalanced region as an a priori step before performing gene set analysis. The application of STEPath in individual studies produced gene set scores weighted by chromosomal activation. As a final step, we propose a way to compare these scores across different studies (meta-analysis) on related biological issues. One complication with meta-analysis is batch effects, which occur because molecular measurements are affected by laboratory conditions, reagent lots and personnel differences. Major problems occur when batch effects are correlated with an outcome of interest and lead to incorrect conclusions. We evaluated the power of combining chromosome mapping and gene set enrichment analysis, performing the analysis on a dataset of leukaemia (example of individual study) and on a dataset of skeletal muscle diseases (meta-analysis approach). In leukaemia, we identified the Hox gene set, a gene set closely related to the pathology that other algorithms of gene set analysis do not identify, while the meta-analysis approach on muscular disease discriminates between related pathologies and correlates similar ones from different studies. STEPath is a new method that integrates gene expression profiles, genomic co-expressed regions and the information about the biological function of genes. The usage of the STEPath-computed gene set scores overcomes batch effects in the meta-analysis approaches allowing the direct comparison of different pathologies and different studies on a gene set activation level.

A guide to understanding meta-analysis.

PubMed

Israel, Heidi; Richter, Randy R

2011-07-01

With the focus on evidence-based practice in healthcare, a well-conducted systematic review that includes a meta-analysis where indicated represents a high level of evidence for treatment effectiveness. The purpose of this commentary is to assist clinicians in understanding meta-analysis as a statistical tool using both published articles and explanations of components of the technique. We describe what meta-analysis is, what heterogeneity is, and how it affects meta-analysis, effect size, the modeling techniques of meta-analysis, and strengths and weaknesses of meta-analysis. Common components like forest plot interpretation, software that may be used, special cases for meta-analysis, such as subgroup analysis, individual patient data, and meta-regression, and a discussion of criticisms, are included.

Steps to an Ecology of Fear: Advanced Curriculum for Fearlessness. Technical Paper No. 38

ERIC Educational Resources Information Center

Fisher, R. Michael

2012-01-01

The author outlines a unique integral transdisciplinary theory (model, map) for studying four meta-motivations universal to all living systems. Within this theory are four primary principles to make the whole integral basis for understanding motivation and all that it determines in perception, thinking, feelings, actions. The four meta-motivations…

Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews

PubMed Central

Turner, Rebecca M; Davey, Jonathan; Clarke, Mike J; Thompson, Simon G; Higgins, Julian PT

2012-01-01

Background Many meta-analyses contain only a small number of studies, which makes it difficult to estimate the extent of between-study heterogeneity. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, and offers advantages over conventional random-effects meta-analysis. To assist in this, we provide empirical evidence on the likely extent of heterogeneity in particular areas of health care. Methods Our analyses included 14 886 meta-analyses from the Cochrane Database of Systematic Reviews. We classified each meta-analysis according to the type of outcome, type of intervention comparison and medical specialty. By modelling the study data from all meta-analyses simultaneously, using the log odds ratio scale, we investigated the impact of meta-analysis characteristics on the underlying between-study heterogeneity variance. Predictive distributions were obtained for the heterogeneity expected in future meta-analyses. Results Between-study heterogeneity variances for meta-analyses in which the outcome was all-cause mortality were found to be on average 17% (95% CI 10–26) of variances for other outcomes. In meta-analyses comparing two active pharmacological interventions, heterogeneity was on average 75% (95% CI 58–95) of variances for non-pharmacological interventions. Meta-analysis size was found to have only a small effect on heterogeneity. Predictive distributions are presented for nine different settings, defined by type of outcome and type of intervention comparison. For example, for a planned meta-analysis comparing a pharmacological intervention against placebo or control with a subjectively measured outcome, the predictive distribution for heterogeneity is a log-normal (−2.13, 1.582) distribution, which has a median value of 0.12. In an example of meta-analysis of six studies, incorporating external evidence led to a smaller heterogeneity estimate and a narrower confidence interval for the combined intervention effect. Conclusions Meta-analysis characteristics were strongly associated with the degree of between-study heterogeneity, and predictive distributions for heterogeneity differed substantially across settings. The informative priors provided will be very beneficial in future meta-analyses including few studies. PMID:22461129

Methylenetetrahydrofolate reductase polymorphism C677T is a protective factor for pediatric acute lymphoblastic leukemia in the Chinese population: a meta-analysis.

PubMed

Wang, Haigang; Meng, Lujing; Zhao, Lixia; Wang, Jiali; Liu, Xinchun; Mi, Wenjie

2012-12-01

Two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, were hypothesized to decrease the risk of acute lymphoblastic leukemia (ALL). Studies examining the associations between these two polymorphisms and ALL susceptibility drew inconsistent results. To obtain a reliable conclusion in a Chinese population, we carried out a meta-analysis. In total, 11 studies on C677T polymorphism (1597 cases and 2295 controls) and 10 studies on A1298C polymorphism (1553 cases and 2224 controls) were included in the meta-analysis. We found a significant association between the 677T variant and reduced ALL risk in Chinese children (Dominant model: odds ratio [OR(FE)]=0.73, 95% confidence interval [CI]: 0.63-0.86, p<0.01). Heterogeneity between the studies in the children subgroup was weak and vanished after excluding one study deviating from HWE in the control group (p>0.1). In the adult subgroup, there was no significant association between the C677T variant and ALL risk (Dominant model: OR(RE)=0.88, 95% CI: 0.45-1.72, p=0.72). Significant heterogeneity was found in the adult subgroup in all the genetic model tests (p<0.1). The A1298C polymorphism had an effect on ALL risk neither in adults (Dominant model: OR(FE)=0.95, 95% CI: 0.71-1.27, p=0.72) nor in children (Dominant model: OR(FE)=1.02, 95% CI: 0.87-1.21, p=0.77). No significant heterogeneity between studies on A1298C polymorphism was found in the meta-analysis (p>0.1). The results showed that there was a protective effect of the MTHFR C677T variant on ALL risk in Chinese children.

On meta- and mega-analyses for gene-environment interactions.

PubMed

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M; Whitehead, Alexander S; Blair, Ian A; Vachani, Anil; Clapper, Margie L; Muscat, Joshua E; Lazarus, Philip; Scheet, Paul; Moore, Jason H; Chen, Yong

2017-12-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a "mega" data set, which can be fit by a joint "mega-analysis." Alternatively, analyses can be done at each site, and results across sites can be combined through a "meta-analysis" procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. © 2017 WILEY PERIODICALS, INC.

Introduction to methodology of dose-response meta-analysis for binary outcome: With application on software.

PubMed

Zhang, Chao; Jia, Pengli; Yu, Liu; Xu, Chang

2018-05-01

Dose-response meta-analysis (DRMA) is widely applied to investigate the dose-specific relationship between independent and dependent variables. Such methods have been in use for over 30 years and are increasingly employed in healthcare and clinical decision-making. In this article, we give an overview of the methodology used in DRMA. We summarize the commonly used regression model and the pooled method in DRMA. We also use an example to illustrate how to employ a DRMA by these methods. Five regression models, linear regression, piecewise regression, natural polynomial regression, fractional polynomial regression, and restricted cubic spline regression, were illustrated in this article to fit the dose-response relationship. And two types of pooling approaches, that is, one-stage approach and two-stage approach are illustrated to pool the dose-response relationship across studies. The example showed similar results among these models. Several dose-response meta-analysis methods can be used for investigating the relationship between exposure level and the risk of an outcome. However the methodology of DRMA still needs to be improved. © 2018 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

The Probability Heuristics Model of Syllogistic Reasoning.

ERIC Educational Resources Information Center

Chater, Nick; Oaksford, Mike

1999-01-01

Proposes a probability heuristic model for syllogistic reasoning and confirms the rationality of this heuristic by an analysis of the probabilistic validity of syllogistic reasoning that treats logical inference as a limiting case of probabilistic inference. Meta-analysis and two experiments involving 40 adult participants and using generalized…

Meta-Analyses of Diagnostic Accuracy in Imaging Journals: Analysis of Pooling Techniques and Their Effect on Summary Estimates of Diagnostic Accuracy.

PubMed

McGrath, Trevor A; McInnes, Matthew D F; Korevaar, Daniël A; Bossuyt, Patrick M M

2016-10-01

Purpose To determine whether authors of systematic reviews of diagnostic accuracy studies published in imaging journals used recommended methods for meta-analysis, and to evaluate the effect of traditional methods on summary estimates of sensitivity and specificity. Materials and Methods Medline was searched for published systematic reviews that included meta-analysis of test accuracy data limited to imaging journals published from January 2005 to May 2015. Two reviewers independently extracted study data and classified methods for meta-analysis as traditional (univariate fixed- or random-effects pooling or summary receiver operating characteristic curve) or recommended (bivariate model or hierarchic summary receiver operating characteristic curve). Use of methods was analyzed for variation with time, geographical location, subspecialty, and journal. Results from reviews in which study authors used traditional univariate pooling methods were recalculated with a bivariate model. Results Three hundred reviews met the inclusion criteria, and in 118 (39%) of those, authors used recommended meta-analysis methods. No change in the method used was observed with time (r = 0.54, P = .09); however, there was geographic (χ(2) = 15.7, P = .001), subspecialty (χ(2) = 46.7, P < .001), and journal (χ(2) = 27.6, P < .001) heterogeneity. Fifty-one univariate random-effects meta-analyses were reanalyzed with the bivariate model; the average change in the summary estimate was -1.4% (P < .001) for sensitivity and -2.5% (P < .001) for specificity. The average change in width of the confidence interval was 7.7% (P < .001) for sensitivity and 9.9% (P ≤ .001) for specificity. Conclusion Recommended methods for meta-analysis of diagnostic accuracy in imaging journals are used in a minority of reviews; this has not changed significantly with time. Traditional (univariate) methods allow overestimation of diagnostic accuracy and provide narrower confidence intervals than do recommended (bivariate) methods. (©) RSNA, 2016 Online supplemental material is available for this article.

Bayesian inference on risk differences: an application to multivariate meta-analysis of adverse events in clinical trials.

PubMed

Chen, Yong; Luo, Sheng; Chu, Haitao; Wei, Peng

2013-05-01

Multivariate meta-analysis is useful in combining evidence from independent studies which involve several comparisons among groups based on a single outcome. For binary outcomes, the commonly used statistical models for multivariate meta-analysis are multivariate generalized linear mixed effects models which assume risks, after some transformation, follow a multivariate normal distribution with possible correlations. In this article, we consider an alternative model for multivariate meta-analysis where the risks are modeled by the multivariate beta distribution proposed by Sarmanov (1966). This model have several attractive features compared to the conventional multivariate generalized linear mixed effects models, including simplicity of likelihood function, no need to specify a link function, and has a closed-form expression of distribution functions for study-specific risk differences. We investigate the finite sample performance of this model by simulation studies and illustrate its use with an application to multivariate meta-analysis of adverse events of tricyclic antidepressants treatment in clinical trials.

Spatial Bayesian latent factor regression modeling of coordinate-based meta-analysis data.

PubMed

Montagna, Silvia; Wager, Tor; Barrett, Lisa Feldman; Johnson, Timothy D; Nichols, Thomas E

2018-03-01

Now over 20 years old, functional MRI (fMRI) has a large and growing literature that is best synthesised with meta-analytic tools. As most authors do not share image data, only the peak activation coordinates (foci) reported in the article are available for Coordinate-Based Meta-Analysis (CBMA). Neuroimaging meta-analysis is used to (i) identify areas of consistent activation; and (ii) build a predictive model of task type or cognitive process for new studies (reverse inference). To simultaneously address these aims, we propose a Bayesian point process hierarchical model for CBMA. We model the foci from each study as a doubly stochastic Poisson process, where the study-specific log intensity function is characterized as a linear combination of a high-dimensional basis set. A sparse representation of the intensities is guaranteed through latent factor modeling of the basis coefficients. Within our framework, it is also possible to account for the effect of study-level covariates (meta-regression), significantly expanding the capabilities of the current neuroimaging meta-analysis methods available. We apply our methodology to synthetic data and neuroimaging meta-analysis datasets. © 2017, The International Biometric Society.

Univariate and bivariate likelihood-based meta-analysis methods performed comparably when marginal sensitivity and specificity were the targets of inference.

PubMed

Dahabreh, Issa J; Trikalinos, Thomas A; Lau, Joseph; Schmid, Christopher H

2017-03-01

To compare statistical methods for meta-analysis of sensitivity and specificity of medical tests (e.g., diagnostic or screening tests). We constructed a database of PubMed-indexed meta-analyses of test performance from which 2 × 2 tables for each included study could be extracted. We reanalyzed the data using univariate and bivariate random effects models fit with inverse variance and maximum likelihood methods. Analyses were performed using both normal and binomial likelihoods to describe within-study variability. The bivariate model using the binomial likelihood was also fit using a fully Bayesian approach. We use two worked examples-thoracic computerized tomography to detect aortic injury and rapid prescreening of Papanicolaou smears to detect cytological abnormalities-to highlight that different meta-analysis approaches can produce different results. We also present results from reanalysis of 308 meta-analyses of sensitivity and specificity. Models using the normal approximation produced sensitivity and specificity estimates closer to 50% and smaller standard errors compared to models using the binomial likelihood; absolute differences of 5% or greater were observed in 12% and 5% of meta-analyses for sensitivity and specificity, respectively. Results from univariate and bivariate random effects models were similar, regardless of estimation method. Maximum likelihood and Bayesian methods produced almost identical summary estimates under the bivariate model; however, Bayesian analyses indicated greater uncertainty around those estimates. Bivariate models produced imprecise estimates of the between-study correlation of sensitivity and specificity. Differences between methods were larger with increasing proportion of studies that were small or required a continuity correction. The binomial likelihood should be used to model within-study variability. Univariate and bivariate models give similar estimates of the marginal distributions for sensitivity and specificity. Bayesian methods fully quantify uncertainty and their ability to incorporate external evidence may be useful for imprecisely estimated parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials

PubMed Central

GRIFFITHS, U. K.; CLARK, A.; GESSNER, B.; MINERS, A.; SANDERSON, C.; SEDYANINGSIH, E. R.; MULHOLLAND, K. E.

2012-01-01

SUMMARY Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine. PMID:22583474

Multivariate meta-analysis: a robust approach based on the theory of U-statistic.

PubMed

Ma, Yan; Mazumdar, Madhu

2011-10-30

Meta-analysis is the methodology for combining findings from similar research studies asking the same question. When the question of interest involves multiple outcomes, multivariate meta-analysis is used to synthesize the outcomes simultaneously taking into account the correlation between the outcomes. Likelihood-based approaches, in particular restricted maximum likelihood (REML) method, are commonly utilized in this context. REML assumes a multivariate normal distribution for the random-effects model. This assumption is difficult to verify, especially for meta-analysis with small number of component studies. The use of REML also requires iterative estimation between parameters, needing moderately high computation time, especially when the dimension of outcomes is large. A multivariate method of moments (MMM) is available and is shown to perform equally well to REML. However, there is a lack of information on the performance of these two methods when the true data distribution is far from normality. In this paper, we propose a new nonparametric and non-iterative method for multivariate meta-analysis on the basis of the theory of U-statistic and compare the properties of these three procedures under both normal and skewed data through simulation studies. It is shown that the effect on estimates from REML because of non-normal data distribution is marginal and that the estimates from MMM and U-statistic-based approaches are very similar. Therefore, we conclude that for performing multivariate meta-analysis, the U-statistic estimation procedure is a viable alternative to REML and MMM. Easy implementation of all three methods are illustrated by their application to data from two published meta-analysis from the fields of hip fracture and periodontal disease. We discuss ideas for future research based on U-statistic for testing significance of between-study heterogeneity and for extending the work to meta-regression setting. Copyright © 2011 John Wiley & Sons, Ltd.

Methods for network meta-analysis of continuous outcomes using individual patient data: a case study in acupuncture for chronic pain.

PubMed

Saramago, Pedro; Woods, Beth; Weatherly, Helen; Manca, Andrea; Sculpher, Mark; Khan, Kamran; Vickers, Andrew J; MacPherson, Hugh

2016-10-06

Network meta-analysis methods, which are an extension of the standard pair-wise synthesis framework, allow for the simultaneous comparison of multiple interventions and consideration of the entire body of evidence in a single statistical model. There are well-established advantages to using individual patient data to perform network meta-analysis and methods for network meta-analysis of individual patient data have already been developed for dichotomous and time-to-event data. This paper describes appropriate methods for the network meta-analysis of individual patient data on continuous outcomes. This paper introduces and describes network meta-analysis of individual patient data models for continuous outcomes using the analysis of covariance framework. Comparisons are made between this approach and change score and final score only approaches, which are frequently used and have been proposed in the methodological literature. A motivating example on the effectiveness of acupuncture for chronic pain is used to demonstrate the methods. Individual patient data on 28 randomised controlled trials were synthesised. Consistency of endpoints across the evidence base was obtained through standardisation and mapping exercises. Individual patient data availability avoided the use of non-baseline-adjusted models, allowing instead for analysis of covariance models to be applied and thus improving the precision of treatment effect estimates while adjusting for baseline imbalance. The network meta-analysis of individual patient data using the analysis of covariance approach is advocated to be the most appropriate modelling approach for network meta-analysis of continuous outcomes, particularly in the presence of baseline imbalance. Further methods developments are required to address the challenge of analysing aggregate level data in the presence of baseline imbalance.

On meta- and mega-analyses for gene–environment interactions

PubMed Central

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M.; Whitehead, Alexander S.; Blair, Ian A.; Vachani, Anil; Clapper, Margie L.; Muscat, Joshua E.; Lazarus, Philip; Scheet, Paul; Moore, Jason H.; Chen, Yong

2017-01-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a “mega” data set, which can be fit by a joint “mega-analysis.” Alternatively, analyses can be done at each site, and results across sites can be combined through a “meta-analysis” procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. PMID:29110346

Mixture models in diagnostic meta-analyses--clustering summary receiver operating characteristic curves accounted for heterogeneity and correlation.

PubMed

Schlattmann, Peter; Verba, Maryna; Dewey, Marc; Walther, Mario

2015-01-01

Bivariate linear and generalized linear random effects are frequently used to perform a diagnostic meta-analysis. The objective of this article was to apply a finite mixture model of bivariate normal distributions that can be used for the construction of componentwise summary receiver operating characteristic (sROC) curves. Bivariate linear random effects and a bivariate finite mixture model are used. The latter model is developed as an extension of a univariate finite mixture model. Two examples, computed tomography (CT) angiography for ruling out coronary artery disease and procalcitonin as a diagnostic marker for sepsis, are used to estimate mean sensitivity and mean specificity and to construct sROC curves. The suggested approach of a bivariate finite mixture model identifies two latent classes of diagnostic accuracy for the CT angiography example. Both classes show high sensitivity but mainly two different levels of specificity. For the procalcitonin example, this approach identifies three latent classes of diagnostic accuracy. Here, sensitivities and specificities are quite different as such that sensitivity increases with decreasing specificity. Additionally, the model is used to construct componentwise sROC curves and to classify individual studies. The proposed method offers an alternative approach to model between-study heterogeneity in a diagnostic meta-analysis. Furthermore, it is possible to construct sROC curves even if a positive correlation between sensitivity and specificity is present. Copyright © 2015 Elsevier Inc. All rights reserved.

Meta-analysis of diagnostic tests accounting for disease prevalence: a new model using trivariate copulas.

PubMed

Hoyer, A; Kuss, O

2015-05-20

In real life and somewhat contrary to biostatistical textbook knowledge, sensitivity and specificity (and not only predictive values) of diagnostic tests can vary with the underlying prevalence of disease. In meta-analysis of diagnostic studies, accounting for this fact naturally leads to a trivariate expansion of the traditional bivariate logistic regression model with random study effects. In this paper, a new model is proposed using trivariate copulas and beta-binomial marginal distributions for sensitivity, specificity, and prevalence as an expansion of the bivariate model. Two different copulas are used, the trivariate Gaussian copula and a trivariate vine copula based on the bivariate Plackett copula. This model has a closed-form likelihood, so standard software (e.g., SAS PROC NLMIXED) can be used. The results of a simulation study have shown that the copula models perform at least as good but frequently better than the standard model. The methods are illustrated by two examples. Copyright © 2015 John Wiley & Sons, Ltd.

Metacognition and evidence analysis instruction: an educational framework and practical experience.

PubMed

Parrott, J Scott; Rubinstein, Matthew L

2015-08-21

The role of metacognitive skills in the evidence analysis process has received little attention in the research literature. While the steps of the evidence analysis process are well defined, the role of higher-level cognitive operations (metacognitive strategies) in integrating the steps of the process is not well understood. In part, this is because it is not clear where and how metacognition is implicated in the evidence analysis process nor how these skills might be taught. The purposes of this paper are to (a) suggest a model for identifying critical thinking and metacognitive skills in evidence analysis instruction grounded in current educational theory and research and (b) demonstrate how freely available systematic review/meta-analysis tools can be used to focus on higher-order metacognitive skills, while providing a framework for addressing common student weaknesses. The final goal of this paper is to provide an instructional framework that can generate critique and elaboration while providing the conceptual basis and rationale for future research agendas on this topic.

An epigenome-wide association meta-analysis of prenatal maternal stress in neonates: A model approach for replication

PubMed Central

Rijlaarsdam, Jolien; Pappa, Irene; Walton, Esther; Bakermans-Kranenburg, Marian J.; Mileva-Seitz, Viara R.; Rippe, Ralph C.A.; Roza, Sabine J.; Jaddoe, Vincent W.V.; Verhulst, Frank C.; Felix, Janine F.; Cecil, Charlotte A.M.; Relton, Caroline L.; Gaunt, Tom R.; McArdle, Wendy; Mill, Jonathan; Barker, Edward D.; Tiemeier, Henning; van IJzendoorn, Marinus H.

2016-01-01

ABSTRACT Prenatal maternal stress exposure has been associated with neonatal differential DNA methylation. However, the available evidence in humans is largely based on candidate gene methylation studies, where only a few CpG sites were evaluated. The aim of this study was to examine the association between prenatal exposure to maternal stress and offspring genome-wide cord blood methylation using different methods. First, we conducted a meta-analysis and follow-up pathway analyses. Second, we used novel region discovery methods [i.e., differentially methylated regions (DMRs) analyses]. To this end, we used data from two independent population-based studies, the Generation R Study (n = 912) and the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 828), to (i) measure genome-wide DNA methylation in cord blood and (ii) extract a prenatal maternal stress composite. The meta-analysis (ntotal = 1,740) revealed no epigenome-wide (meta P <1.00e-07) associations of prenatal maternal stress exposure with neonatal differential DNA methylation. Follow-up analyses of the top hits derived from our epigenome-wide meta-analysis (meta P <1.00e-04) indicated an over-representation of the methyltransferase activity pathway. We identified no Bonferroni-corrected (P <1.00e-06) DMRs associated with prenatal maternal stress exposure. Combining data from two independent population-based samples in an epigenome-wide meta-analysis, the current study indicates that there are no large effects of prenatal maternal stress exposure on neonatal DNA methylation. Such replication efforts are essential in the search for robust associations, whether derived from candidate gene methylation or epigenome-wide studies. PMID:26889969

MetaComp: comprehensive analysis software for comparative meta-omics including comparative metagenomics.

PubMed

Zhai, Peng; Yang, Longshu; Guo, Xiao; Wang, Zhe; Guo, Jiangtao; Wang, Xiaoqi; Zhu, Huaiqiu

2017-10-02

During the past decade, the development of high throughput nucleic sequencing and mass spectrometry analysis techniques have enabled the characterization of microbial communities through metagenomics, metatranscriptomics, metaproteomics and metabolomics data. To reveal the diversity of microbial communities and interactions between living conditions and microbes, it is necessary to introduce comparative analysis based upon integration of all four types of data mentioned above. Comparative meta-omics, especially comparative metageomics, has been established as a routine process to highlight the significant differences in taxon composition and functional gene abundance among microbiota samples. Meanwhile, biologists are increasingly concerning about the correlations between meta-omics features and environmental factors, which may further decipher the adaptation strategy of a microbial community. We developed a graphical comprehensive analysis software named MetaComp comprising a series of statistical analysis approaches with visualized results for metagenomics and other meta-omics data comparison. This software is capable to read files generated by a variety of upstream programs. After data loading, analyses such as multivariate statistics, hypothesis testing of two-sample, multi-sample as well as two-group sample and a novel function-regression analysis of environmental factors are offered. Here, regression analysis regards meta-omic features as independent variable and environmental factors as dependent variables. Moreover, MetaComp is capable to automatically choose an appropriate two-group sample test based upon the traits of input abundance profiles. We further evaluate the performance of its choice, and exhibit applications for metagenomics, metaproteomics and metabolomics samples. MetaComp, an integrative software capable for applying to all meta-omics data, originally distills the influence of living environment on microbial community by regression analysis. Moreover, since the automatically chosen two-group sample test is verified to be outperformed, MetaComp is friendly to users without adequate statistical training. These improvements are aiming to overcome the new challenges under big data era for all meta-omics data. MetaComp is available at: http://cqb.pku.edu.cn/ZhuLab/MetaComp/ and https://github.com/pzhaipku/MetaComp/ .

Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis.

PubMed

Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2016-05-01

Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003). This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Meta-analysis in Stata using gllamm.

PubMed

Bagos, Pantelis G

2015-12-01

There are several user-written programs for performing meta-analysis in Stata (Stata Statistical Software: College Station, TX: Stata Corp LP). These include metan, metareg, mvmeta, and glst. However, there are several cases for which these programs do not suffice. For instance, there is no software for performing univariate meta-analysis with correlated estimates, for multilevel or hierarchical meta-analysis, or for meta-analysis of longitudinal data. In this work, we show with practical applications that many disparate models, including but not limited to the ones mentioned earlier, can be fitted using gllamm. The software is very versatile and can handle a wide variety of models with applications in a wide range of disciplines. The method presented here takes advantage of these modeling capabilities and makes use of appropriate transformations, based on the Cholesky decomposition of the inverse of the covariance matrix, known as generalized least squares, in order to handle correlated data. The models described earlier can be thought of as special instances of a general linear mixed-model formulation, but to the author's knowledge, a general exposition in order to incorporate all the available models for meta-analysis as special cases and the instructions to fit them in Stata has not been presented so far. Source code is available at http:www.compgen.org/tools/gllamm. Copyright © 2015 John Wiley & Sons, Ltd.

A Review of Meta-Analysis Packages in R

ERIC Educational Resources Information Center

Polanin, Joshua R.; Hennessy, Emily A.; Tanner-Smith, Emily E.

2017-01-01

Meta-analysis is a statistical technique that allows an analyst to synthesize effect sizes from multiple primary studies. To estimate meta-analysis models, the open-source statistical environment R is quickly becoming a popular choice. The meta-analytic community has contributed to this growth by developing numerous packages specific to…

Methods for the Joint Meta-Analysis of Multiple Tests

ERIC Educational Resources Information Center

Trikalinos, Thomas A.; Hoaglin, David C.; Small, Kevin M.; Terrin, Norma; Schmid, Christopher H.

2014-01-01

Existing methods for meta-analysis of diagnostic test accuracy focus primarily on a single index test. We propose models for the joint meta-analysis of studies comparing multiple index tests on the same participants in paired designs. These models respect the grouping of data by studies, account for the within-study correlation between the tests'…

Illustration of a Multilevel Model for Meta-Analysis

ERIC Educational Resources Information Center

de la Torre, Jimmy; Camilli, Gregory; Vargas, Sadako; Vernon, R. Fox

2007-01-01

In this article, the authors present a multilevel (or hierarchical linear) model that illustrates issues in the application of the model to data from meta-analytic studies. In doing so, several issues are discussed that typically arise in the course of a meta-analysis. These include the presence of non-zero between-study variability, how multiple…

How to Make Nothing Out of Something: Analyses of the Impact of Study Sampling and Statistical Interpretation in Misleading Meta-Analytic Conclusions

PubMed Central

Cunningham, Michael R.; Baumeister, Roy F.

2016-01-01

The limited resource model states that self-control is governed by a relatively finite set of inner resources on which people draw when exerting willpower. Once self-control resources have been used up or depleted, they are less available for other self-control tasks, leading to a decrement in subsequent self-control success. The depletion effect has been studied for over 20 years, tested or extended in more than 600 studies, and supported in an independent meta-analysis (Hagger et al., 2010). Meta-analyses are supposed to reduce bias in literature reviews. Carter et al.’s (2015) meta-analysis, by contrast, included a series of questionable decisions involving sampling, methods, and data analysis. We provide quantitative analyses of key sampling issues: exclusion of many of the best depletion studies based on idiosyncratic criteria and the emphasis on mini meta-analyses with low statistical power as opposed to the overall depletion effect. We discuss two key methodological issues: failure to code for research quality, and the quantitative impact of weak studies by novice researchers. We discuss two key data analysis issues: questionable interpretation of the results of trim and fill and Funnel Plot Asymmetry test procedures, and the use and misinterpretation of the untested Precision Effect Test and Precision Effect Estimate with Standard Error (PEESE) procedures. Despite these serious problems, the Carter et al. (2015) meta-analysis results actually indicate that there is a real depletion effect – contrary to their title. PMID:27826272

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

PubMed Central

Scherag, André; Dina, Christian; Hinney, Anke; Vatin, Vincent; Scherag, Susann; Vogel, Carla I. G.; Müller, Timo D.; Grallert, Harald; Wichmann, H.-Erich; Balkau, Beverley; Heude, Barbara; Jarvelin, Marjo-Riitta; Hartikainen, Anna-Liisa; Levy-Marchal, Claire; Weill, Jacques; Delplanque, Jérôme; Körner, Antje; Kiess, Wieland; Kovacs, Peter; Rayner, Nigel W.; Prokopenko, Inga; McCarthy, Mark I.; Schäfer, Helmut; Jarick, Ivonne; Boeing, Heiner; Fisher, Eva; Reinehr, Thomas; Heinrich, Joachim; Rzehak, Peter; Berdel, Dietrich; Borte, Michael; Biebermann, Heike; Krude, Heiko; Rosskopf, Dieter; Rimmbach, Christian; Rief, Winfried; Fromme, Tobias; Klingenspor, Martin; Schürmann, Annette; Schulz, Nadja; Nöthen, Markus M.; Mühleisen, Thomas W.; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Boes, Tanja; Illig, Thomas; Froguel, Philippe; Hebebrand, Johannes; Meyre, David

2010-01-01

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85×10−8 in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84×10−7), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at ∼1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults. PMID:20421936

Don’t Like RDF Reification? Making Statements about Statements Using Singleton Property

PubMed Central

Nguyen, Vinh; Bodenreider, Olivier; Sheth, Amit

2015-01-01

Statements about RDF statements, or meta triples, provide additional information about individual triples, such as the source, the occurring time or place, or the certainty. Integrating such meta triples into semantic knowledge bases would enable the querying and reasoning mechanisms to be aware of provenance, time, location, or certainty of triples. However, an efficient RDF representation for such meta knowledge of triples remains challenging. The existing standard reification approach allows such meta knowledge of RDF triples to be expressed using RDF by two steps. The first step is representing the triple by a Statement instance which has subject, predicate, and object indicated separately in three different triples. The second step is creating assertions about that instance as if it is a statement. While reification is simple and intuitive, this approach does not have formal semantics and is not commonly used in practice as described in the RDF Primer. In this paper, we propose a novel approach called Singleton Property for representing statements about statements and provide a formal semantics for it. We explain how this singleton property approach fits well with the existing syntax and formal semantics of RDF, and the syntax of SPARQL query language. We also demonstrate the use of singleton property in the representation and querying of meta knowledge in two examples of Semantic Web knowledge bases: YAGO2 and BKR. Our experiments on the BKR show that the singleton property approach gives a decent performance in terms of number of triples, query length and query execution time compared to existing approaches. This approach, which is also simple and intuitive, can be easily adopted for representing and querying statements about statements in other knowledge bases. PMID:25750938

In Sync and in Control: A Meta-Analysis of Parent-Child Positive Behavioral Synchrony and Youth Self-Regulation.

PubMed

Davis, Molly; Bilms, Joanie; Suveg, Cynthia

2017-12-01

A growing body of research has highlighted the connection between parent-child positive behavioral synchrony and youth self-regulation; however, this association has yet to be the focus of a meta-analytic review. Therefore, the present meta-analysis aimed to estimate the magnitude of the relation between parent-child positive behavioral synchrony and youth self-regulation and to identify moderator variables that can explain the variability in the degree of this association across the extant literature. A thorough literature search of two major databases, in addition to scanning the reference sections of relevant articles, yielded a total of 10 peer-reviewed articles (24 effect sizes, 658 children) that were eligible for inclusion in the current meta-analysis. Results from the overall mean effect size calculation using a random-effects model indicated that parent-child positive behavioral synchrony was significantly, positively correlated with youth self-regulation and the effect size was medium. Children's ages at the time of synchrony and self-regulation measurements, as well as parent gender, served as significant moderator variables. Findings from the present meta-analysis can help to refine existing theoretical models on the role of the parent-child relationship in youth adjustment. Prevention and intervention efforts may benefit from an increased emphasis on building parent-child positive behavioral synchrony to promote youth self-regulation and thus children's overall well-being. © 2016 Family Process Institute.

Spreadsheet analysis of stability and meta-stability of low-dimensional magnetic particles using the Ising approach

NASA Astrophysics Data System (ADS)

Ehrmann, Andrea; Blachowicz, Tomasz; Zghidi, Hafed

2015-05-01

Modelling hysteresis behaviour, as it can be found in a broad variety of dynamical systems, can be performed in different ways. An elementary approach, applied for a set of elementary cells, which uses only two possible states per cell, is the Ising model. While such Ising models allow for a simulation of many systems with sufficient accuracy, they nevertheless depict some typical features which must be taken into account with proper care, such as meta-stability or the externally applied field sweeping speed. This paper gives a general overview of recent results from Ising models from the perspective of a didactic model, based on a 2D spreadsheet analysis, which can be used also for solving general scientific problems where direct next-neighbour interactions take place.

Preparing the Dutch delta for future droughts: model based support in the national Delta Programme

NASA Astrophysics Data System (ADS)

ter Maat, Judith; Haasnoot, Marjolijn; van der Vat, Marnix; Hunink, Joachim; Prinsen, Geert; Visser, Martijn

2014-05-01

Keywords: uncertainty, policymaking, adaptive policies, fresh water management, droughts, Netherlands, Dutch Deltaprogramme, physically-based complex model, theory-motivated meta-model To prepare the Dutch Delta for future droughts and water scarcity, a nation-wide 4-year project, called Delta Programme, is established to assess impacts of climate scenarios and socio-economic developments and to explore policy options. The results should contribute to a national adaptive plan that is able to adapt to future uncertain conditions, if necessary. For this purpose, we followed a model-based step-wise approach, wherein both physically-based complex models and theory-motivated meta-models were used. First step (2010-2011) was to make a quantitative problem description. This involved a sensitivity analysis of the water system for drought situations under current and future conditions. The comprehensive Dutch national hydrological instrument was used for this purpose and further developed. Secondly (2011-2012) our main focus was on making an inventory of potential actions together with stakeholders. We assessed efficacy, sell-by date of actions, and reassessed vulnerabilities and opportunities for the future water supply system if actions were (not) taken. A rapid assessment meta-model was made based on the complex model. The effects of all potential measures were included in the tool. Thirdly (2012-2013), with support of the rapid assessment model, we assessed the efficacy of policy actions over time for an ensemble of possible futures including sea level rise and climate and land use change. Last step (2013-2014) involves the selection of preferred actions from a set of promising actions that meet the defined objectives. These actions are all modeled and evaluated using the complex model. The outcome of the process will be an adaptive management plan. The adaptive plan describes a set of preferred policy pathways - sequences of policy actions - to achieve targets under changing conditions. The plan commits to short term actions, and identifies signpost indicators and trigger values to assess if next actions of the identified policy pathways need to be implemented or if reassessment of the plan is needed. For example, river discharges could be measured to monitor changes in low discharges as a result of climate change, and assess whether policy options such as diverting more water the main fresh water lake (IJsselmeer) need to be implemented sooner or later or not at all. The adaptive plan of the Delta Programme will be presented in 2014. First lessons of this part of the Delta Programme can already be drawn: Both the complex and meta-model had its own purpose in each phase. The meta-model was particularly useful for identifying promising policy options and for consultation of stakeholders due to the instant response. The complex model had much more opportunities to assess impacts of regional policy actions, and was supported by regional stakeholders that recognized their areas better in this model. Different sector impact assessment modules are also included in the workflow of the complex model. However, the complex model has a long runtime (i.e. three days for 1 year simulation or more than 100 days for 35 year time series simulation), which makes it less suitable to support the dynamic policy process on instant demand and interactively.

Evaluating the Quality of Evidence from a Network Meta-Analysis

PubMed Central

Salanti, Georgia; Del Giovane, Cinzia; Chaimani, Anna; Caldwell, Deborah M.; Higgins, Julian P. T.

2014-01-01

Systematic reviews that collate data about the relative effects of multiple interventions via network meta-analysis are highly informative for decision-making purposes. A network meta-analysis provides two types of findings for a specific outcome: the relative treatment effect for all pairwise comparisons, and a ranking of the treatments. It is important to consider the confidence with which these two types of results can enable clinicians, policy makers and patients to make informed decisions. We propose an approach to determining confidence in the output of a network meta-analysis. Our proposed approach is based on methodology developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group for pairwise meta-analyses. The suggested framework for evaluating a network meta-analysis acknowledges (i) the key role of indirect comparisons (ii) the contributions of each piece of direct evidence to the network meta-analysis estimates of effect size; (iii) the importance of the transitivity assumption to the validity of network meta-analysis; and (iv) the possibility of disagreement between direct evidence and indirect evidence. We apply our proposed strategy to a systematic review comparing topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations. The proposed framework can be used to determine confidence in the results from a network meta-analysis. Judgements about evidence from a network meta-analysis can be different from those made about evidence from pairwise meta-analyses. PMID:24992266

The effectiveness and safety of aminocaproic acid for reducing blood loss in total knee and hip arthroplasty: A meta-analysis.

PubMed

Dong, Qiang; Zhang, Yinguang; Sun, Xiang; Hu, Fangke

2018-04-01

This meta-analysis aimed to evaluate the safety and efficacy of aminocaproic acid in total knee arthroplasty (TKA) and total hip arthroplasty (THA). The electronic databases include PubMed, Medline, Embase, Web of Science and the Cochrane Library from inception to January, 2018. Two reviewers abstracted total blood loss, hemoglobin drop, transfusion requirements, and postoperative complications. Data were using fixed-effects or random-effects models with weighted mean differences and risk difference for continuous and dichotomous variables, respectively. STATA 14.0 was used to perform the meta-analysis. Six studies encompassing 756 participants were retrieved for this meta-analysis. Our study indicated that intravenous aminocaproic acid was associated with a significantly reduction in total blood loss, hemoglobin drop and need for transfusion. Additionally, no increased risk of thromboembolic events were identified. Based on the present meta-analysis, intravenous aminocaproic acid is effective and safe in total knee and hip arthroplasty without increasing the incidence of thromboembolic events. Further studies should focus on the comparison of aminocaproic acid and TXA in arthroplasties. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

What proportion of people with hip and knee osteoarthritis meet physical activity guidelines? A systematic review and meta-analysis.

PubMed

Wallis, J A; Webster, K E; Levinger, P; Taylor, N F

2013-11-01

To determine the proportion of people with hip and knee osteoarthritis that meet physical activity guidelines recommended for adults and older adults. Systematic review with meta-analysis of studies measuring physical activity of participants with hip and knee osteoarthritis using an activity monitor. Physical activity levels were calculated using the mean average [95% confidence interval (CI)] weighted according to sample size. Meta-analyses determined the proportion of people meeting physical activity guidelines and recommendations of (1) ≥150 min per week of moderate to vigorous physical activity (MVPA) in bouts of ≥10 min; (2) ≥150 min per week of MVPA in absence of bouts; (3) ≥10,000 steps per day and ≥7000 steps per day. The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of the evidence. For knee osteoarthritis, 21 studies involving 3266 participants averaged 50 min per week (95% CI = 46, 55) of MVPA when measured in bouts of ≥10 min, 131 min per week (95% CI = 125, 137) of MVPA, and 7753 daily steps (95% CI = 7582, 7924). Proportion meta-analyses provided high quality evidence that 13% (95% CI = 7, 20) completed ≥150 min per week of MVPA in bouts of ≥10 min, low quality evidence that 41% (95% CI = 23, 61) completed ≥150 min per week of MVPA in absence of bouts, moderate quality evidence that 19% (95% CI = 8, 33) completed ≥10,000 steps per day, and low quality evidence that 48% (95% CI = 31, 65) completed ≥7000 steps per day. For hip osteoarthritis, 11 studies involving 325 participants averaged 160 min per week (95% CI = 114, 216) of MVPA when measured in bouts of ≥10 min, 189 min per week (95% CI = 166, 212) of MVPA, and 8174 daily steps (95% CI = 7670, 8678). Proportion meta-analyses provided low quality evidence that 58% (95% CI = 18, 92) completed ≥150 min per week of MVPA in absence of bouts, low quality evidence that 30% (95% CI = 13, 50) completed ≥10,000 steps per day, and low quality evidence that 60% (95% CI = 47, 73) completed ≥7000 steps per day. A small to moderate proportion of people with knee and hip osteoarthritis met physical activity guidelines and recommended daily steps. Future research should establish the effects of increasing physical activity in this population to meet the current physical activity guidelines. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The Economic Impacts of Climate Change on Agriculture: New Damage Functions from a Meta-Analsis and the GGCMI

NASA Astrophysics Data System (ADS)

Moore, F. C.; Baldos, U. L. C.; Hertel, T. W.; Diaz, D.

2016-12-01

Substantial advances have been made in recent years in understanding the effects of climate change on agriculture, but this is not currently represented in economic models used to quantify the benefits of reducing greenhouse gas emissions. In fact, the science regarding climate change impacts on agriculture in these models dates to the early 1990s or before. In this paper we derive new economic damage functions for the agricultural sector based on two methods for aggregating current scientific understanding of the impacts of warming on yields. We first present a new meta-analysis based on a review of the agronomic literature performed for the IPCC 5th Assessment Report and compare results from this approach with findings from the AgMIP Global Gridded Crop Model Intercomparison (GGCMI). We find yield impacts implied by the meta-analysis are generally more negative than those from the GGCMI, particularly at higher latitudes, but show substantial agreement in many areas. We then use both yield products as input to the Global Trade Analysis Project (GTAP) computable general equilibrium (CGE) model in order to estimate the welfare consequences of these yield shocks and to produce two new economic damage functions. These damage functions are consistently more negative than the current representation of agricultural damages in Integrated Asessment Models (IAMs), in some cases substantially so. Replacing the existing damage functions with those based on more recent science increases the social cost of carbon (SCC) by between 43% (GGCMI) and 143% (Meta-Analysis). In addition to presenting a new mutli-crop, multi-model gridded yield impact prouct that complements the GGCMI, this is also the first end-to-end study that directly links the biophysical impacts of climate change to the SCC, something we believe essential to improving the integrity of IAMs going forward.

The Influence of Study-Level Inference Models and Study Set Size on Coordinate-Based fMRI Meta-Analyses

PubMed Central

Bossier, Han; Seurinck, Ruth; Kühn, Simone; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Martinot, Jean-Luc; Lemaitre, Herve; Paus, Tomáš; Millenet, Sabina; Moerkerke, Beatrijs

2018-01-01

Given the increasing amount of neuroimaging studies, there is a growing need to summarize published results. Coordinate-based meta-analyses use the locations of statistically significant local maxima with possibly the associated effect sizes to aggregate studies. In this paper, we investigate the influence of key characteristics of a coordinate-based meta-analysis on (1) the balance between false and true positives and (2) the activation reliability of the outcome from a coordinate-based meta-analysis. More particularly, we consider the influence of the chosen group level model at the study level [fixed effects, ordinary least squares (OLS), or mixed effects models], the type of coordinate-based meta-analysis [Activation Likelihood Estimation (ALE) that only uses peak locations, fixed effects, and random effects meta-analysis that take into account both peak location and height] and the amount of studies included in the analysis (from 10 to 35). To do this, we apply a resampling scheme on a large dataset (N = 1,400) to create a test condition and compare this with an independent evaluation condition. The test condition corresponds to subsampling participants into studies and combine these using meta-analyses. The evaluation condition corresponds to a high-powered group analysis. We observe the best performance when using mixed effects models in individual studies combined with a random effects meta-analysis. Moreover the performance increases with the number of studies included in the meta-analysis. When peak height is not taken into consideration, we show that the popular ALE procedure is a good alternative in terms of the balance between type I and II errors. However, it requires more studies compared to other procedures in terms of activation reliability. Finally, we discuss the differences, interpretations, and limitations of our results. PMID:29403344

Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data.

PubMed

Jolliffe, David A; Greenberg, Lauren; Hooper, Richard L; Griffiths, Christopher J; Camargo, Carlos A; Kerley, Conor P; Jensen, Megan E; Mauger, David; Stelmach, Iwona; Urashima, Mitsuyoshi; Martineau, Adrian R

2017-11-01

A previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown. For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D 3 or vitamin D 2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953. Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56-0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11-0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58-1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; p interaction =0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I 2 =0·0, p=0·56). Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients. Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25). Copyright © 2017 Elsevier Ltd. All rights reserved.

A Multivariate Model for the Meta-Analysis of Study Level Survival Data at Multiple Times

ERIC Educational Resources Information Center

Jackson, Dan; Rollins, Katie; Coughlin, Patrick

2014-01-01

Motivated by our meta-analytic dataset involving survival rates after treatment for critical leg ischemia, we develop and apply a new multivariate model for the meta-analysis of study level survival data at multiple times. Our data set involves 50 studies that provide mortality rates at up to seven time points, which we model simultaneously, and…

Enhanced semantic interoperability by profiling health informatics standards.

PubMed

López, Diego M; Blobel, Bernd

2009-01-01

Several standards applied to the healthcare domain support semantic interoperability. These standards are far from being completely adopted in health information system development, however. The objective of this paper is to provide a method and suggest the necessary tooling for reusing standard health information models, by that way supporting the development of semantically interoperable systems and components. The approach is based on the definition of UML Profiles. UML profiling is a formal modeling mechanism to specialize reference meta-models in such a way that it is possible to adapt those meta-models to specific platforms or domains. A health information model can be considered as such a meta-model. The first step of the introduced method identifies the standard health information models and tasks in the software development process in which healthcare information models can be reused. Then, the selected information model is formalized as a UML Profile. That Profile is finally applied to system models, annotating them with the semantics of the information model. The approach is supported on Eclipse-based UML modeling tools. The method is integrated into a comprehensive framework for health information systems development, and the feasibility of the approach is demonstrated in the analysis, design, and implementation of a public health surveillance system, reusing HL7 RIM and DIMs specifications. The paper describes a method and the necessary tooling for reusing standard healthcare information models. UML offers several advantages such as tooling support, graphical notation, exchangeability, extensibility, semi-automatic code generation, etc. The approach presented is also applicable for harmonizing different standard specifications.

Testing moderation in network meta-analysis with individual participant data

PubMed Central

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George; Kellam, Sheppard G.; Liu, Lei

2016-01-01

Summary Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data (IPD) may increase the sensitivity of NMA for detecting moderator effects, as compared to aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new network meta-analysis diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within- and between-trial heterogeneity, and can include participant-level covariates. Within this framework we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to IPD as compared to study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. PMID:26841367

Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis.

PubMed

Suurmond, Robert; van Rhee, Henk; Hak, Tony

2017-12-01

We present a new tool for meta-analysis, Meta-Essentials, which is free of charge and easy to use. In this paper, we introduce the tool and compare its features to other tools for meta-analysis. We also provide detailed information on the validation of the tool. Although free of charge and simple, Meta-Essentials automatically calculates effect sizes from a wide range of statistics and can be used for a wide range of meta-analysis applications, including subgroup analysis, moderator analysis, and publication bias analyses. The confidence interval of the overall effect is automatically based on the Knapp-Hartung adjustment of the DerSimonian-Laird estimator. However, more advanced meta-analysis methods such as meta-analytical structural equation modelling and meta-regression with multiple covariates are not available. In summary, Meta-Essentials may prove a valuable resource for meta-analysts, including researchers, teachers, and students. © 2017 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis.

PubMed

Mocellin, Simone; Verdi, Daunia; Nitti, Donato

2009-10-01

Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03-1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.

Bivariate random-effects meta-analysis models for diagnostic test accuracy studies using arcsine-based transformations.

PubMed

Negeri, Zelalem F; Shaikh, Mateen; Beyene, Joseph

2018-05-11

Diagnostic or screening tests are widely used in medical fields to classify patients according to their disease status. Several statistical models for meta-analysis of diagnostic test accuracy studies have been developed to synthesize test sensitivity and specificity of a diagnostic test of interest. Because of the correlation between test sensitivity and specificity, modeling the two measures using a bivariate model is recommended. In this paper, we extend the current standard bivariate linear mixed model (LMM) by proposing two variance-stabilizing transformations: the arcsine square root and the Freeman-Tukey double arcsine transformation. We compared the performance of the proposed methods with the standard method through simulations using several performance measures. The simulation results showed that our proposed methods performed better than the standard LMM in terms of bias, root mean square error, and coverage probability in most of the scenarios, even when data were generated assuming the standard LMM. We also illustrated the methods using two real data sets. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of modeling approaches for carbon partitioning: Impact on estimates of global net primary production and equilibrium biomass of woody vegetation from MODIS GPP

NASA Astrophysics Data System (ADS)

Ise, Takeshi; Litton, Creighton M.; Giardina, Christian P.; Ito, Akihiko

2010-12-01

Partitioning of gross primary production (GPP) to aboveground versus belowground, to growth versus respiration, and to short versus long-lived tissues exerts a strong influence on ecosystem structure and function, with potentially large implications for the global carbon budget. A recent meta-analysis of forest ecosystems suggests that carbon partitioning to leaves, stems, and roots varies consistently with GPP and that the ratio of net primary production (NPP) to GPP is conservative across environmental gradients. To examine influences of carbon partitioning schemes employed by global ecosystem models, we used this meta-analysis-based model and a satellite-based (MODIS) terrestrial GPP data set to estimate global woody NPP and equilibrium biomass, and then compared it to two process-based ecosystem models (Biome-BGC and VISIT) using the same GPP data set. We hypothesized that different carbon partitioning schemes would result in large differences in global estimates of woody NPP and equilibrium biomass. Woody NPP estimated by Biome-BGC and VISIT was 25% and 29% higher than the meta-analysis-based model for boreal forests, with smaller differences in temperate and tropics. Global equilibrium woody biomass, calculated from model-specific NPP estimates and a single set of tissue turnover rates, was 48 and 226 Pg C higher for Biome-BGC and VISIT compared to the meta-analysis-based model, reflecting differences in carbon partitioning to structural versus metabolically active tissues. In summary, we found that different carbon partitioning schemes resulted in large variations in estimates of global woody carbon flux and storage, indicating that stand-level controls on carbon partitioning are not yet accurately represented in ecosystem models.

Students' Decision Steps in Meta-Cognitive Learning in Free Online Groups (MetaL-FrOG): A Case Study

ERIC Educational Resources Information Center

Sen Fa, Kinsley Ng; Hussin, Firuz Hussin

2011-01-01

What prompts the students to respond in online dialogic discussion? Why some students chose to fall out? This case study through the lens of phenomenography observation attempts to explain the five decision steps of students to respond in Meta-cognitive Learning in Free Online Groups (MetaL-FrOG) discussion. It presents a part of a research…

Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis.

PubMed

Dodge, Jason E; Covens, Allan L; Lacchetti, Christina; Elit, Laurie M; Le, Tien; Devries-Aboud, Michaela; Fung-Kee-Fung, Michael

2012-07-01

To systematically review the existing literature in order to determine the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer. A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of a 2004 AHRQ systematic review on the topic, searches of MEDLINE for studies published since 2004 was also conducted to update and supplement the evidentiary base. A bivariate, random-effects meta-regression model was used to produce summary estimates of sensitivity and specificity and to plot summary ROC curves with 95% confidence regions. Four meta-analyses and 53 primary studies were included in this review. The diagnostic performance of each technology was compared and contrasted based on the summary data on sensitivity and specificity obtained from the meta-analysis. Results suggest that 3D ultrasonography has both a higher sensitivity and specificity when compared to 2D ultrasound. Established morphological scoring systems also performed with respectable sensitivity and specificity, each with equivalent diagnostic competence. Explicit scoring systems did not perform as well as other diagnostic testing methods. Assessment of an adnexal mass by colour Doppler technology was neither as sensitive nor as specific as simple ultrasonography. Of the three imaging modalities considered, MRI appeared to perform the best, although results were not statistically different from CT. PET did not perform as well as either MRI or CT. The measurement of the CA-125 tumour marker appears to be less reliable than do other available assessment methods. The best available evidence was collected and included in this rigorous systematic review and meta-analysis. The abundant evidentiary base provided the context and direction for the diagnosis of early-staged ovarian cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Conducting a meta-ethnography of qualitative literature: lessons learnt.

PubMed

Atkins, Salla; Lewin, Simon; Smith, Helen; Engel, Mark; Fretheim, Atle; Volmink, Jimmy

2008-04-16

Qualitative synthesis has become more commonplace in recent years. Meta-ethnography is one of several methods for synthesising qualitative research and is being used increasingly within health care research. However, many aspects of the steps in the process remain ill-defined. We utilized the seven stages of the synthesis process to synthesise qualitative research on adherence to tuberculosis treatment. In this paper we discuss the methodological and practical challenges faced; of particular note are the methods used in our synthesis, the additional steps that we found useful in clarifying the process, and the key methodological challenges encountered in implementing the meta-ethnographic approach. The challenges included shaping an appropriate question for the synthesis; identifying relevant studies; assessing the quality of the studies; and synthesising findings across a very large number of primary studies from different contexts and research traditions. We offer suggestions that may assist in undertaking meta-ethnographies in the future. Meta-ethnography is a useful method for synthesising qualitative research and for developing models that interpret findings across multiple studies. Despite its growing use in health research, further research is needed to address the wide range of methodological and epistemological questions raised by the approach.

Conducting a meta-ethnography of qualitative literature: Lessons learnt

PubMed Central

Atkins, Salla; Lewin, Simon; Smith, Helen; Engel, Mark; Fretheim, Atle; Volmink, Jimmy

2008-01-01

Background Qualitative synthesis has become more commonplace in recent years. Meta-ethnography is one of several methods for synthesising qualitative research and is being used increasingly within health care research. However, many aspects of the steps in the process remain ill-defined. Discussion We utilized the seven stages of the synthesis process to synthesise qualitative research on adherence to tuberculosis treatment. In this paper we discuss the methodological and practical challenges faced; of particular note are the methods used in our synthesis, the additional steps that we found useful in clarifying the process, and the key methodological challenges encountered in implementing the meta-ethnographic approach. The challenges included shaping an appropriate question for the synthesis; identifying relevant studies; assessing the quality of the studies; and synthesising findings across a very large number of primary studies from different contexts and research traditions. We offer suggestions that may assist in undertaking meta-ethnographies in the future. Summary Meta-ethnography is a useful method for synthesising qualitative research and for developing models that interpret findings across multiple studies. Despite its growing use in health research, further research is needed to address the wide range of methodological and epistemological questions raised by the approach. PMID:18416812

Guidance for the utility of linear models in meta-analysis of genetic association studies of binary phenotypes.

PubMed

Cook, James P; Mahajan, Anubha; Morris, Andrew P

2017-02-01

Linear mixed models are increasingly used for the analysis of genome-wide association studies (GWAS) of binary phenotypes because they can efficiently and robustly account for population stratification and relatedness through inclusion of random effects for a genetic relationship matrix. However, the utility of linear (mixed) models in the context of meta-analysis of GWAS of binary phenotypes has not been previously explored. In this investigation, we present simulations to compare the performance of linear and logistic regression models under alternative weighting schemes in a fixed-effects meta-analysis framework, considering designs that incorporate variable case-control imbalance, confounding factors and population stratification. Our results demonstrate that linear models can be used for meta-analysis of GWAS of binary phenotypes, without loss of power, even in the presence of extreme case-control imbalance, provided that one of the following schemes is used: (i) effective sample size weighting of Z-scores or (ii) inverse-variance weighting of allelic effect sizes after conversion onto the log-odds scale. Our conclusions thus provide essential recommendations for the development of robust protocols for meta-analysis of binary phenotypes with linear models.

Television watching and risk of childhood obesity: a meta-analysis.

PubMed

Zhang, Gang; Wu, Lei; Zhou, Lingling; Lu, Weifeng; Mao, Chunting

2016-02-01

Over the last few decades, there has been a worldwide epidemic of childhood obesity. An important step in successful prevention in paediatrics is the identification of modifiable risk factors of childhood obesity. Many studies have evaluated the associations between television (TV) watching and childhood obesity but yielded inconsistent results. To help elucidate the role of TV watching, PubMed and Embase databases were searched for published studies on associations between TV watching and childhood obesity. Random-effects models and dose-response meta-analyses were used to pool study results. Fourteen cross-sectional studies with 24 reports containing 106 169 subjects were included in the meta-analysis. Subgroup analyses were conducted by the available characteristics of studies and participants. The multivariable-adjusted overall OR of the childhood obesity for the highest vs. the lowest time of TV watching was 1.47 [95% confidence interval (95% CI): 1.33-1.62]. A linear dose-response relationship was also found for TV watching and childhood obesity (P < 0.001), and the risk increased by 13% for each 1 h/day increment in TV watching. Subgroup analysis showed a basically consistent result with the overall analysis. The association is observed in both boys and girls (for boys, OR 1.30, 95% CI 1.16-1.45; for girls, OR 1.26, 95% CI 1.11-1.41). our meta-analysis suggested that increased TV watching is associated with increased risk of childhood obesity. And restricting TV time and other sedentary behaviour of children may be an important public health strategy to prevent childhood obesity. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Random-effects meta-analysis: the number of studies matters.

PubMed

Guolo, Annamaria; Varin, Cristiano

2017-06-01

This paper investigates the impact of the number of studies on meta-analysis and meta-regression within the random-effects model framework. It is frequently neglected that inference in random-effects models requires a substantial number of studies included in meta-analysis to guarantee reliable conclusions. Several authors warn about the risk of inaccurate results of the traditional DerSimonian and Laird approach especially in the common case of meta-analysis involving a limited number of studies. This paper presents a selection of likelihood and non-likelihood methods for inference in meta-analysis proposed to overcome the limitations of the DerSimonian and Laird procedure, with a focus on the effect of the number of studies. The applicability and the performance of the methods are investigated in terms of Type I error rates and empirical power to detect effects, according to scenarios of practical interest. Simulation studies and applications to real meta-analyses highlight that it is not possible to identify an approach uniformly superior to alternatives. The overall recommendation is to avoid the DerSimonian and Laird method when the number of meta-analysis studies is modest and prefer a more comprehensive procedure that compares alternative inferential approaches. R code for meta-analysis according to all of the inferential methods examined in the paper is provided.

Random-Effects Models for Meta-Analytic Structural Equation Modeling: Review, Issues, and Illustrations

ERIC Educational Resources Information Center

Cheung, Mike W.-L.; Cheung, Shu Fai

2016-01-01

Meta-analytic structural equation modeling (MASEM) combines the techniques of meta-analysis and structural equation modeling for the purpose of synthesizing correlation or covariance matrices and fitting structural equation models on the pooled correlation or covariance matrix. Both fixed-effects and random-effects models can be defined in MASEM.…

Inference for binomial probability based on dependent Bernoulli random variables with applications to meta-analysis and group level studies.

PubMed

Bakbergenuly, Ilyas; Kulinskaya, Elena; Morgenthaler, Stephan

2016-07-01

We study bias arising as a result of nonlinear transformations of random variables in random or mixed effects models and its effect on inference in group-level studies or in meta-analysis. The findings are illustrated on the example of overdispersed binomial distributions, where we demonstrate considerable biases arising from standard log-odds and arcsine transformations of the estimated probability p̂, both for single-group studies and in combining results from several groups or studies in meta-analysis. Our simulations confirm that these biases are linear in ρ, for small values of ρ, the intracluster correlation coefficient. These biases do not depend on the sample sizes or the number of studies K in a meta-analysis and result in abysmal coverage of the combined effect for large K. We also propose bias-correction for the arcsine transformation. Our simulations demonstrate that this bias-correction works well for small values of the intraclass correlation. The methods are applied to two examples of meta-analyses of prevalence. © 2016 The Authors. Biometrical Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals†

PubMed Central

Rivera, Margarita; Locke, Adam E.; Corre, Tanguy; Czamara, Darina; Wolf, Christiane; Ching-Lopez, Ana; Milaneschi, Yuri; Kloiber, Stefan; Cohen-Woods, Sara; Rucker, James; Aitchison, Katherine J.; Bergmann, Sven; Boomsma, Dorret I.; Craddock, Nick; Gill, Michael; Holsboer, Florian; Hottenga, Jouke-Jan; Korszun, Ania; Kutalik, Zoltan; Lucae, Susanne; Maier, Wolfgang; Mors, Ole; Müller-Myhsok, Bertram; Owen, Michael J.; Penninx, Brenda W. J. H.; Preisig, Martin; Rice, John; Rietschel, Marcella; Tozzi, Federica; Uher, Rudolf; Vollenweider, Peter; Waeber, Gerard; Willemsen, Gonneke; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; Breen, Gerome; McGuffin, Peter

2017-01-01

Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT. Results In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO. Conclusions This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression. PMID:28642257

Self-narrative reconstruction in emotion-focused therapy: A preliminary task analysis.

PubMed

Cunha, Carla; Mendes, Inês; Ribeiro, António P; Angus, Lynne; Greenberg, Leslie S; Gonçalves, Miguel M

2017-11-01

This research explored the consolidation phase of emotion-focused therapy (EFT) for depression and studies-through a task-analysis method-how client-therapist dyads evolved from the exploration of the problem to self-narrative reconstruction. Innovative moments (IMs) were used to situate the process of self-narrative reconstruction within sessions, particularly through reconceptualization and performing change IMs. We contrasted the observation of these occurrences with a rational model of self-narrative reconstruction, previously built. This study presents the rational model and the revised rational-empirical model of the self-narrative reconstruction task in three EFT dyads, suggesting nine steps necessary for task resolution: (1) Explicit recognition of differences in the present and steps in the path of change; (2) Development of a meta-perspective contrast between present self and past self; (3) Amplification of contrast in the self; (4) A positive appreciation of changes is conveyed; (5) Occurrence of feelings of empowerment, competence, and mastery; (6) Reference to difficulties still present; (7) Emphasis on the loss of centrality of the problem; (8) Perception of change as a gradual, developing process; and (9) Reference to projects, experiences of change, or elaboration of new plans. Central aspects of therapist activity in facilitating the client's progression along these nine steps are also elaborated.

CDMetaPOP: An individual-based, eco-evolutionary model for spatially explicit simulation of landscape demogenetics

USGS Publications Warehouse

Landguth, Erin L; Bearlin, Andrew; Day, Casey; Dunham, Jason B.

2016-01-01

1. Combining landscape demographic and genetics models offers powerful methods for addressing questions for eco-evolutionary applications.2. Using two illustrative examples, we present Cost–Distance Meta-POPulation, a program to simulate changes in neutral and/or selection-driven genotypes through time as a function of individual-based movement, complex spatial population dynamics, and multiple and changing landscape drivers.3. Cost–Distance Meta-POPulation provides a novel tool for questions in landscape genetics by incorporating population viability analysis, while linking directly to conservation applications.

Care management for Type 2 diabetes in the United States: a systematic review and meta-analysis.

PubMed

Egginton, Jason S; Ridgeway, Jennifer L; Shah, Nilay D; Balasubramaniam, Saranya; Emmanuel, Joann R; Prokop, Larry J; Montori, Victor M; Murad, Mohammad Hassan

2012-03-22

This systematic review and meta-analysis aims at assessing the composition and performance of care management models evaluated in the last decade and their impact on patient important outcomes. A comprehensive literature search of electronic bibliographic databases was performed to identify care management trials in type 2 diabetes. Random effects meta-analysis was used when feasible to pool outcome measures. Fifty-two studies were eligible. Most commonly reported were surrogate outcomes (such as HbA1c and LDL), followed by process measures (clinic visit or testing frequency). Less frequently reported were quality of life, patient satisfaction, self-care, and healthcare utilization. Most care management modalities were carved out from primary care. Meta-analysis demonstrated a statistically significant but trivial reduction of HbA1c (weighted difference in means -0.21%, 95% confidence interval -0.40 to -0.03, p < .03) and LDL-cholesterol (weighted difference in means -3.38 mg/dL, 95% confidence interval -6.27 to -0.49, p < .02). Most care management programs for patients with type 2 diabetes are 'carved-out', accomplish limited effects on metabolic outcomes, and have unknown effects on patient important outcomes. Comparative effectiveness research of different models of care management is needed to inform the design of medical homes for patients with chronic conditions.

A meta-model based approach for rapid formability estimation of continuous fibre reinforced components

NASA Astrophysics Data System (ADS)

Zimmerling, Clemens; Dörr, Dominik; Henning, Frank; Kärger, Luise

2018-05-01

Due to their high mechanical performance, continuous fibre reinforced plastics (CoFRP) become increasingly important for load bearing structures. In many cases, manufacturing CoFRPs comprises a forming process of textiles. To predict and optimise the forming behaviour of a component, numerical simulations are applied. However, for maximum part quality, both the geometry and the process parameters must match in mutual regard, which in turn requires numerous numerically expensive optimisation iterations. In both textile and metal forming, a lot of research has focused on determining optimum process parameters, whilst regarding the geometry as invariable. In this work, a meta-model based approach on component level is proposed, that provides a rapid estimation of the formability for variable geometries based on pre-sampled, physics-based draping data. Initially, a geometry recognition algorithm scans the geometry and extracts a set of doubly-curved regions with relevant geometry parameters. If the relevant parameter space is not part of an underlying data base, additional samples via Finite-Element draping simulations are drawn according to a suitable design-table for computer experiments. Time saving parallel runs of the physical simulations accelerate the data acquisition. Ultimately, a Gaussian Regression meta-model is built from the data base. The method is demonstrated on a box-shaped generic structure. The predicted results are in good agreement with physics-based draping simulations. Since evaluations of the established meta-model are numerically inexpensive, any further design exploration (e.g. robustness analysis or design optimisation) can be performed in short time. It is expected that the proposed method also offers great potential for future applications along virtual process chains: For each process step along the chain, a meta-model can be set-up to predict the impact of design variations on manufacturability and part performance. Thus, the method is considered to facilitate a lean and economic part and process design under consideration of manufacturing effects.

Comparison of intra-articular hyaluronic acid and methylprednisolone for pain management in knee osteoarthritis: A meta-analysis of randomized controlled trials.

PubMed

Ran, Jian; Yang, Xiaohui; Ren, Zheng; Wang, Jian; Dong, Hui

2018-05-01

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of intra-articular methylprednisolone and hyaluronic acid (HA) in term of pain reduction and improvements of knee function in patients with knee osteoarthritis (OA). The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving HA and methylprednisolone in knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 14.0. Five RCTs with 1004 patients were included in the meta-analysis. The present meta-analysis indicated that there were no significant differences in terms of WOMAC pain, physical function and stiffness at 4 week, 12 weeks and 26 weeks between HA and methylprednisolone groups. No increased risk of adverse events were identified in both groups. Both HA and methylprednisolone injections were effective therapies for patients with knee OA. Methylprednisolone showed comparable efficacy in reducing pain and improving functional recovery to HA. And no significant difference was found in long-term of follow-up in terms of adverse effects. Copyright © 2018 IJS Publishing Group Ltd. All rights reserved.

Composite Materials and Meta Materials for a New Approach to ITER ICRH Loads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bottollier-Curtet, H.; Argouarch, A.; Vulliez, K.

Preliminary laboratory testing of ICRH antennas is a very useful step before their commissioning. Traditionally, pure water, salt water or baking soda water loads are used. These 'water' loads are convenient but strongly limited in terms of performance testing. We have started two feasibility studies for advanced ICRH loads made of ferroelectric ceramics (passive loads) and meta materials (active loads). Preliminary results are very encouraging.

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

PubMed Central

2014-01-01

Introduction A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy. Methods Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis. Conclusion Our results suggest a role of PPARG gene in the development of SSc. PMID:24401602

Video Game Acceptance: A Meta-Analysis of the Extended Technology Acceptance Model.

PubMed

Wang, Xiaohui; Goh, Dion Hoe-Lian

2017-11-01

The current study systematically reviews and summarizes the existing literature of game acceptance, identifies the core determinants, and evaluates the strength of the relationships in the extended technology acceptance model. Moreover, this study segments video games into two categories: hedonic and utilitarian and examines player acceptance of these two types separately. Through a meta-analysis of 50 articles, we find that perceived ease of use (PEOU), perceived usefulness (PU), and perceived enjoyment (PE) significantly associate with attitude and behavioral intention. PE is the dominant predictor of hedonic game acceptance, while PEOU and PU are the main determinants of utilitarian game acceptance. Furthermore, we find that respondent type and game platform are significant moderators. Findings of this study provide critical insights into the phenomenon of game acceptance and suggest directions for future research.

BioMaS: a modular pipeline for Bioinformatic analysis of Metagenomic AmpliconS.

PubMed

Fosso, Bruno; Santamaria, Monica; Marzano, Marinella; Alonso-Alemany, Daniel; Valiente, Gabriel; Donvito, Giacinto; Monaco, Alfonso; Notarangelo, Pasquale; Pesole, Graziano

2015-07-01

Substantial advances in microbiology, molecular evolution and biodiversity have been carried out in recent years thanks to Metagenomics, which allows to unveil the composition and functions of mixed microbial communities in any environmental niche. If the investigation is aimed only at the microbiome taxonomic structure, a target-based metagenomic approach, here also referred as Meta-barcoding, is generally applied. This approach commonly involves the selective amplification of a species-specific genetic marker (DNA meta-barcode) in the whole taxonomic range of interest and the exploration of its taxon-related variants through High-Throughput Sequencing (HTS) technologies. The accessibility to proper computational systems for the large-scale bioinformatic analysis of HTS data represents, currently, one of the major challenges in advanced Meta-barcoding projects. BioMaS (Bioinformatic analysis of Metagenomic AmpliconS) is a new bioinformatic pipeline designed to support biomolecular researchers involved in taxonomic studies of environmental microbial communities by a completely automated workflow, comprehensive of all the fundamental steps, from raw sequence data upload and cleaning to final taxonomic identification, that are absolutely required in an appropriately designed Meta-barcoding HTS-based experiment. In its current version, BioMaS allows the analysis of both bacterial and fungal environments starting directly from the raw sequencing data from either Roche 454 or Illumina HTS platforms, following two alternative paths, respectively. BioMaS is implemented into a public web service available at https://recasgateway.ba.infn.it/ and is also available in Galaxy at http://galaxy.cloud.ba.infn.it:8080 (only for Illumina data). BioMaS is a friendly pipeline for Meta-barcoding HTS data analysis specifically designed for users without particular computing skills. A comparative benchmark, carried out by using a simulated dataset suitably designed to broadly represent the currently known bacterial and fungal world, showed that BioMaS outperforms QIIME and MOTHUR in terms of extent and accuracy of deep taxonomic sequence assignments.

Reading in the brain of children and adults: a meta-analysis of 40 functional magnetic resonance imaging studies.

PubMed

Martin, Anna; Schurz, Matthias; Kronbichler, Martin; Richlan, Fabio

2015-05-01

We used quantitative, coordinate-based meta-analysis to objectively synthesize age-related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23-34 years) were matched to 20 studies with children (age means: 7-12 years). The separate meta-analyses of these two sets showed a pattern of reading-related brain activation common to children and adults in left ventral occipito-temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta-analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading-related activation clusters in children and adults are provided. © 2015 Wiley Periodicals, Inc.

A Meta-Meta-Analysis: Empirical Review of Statistical Power, Type I Error Rates, Effect Sizes, and Model Selection of Meta-Analyses Published in Psychology

ERIC Educational Resources Information Center

Cafri, Guy; Kromrey, Jeffrey D.; Brannick, Michael T.

2010-01-01

This article uses meta-analyses published in "Psychological Bulletin" from 1995 to 2005 to describe meta-analyses in psychology, including examination of statistical power, Type I errors resulting from multiple comparisons, and model choice. Retrospective power estimates indicated that univariate categorical and continuous moderators, individual…

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

PubMed Central

2011-01-01

Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

Should in-line filters be used in peripheral intravenous catheters to prevent infusion-related phlebitis? A systematic review of randomized controlled trials.

PubMed

Niël-Weise, Barbara S; Stijnen, Theo; van den Broek, Peterhans J

2010-06-01

In this systematic review, we assessed the effect of in-line filters on infusion-related phlebitis associated with peripheral IV catheters. The study was designed as a systematic review and meta-analysis of randomized controlled trials. We used MEDLINE and the Cochrane Controlled Trial Register up to August 10, 2009. Two reviewers independently assessed trial quality and extracted data. Data on phlebitis were combined when appropriate, using a random-effects model. The impact of the risk of phlebitis in the control group (baseline risk) on the effect of in-line filters was studied by using meta-regression based on the bivariate meta-analysis model. The quality of the evidence was determined by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. Eleven trials (1633 peripheral catheters) were included in this review to compare the effect of in-line filters on the incidence of phlebitis in hospitalized patients. Baseline risks across trials ranged from 23% to 96%. Meta-analysis of all trials showed that in-line filters reduced the risk of infusion-related phlebitis (relative risk, 0.66; 95% confidence interval, 0.43-1.00). This benefit, however, is very uncertain, because the trials had serious methodological shortcomings and meta-analysis revealed marked unexplained statistical heterogeneity (P < 0.0000, I(2) = 90.4%). The estimated benefit did not depend on baseline risk. In-line filters in peripheral IV catheters cannot be recommended routinely, because evidence of their benefit is uncertain.

Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma.

PubMed

Cucchetti, Alessandro; Piscaglia, Fabio; Cescon, Matteo; Colecchia, Antonio; Ercolani, Giorgio; Bolondi, Luigi; Pinna, Antonio D

2013-08-01

Both hepatic resection and radiofrequency ablation (RFA) are considered curative treatments for hepatocellular carcinoma (HCC), but their economic impact still remains not determined. Aim of the present study was to analyze the cost-effectiveness (CE) of these two strategies in early stage HCC (Milan criteria). As first step, a meta-analysis of the pertinent literature of the last decade was performed. Seventeen studies fulfilled the inclusion criteria: 3996 patients underwent resection and 4424 underwent RFA for early HCC. Data obtained from the meta-analysis were used to construct a Markov model. Costs were assessed from the health care provider perspective. A Monte Carlo probabilistic sensitivity analysis was used to estimate outcomes with distribution samples of 1000 patients for each treatment arm. In a 10-year perspective, for very early HCC (single nodule <2 cm) in Child-Pugh class A patients, RFA provided similar life-expectancy and quality-adjusted life-expectancy at a lower cost than resection and was the most cost-effective therapeutic strategy. For single HCCs of 3-5 cm, resection provided better life-expectancy and was more cost-effective than RFA, at a willingness-to-pay above €4200 per quality-adjusted life-year. In the presence of two or three nodules ≤3 cm, life-expectancy and quality-adjusted life-expectancy were very similar between the two treatments, but cost-effectiveness was again in favour of RFA. For very early HCC and in the presence of two or three nodules ≤3 cm, RFA is more cost-effective than resection; for single larger early stage HCCs, surgical resection remains the best strategy to adopt as a result of better survival rates at an acceptable increase in cost. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Dietary Magnesium Intake and Metabolic Syndrome in the Adult Population: Dose-Response Meta-Analysis and Meta-Regression

PubMed Central

Ju, Sang-Yhun; Choi, Whan-Seok; Ock, Sun-Myeong; Kim, Chul-Min; Kim, Do-Hoon

2014-01-01

Increasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs) for metabolic syndrome in ≥3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84–0.93; I2 = 36.3%). The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day) and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome. PMID:25533010

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

PubMed

Krebs, Teri S; Johansen, Pål-Ørjan

2012-07-01

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

Less is less: a systematic review of graph use in meta-analyses.

PubMed

Schild, Anne H E; Voracek, Martin

2013-09-01

Graphs are an essential part of scientific communication. Complex datasets, of which meta-analyses are textbook examples, benefit the most from visualization. Although a number of graph options for meta-analyses exist, the extent to which these are used was hitherto unclear. A systematic review on graph use in meta-analyses in three disciplines (medicine, psychology, and business) and nine journals was conducted. Interdisciplinary differences, which are mirrored in the respective journals, were revealed, that is, graph use correlates with external factors rather than methodological considerations. There was only limited variation in graph types (with forest plots as the most important representatives), and diagnostic plots were very rare. Although an increase in graph use over time could be observed, it is unlikely that this phenomenon is specific to meta-analyses. There is a gaping discrepancy between available graphic methods and their application in meta-analyses. This may be rooted in a number of factors, namely, (i) insufficient dissemination of new developments, (ii) unsatisfactory implementation in software packages, and (iii) minor attention on graphics in meta-analysis reporting guidelines. Using visualization methods to their full capacity is a further step in using meta-analysis to its full potential. Copyright © 2013 John Wiley & Sons, Ltd.

The Success of Linear Bootstrapping Models: Decision Domain-, Expertise-, and Criterion-Specific Meta-Analysis

PubMed Central

Kaufmann, Esther; Wittmann, Werner W.

2016-01-01

The success of bootstrapping or replacing a human judge with a model (e.g., an equation) has been demonstrated in Paul Meehl’s (1954) seminal work and bolstered by the results of several meta-analyses. To date, however, analyses considering different types of meta-analyses as well as the potential dependence of bootstrapping success on the decision domain, the level of expertise of the human judge, and the criterion for what constitutes an accurate decision have been missing from the literature. In this study, we addressed these research gaps by conducting a meta-analysis of lens model studies. We compared the results of a traditional (bare-bones) meta-analysis with findings of a meta-analysis of the success of bootstrap models corrected for various methodological artifacts. In line with previous studies, we found that bootstrapping was more successful than human judgment. Furthermore, bootstrapping was more successful in studies with an objective decision criterion than in studies with subjective or test score criteria. We did not find clear evidence that the success of bootstrapping depended on the decision domain (e.g., education or medicine) or on the judge’s level of expertise (novice or expert). Correction of methodological artifacts increased the estimated success of bootstrapping, suggesting that previous analyses without artifact correction (i.e., traditional meta-analyses) may have underestimated the value of bootstrapping models. PMID:27327085

Fitting Meta-Analytic Structural Equation Models with Complex Datasets

ERIC Educational Resources Information Center

Wilson, Sandra Jo; Polanin, Joshua R.; Lipsey, Mark W.

2016-01-01

A modification of the first stage of the standard procedure for two-stage meta-analytic structural equation modeling for use with large complex datasets is presented. This modification addresses two common problems that arise in such meta-analyses: (a) primary studies that provide multiple measures of the same construct and (b) the correlation…

The RTEL1 rs6010620 polymorphism and glioma risk: a meta-analysis based on 12 case-control studies.

PubMed

Du, Shu-Li; Geng, Ting-Ting; Feng, Tian; Chen, Cui-Ping; Jin, Tian-Bo; Chen, Chao

2014-01-01

The association between the RTEL1 rs6010620 single nucleotide polymorphism (SNP) and glioma risk has been extensively studied. However, the results remain inconclusive. To further examine this association, we performed a meta-analysis. A computerized search of the PubMed and Embase databases for publications regarding the RTEL1 rs6010620 polymorphism and glioma cancer risk was performed. Genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analyses, tests of heterogeneity, cumulative meta-analyses, and assessments of bias were performed in our meta-analysis. Our meta-analysis confirmed that risk with allele A is lower than with allele G for glioma. The A allele of rs6010620 in RTEL1 decreased the risk of developing glioma in the 12 case-control studies for all genetic models: the allele model (OR=0.752, 95%CI: 0.715-0.792), the dominant model (OR=0.729, 95%CI: 0.685-0.776), the recessive model (OR=0.647, 95%CI: 0.569-0.734), the homozygote comparison (OR=0.528, 95%CI: 0.456-0.612), and the heterozygote comparison (OR=0.761, 95%CI: 0.713-0.812). In all genetic models, the association between the RTEL1 rs6010620 polymorphism and glioma risk was significant. This meta-analysis suggests that the RTEL1 rs6010620 polymorphism may be a risk factor for glioma. Further functional studies evaluating this polymorphism and glioma risk are warranted.

Meta-Analysis for Primary and Secondary Data Analysis: The Super-Experiment Metaphor.

ERIC Educational Resources Information Center

Jackson, Sally

1991-01-01

Considers the relation between meta-analysis statistics and analysis of variance statistics. Discusses advantages and disadvantages as a primary data analysis tool. Argues that the two approaches are partial paraphrases of one another. Advocates an integrative approach that introduces the best of meta-analytic thinking into primary analysis…

Explaining the heterogeneous scrapie surveillance figures across Europe: a meta-regression approach.

PubMed

Del Rio Vilas, Victor J; Hopp, Petter; Nunes, Telmo; Ru, Giuseppe; Sivam, Kumar; Ortiz-Pelaez, Angel

2007-06-28

Two annual surveys, the abattoir and the fallen stock, monitor the presence of scrapie across Europe. A simple comparison between the prevalence estimates in different countries reveals that, in 2003, the abattoir survey appears to detect more scrapie in some countries. This is contrary to evidence suggesting the greater ability of the fallen stock survey to detect the disease. We applied meta-analysis techniques to study this apparent heterogeneity in the behaviour of the surveys across Europe. Furthermore, we conducted a meta-regression analysis to assess the effect of country-specific characteristics on the variability. We have chosen the odds ratios between the two surveys to inform the underlying relationship between them and to allow comparisons between the countries under the meta-regression framework. Baseline risks, those of the slaughtered populations across Europe, and country-specific covariates, available from the European Commission Report, were inputted in the model to explain the heterogeneity. Our results show the presence of significant heterogeneity in the odds ratios between countries and no reduction in the variability after adjustment for the different risks in the baseline populations. Three countries contributed the most to the overall heterogeneity: Germany, Ireland and The Netherlands. The inclusion of country-specific covariates did not, in general, reduce the variability except for one variable: the proportion of the total adult sheep population sampled as fallen stock by each country. A large residual heterogeneity remained in the model indicating the presence of substantial effect variability between countries. The meta-analysis approach was useful to assess the level of heterogeneity in the implementation of the surveys and to explore the reasons for the variation between countries.

Does Bruxism Contribute to Dental Implant Failure? A Systematic Review and Meta-Analysis.

PubMed

Zhou, Yi; Gao, Jinxia; Luo, Le; Wang, Yining

2016-04-01

Bruxism was usually considered as a contraindication for oral implanting. The causal relationship between bruxism and dental implant failure was remained controversial in existing literatures. This meta-analysis was performed to investigate the relationship between them. This review conducted an electronic systematic literature search in MEDLINE (PubMed) and EmBase in November 2013 without time and language restrictions. Meanwhile, a hand searching for all the relevant references of included studies was also conducted. Study information extraction and methodological quality assessments were accomplished by two reviewers independently. A discussion ensued if any disagreement occurred, and unresolved issues were solved by consulting a third reviewer. Methodological quality was assessed by using the Newcastle-Ottawa Scale tool. Odds ratio (OR) with 95% confidence interval (CI) was pooled to estimate the relative effect of bruxism on dental implant failures. Fixed effects model was used initially; if the heterogeneity was high, random effects model was chosen for meta-analysis. Statistical analyses were carried out by using Review Manager 5.1. In this meta-analysis review, extracted data were classified into two groups based on different units. Units were based on the number of prostheses (group A) and the number of patients (group B). In group A, the total pooled OR of bruxers versus nonbruxers for all subgroups was 4.72 (95% CI: 2.66-8.36, p = .07). In group B, the total pooled OR of bruxers versus nonbruxers for all subgroups was 3.83 (95% CI: 2.12-6.94, p = .22). This meta-analysis was performed to evaluate the relationship between bruxism and dental implant failure. In contrast to nonbruxers, prostheses in bruxers had a higher failure rate. It suggests that bruxism is a contributing factor of causing the occurrence of dental implant technical/biological complications and plays a role in dental implant failure. © 2015 Wiley Periodicals, Inc.

CrossFit Overview: Systematic Review and Meta-analysis.

PubMed

Claudino, João Gustavo; Gabbett, Tim J; Bourgeois, Frank; Souza, Helton de Sá; Miranda, Rafael Chagas; Mezêncio, Bruno; Soncin, Rafael; Cardoso Filho, Carlos Alberto; Bottaro, Martim; Hernandez, Arnaldo Jose; Amadio, Alberto Carlos; Serrão, Julio Cerca

2018-02-26

CrossFit is recognized as one of the fastest growing high-intensity functional training modes in the world. However, scientific data regarding the practice of CrossFit is sparse. Therefore, the objective of this study is to analyze the findings of scientific literature related to CrossFit via systematic review and meta-analysis. Systematic searches of the PubMed, Web of Science, Scopus, Bireme/MedLine, and SciELO online databases were conducted for articles reporting the effects of CrossFit training. The systematic review followed the PRISMA guidelines. The Oxford Levels of Evidence was used for all included articles, and only studies that investigated the effects of CrossFit as a training program were included in the meta-analysis. For the meta-analysis, effect sizes (ESs) with 95% confidence interval (CI) were calculated and heterogeneity was assessed using a random-effects model. Thirty-one articles were included in the systematic review and four were included in the meta-analysis. However, only two studies had a high level of evidence at low risk of bias. Scientific literature related to CrossFit has reported on body composition, psycho-physiological parameters, musculoskeletal injury risk, life and health aspects, and psycho-social behavior. In the meta-analysis, significant results were not found for any variables. The current scientific literature related to CrossFit has few studies with high level of evidence at low risk of bias. However, preliminary data has suggested that CrossFit practice is associated with higher levels of sense of community, satisfaction, and motivation.

Meta-Analytic Structural Equation Modeling (MASEM): Comparison of the Multivariate Methods

ERIC Educational Resources Information Center

Zhang, Ying

2011-01-01

Meta-analytic Structural Equation Modeling (MASEM) has drawn interest from many researchers recently. In doing MASEM, researchers usually first synthesize correlation matrices across studies using meta-analysis techniques and then analyze the pooled correlation matrix using structural equation modeling techniques. Several multivariate methods of…

Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2.

PubMed

Hoaglin, David C; Hawkins, Neil; Jansen, Jeroen P; Scott, David A; Itzler, Robbin; Cappelleri, Joseph C; Boersma, Cornelis; Thompson, David; Larholt, Kay M; Diaz, Mireya; Barrett, Annabel

2011-06-01

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Single balloon versus double balloon bipedicular kyphoplasty: a systematic review and meta-analysis.

PubMed

Jing, Zehao; Dong, Jianli; Li, Zhengwei; Nan, Feng

2018-06-19

Kyphoplasty has been widely used to treat vertebral compression fractures (VCFs). In standard procedure of kyphoplasty, two balloons were inserted into the vertebral body through bipedicular and inflated simultaneously, while using a single balloon two times is also a common method in clinic to lessen the financial burden of patients. However, the effect and safety of single balloon versus double balloon bipedicular kyphoplasty are still controversy. In this systematic review and meta-analysis, eligible studies were identified through a comprehensive literature search of PubMed, Cochrane library EMBASE, Web of Science, Wanfang, CNKI, VIP and CBM until January 1, 2018. Results from individual studies were pooled using a random or fixed effects model. Seven articles were included in the systematic review and five studies were consisted in meta-analysis. We observed no significant difference between single balloon and double balloon bipedicular kyphoplasty in visual analog scale (VAS), angle (kyphotic angle and Cobb angle), consumption (operation time, cement volume and volume of bleeding), vertebral height (anterior height, medium height and posterior height) and complications (cement leakage and new VCFs), while the cost of single balloon bipedicular kyphoplasty is lower than that of double balloon bipedicular kyphoplasty. The results of our meta-analysis also demonstrated that single balloon can significantly improve the VAS, angle and vertebral height of patients suffering from VCFs. This systematic review and meta-analysis collectively concludes that single balloon bipedicular kyphoplasty is as effective as double balloon bipedicular kyphoplasty in improving clinical symptoms, deformity and complications of VCFs but not so expensive. These slides can be retrieved under Electronic Supplementary Material.

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making.

PubMed

Owen, Rhiannon K; Cooper, Nicola J; Quinn, Terence J; Lees, Rosalind; Sutton, Alex J

2018-07-01

Network meta-analyses (NMA) have extensively been used to compare the effectiveness of multiple interventions for health care policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whereas MMSE at threshold <25/30 appeared to have the best true negative rate. The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence.

PubMed

Forero, Diego A; López-León, Sandra; Shin, Hyoung Doo; Park, Byung Lae; Kim, Dai-Jin

2015-04-01

Alcohol-related problems have a large impact on human health, accounting for around 4% of deaths and 4.5% of disability-adjusted life-years around the world. Genetic factors could explain a significant fraction of the risk for alcohol dependence (AD). Recent meta-analyses have found significant pooled odds ratios (ORs) for variants in the ADH1B, ADH1C, DRD2 and HTR2A genes. In the present study, we carried out a meta-analysis of common variants in 6 candidate genes involved in neurotransmission and neuroplasticity: BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA. We carried out a systematic search for published association studies that analyzed the genes of interest. Relevant articles were retrieved and demographic and genetic data were extracted. Pooled ORs were calculated using a random-effects model using the Meta-Analyst program. Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity. Forty two published studies were included in the current meta-analysis: BDNF-rs6265 (nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MAOA-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity. In terms of the number of candidate genes included, this is one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Association between nutritional status and dengue infection: a systematic review and meta-analysis.

PubMed

Trang, Nguyen Thi Huyen; Long, Nguyen Phuoc; Hue, Tran Thi Minh; Hung, Le Phi; Trung, Tran Dinh; Dinh, Doan Ngoc; Luan, Nguyen Thien; Huy, Nguyen Tien; Hirayama, Kenji

2016-04-20

Dengue infection has various clinical manifestations, often with unpredictable clinical evolutions and outcomes. Several factors including nutritional status have been studied to find the relationship with dengue severity. However, the nutritional status had conflicting effects on the complication of dengue in some previous studies. Therefore, we conducted a systematic review and performed a meta-analysis to analyze the association between nutritional status and the outcome of dengue infection. Eleven electronic databases and manual searching of reference lists were used to identify the relevant studies published before August 2013. At least two authors worked independently in every step to select eligible studies and extract data. Dengue severity in the included studies must be classified into three categories: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirteen articles that met the inclusion criteria came to final analysis. A meta-analysis using fixed- or random-effects models was conducted to calculate pooled odds ratios (OR) with corresponding 95 % confidence intervals. It has shown that there was no statistically significant association between DHF group and DSS group in malnutritional and overweight/obesity patients with OR: 1.17 (95 % CI: 0.99-1.39), 1.31 (0.91-1.88), respectively. A significantly inverse relation between DF and DHF groups of malnutritional patients was revealed (OR = 0.71, 95 % CI: 0.56-0.90). Our meta-analysis also indicated a statistically significant negative correlation between malnourished children with dengue virus infection and healthy children (OR = 0.46, 95 % CI: 0.3-0.70). When analyzing patients with normal nutrition status, we found out that there was a significantly negative relationship between DHF and DSS groups (0.87; 95 % CI: 0.77-0.99). Other comparisons of DSS with DF/DHF groups, DSS/DHF with DF groups, and DHF with DF groups in normal nutritional patients showed no significant correlation. However, the findings should be interpreted cautiously because all significant associations were lost after removing of the largest study. Results from previous studies failed to show any solid consistency regarding the association between the nutritional status and dengue infection. Consequently, the effects of nutritional status on dengue disease outcome has been controversial. Further studies are recommended to clarify the impact of nutritional status on dengue infection.

Evaluation of the matrix exponential for use in ground-water-flow and solute-transport simulations; theoretical framework

USGS Publications Warehouse

Umari, A.M.; Gorelick, S.M.

1986-01-01

It is possible to obtain analytic solutions to the groundwater flow and solute transport equations if space variables are discretized but time is left continuous. From these solutions, hydraulic head and concentration fields for any future time can be obtained without ' marching ' through intermediate time steps. This analytical approach involves matrix exponentiation and is referred to as the Matrix Exponential Time Advancement (META) method. Two algorithms are presented for the META method, one for symmetric and the other for non-symmetric exponent matrices. A numerical accuracy indicator, referred to as the matrix condition number, was defined and used to determine the maximum number of significant figures that may be lost in the META method computations. The relative computational and storage requirements of the META method with respect to the time marching method increase with the number of nodes in the discretized problem. The potential greater accuracy of the META method and the associated greater reliability through use of the matrix condition number have to be weighed against this increased relative computational and storage requirements of this approach as the number of nodes becomes large. For a particular number of nodes, the META method may be computationally more efficient than the time-marching method, depending on the size of time steps used in the latter. A numerical example illustrates application of the META method to a sample ground-water-flow problem. (Author 's abstract)

Multivariate meta-analysis of individual participant data helped externally validate the performance and implementation of a prediction model.

PubMed

Snell, Kym I E; Hua, Harry; Debray, Thomas P A; Ensor, Joie; Look, Maxime P; Moons, Karel G M; Riley, Richard D

2016-01-01

Our aim was to improve meta-analysis methods for summarizing a prediction model's performance when individual participant data are available from multiple studies for external validation. We suggest multivariate meta-analysis for jointly synthesizing calibration and discrimination performance, while accounting for their correlation. The approach estimates a prediction model's average performance, the heterogeneity in performance across populations, and the probability of "good" performance in new populations. This allows different implementation strategies (e.g., recalibration) to be compared. Application is made to a diagnostic model for deep vein thrombosis (DVT) and a prognostic model for breast cancer mortality. In both examples, multivariate meta-analysis reveals that calibration performance is excellent on average but highly heterogeneous across populations unless the model's intercept (baseline hazard) is recalibrated. For the cancer model, the probability of "good" performance (defined by C statistic ≥0.7 and calibration slope between 0.9 and 1.1) in a new population was 0.67 with recalibration but 0.22 without recalibration. For the DVT model, even with recalibration, there was only a 0.03 probability of "good" performance. Multivariate meta-analysis can be used to externally validate a prediction model's calibration and discrimination performance across multiple populations and to evaluate different implementation strategies. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

A methodological systematic review of what's wrong with meta-ethnography reporting.

PubMed

France, Emma F; Ring, Nicola; Thomas, Rebecca; Noyes, Jane; Maxwell, Margaret; Jepson, Ruth

2014-11-19

Syntheses of qualitative studies can inform health policy, services and our understanding of patient experience. Meta-ethnography is a systematic seven-phase interpretive qualitative synthesis approach well-suited to producing new theories and conceptual models. However, there are concerns about the quality of meta-ethnography reporting, particularly the analysis and synthesis processes. Our aim was to investigate the application and reporting of methods in recent meta-ethnography journal papers, focusing on the analysis and synthesis process and output. Methodological systematic review of health-related meta-ethnography journal papers published from 2012-2013. We searched six electronic databases, Google Scholar and Zetoc for papers using key terms including 'meta-ethnography.' Two authors independently screened papers by title and abstract with 100% agreement. We identified 32 relevant papers. Three authors independently extracted data and all authors analysed the application and reporting of methods using content analysis. Meta-ethnography was applied in diverse ways, sometimes inappropriately. In 13% of papers the approach did not suit the research aim. In 66% of papers reviewers did not follow the principles of meta-ethnography. The analytical and synthesis processes were poorly reported overall. In only 31% of papers reviewers clearly described how they analysed conceptual data from primary studies (phase 5, 'translation' of studies) and in only one paper (3%) reviewers explicitly described how they conducted the analytic synthesis process (phase 6). In 38% of papers we could not ascertain if reviewers had achieved any new interpretation of primary studies. In over 30% of papers seminal methodological texts which could have informed methods were not cited. We believe this is the first in-depth methodological systematic review of meta-ethnography conduct and reporting. Meta-ethnography is an evolving approach. Current reporting of methods, analysis and synthesis lacks clarity and comprehensiveness. This is a major barrier to use of meta-ethnography findings that could contribute significantly to the evidence base because it makes judging their rigour and credibility difficult. To realise the high potential value of meta-ethnography for enhancing health care and understanding patient experience requires reporting that clearly conveys the methodology, analysis and findings. Tailored meta-ethnography reporting guidelines, developed through expert consensus, could improve reporting.

Meta-analysis of individual registry results enhances international registry collaboration.

PubMed

Paxton, Elizabeth W; Mohaddes, Maziar; Laaksonen, Inari; Lorimer, Michelle; Graves, Stephen E; Malchau, Henrik; Namba, Robert S; Kärrholm, John; Rolfson, Ola; Cafri, Guy

2018-03-28

Background and purpose - Although common in medical research, meta-analysis has not been widely adopted in registry collaborations. A meta-analytic approach in which each registry conducts a standardized analysis on its own data followed by a meta-analysis to calculate a weighted average of the estimates allows collaboration without sharing patient-level data. The value of meta-analysis as an alternative to individual patient data analysis is illustrated in this study by comparing the risk of revision of porous tantalum cups versus other uncemented cups in primary total hip arthroplasties from Sweden, Australia, and a US registry (2003-2015). Patients and methods - For both individual patient data analysis and meta-analysis approaches a Cox proportional hazard model was fit for time to revision, comparing porous tantalum (n = 23,201) with other uncemented cups (n = 128,321). Covariates included age, sex, diagnosis, head size, and stem fixation. In the meta-analysis approach, treatment effect size (i.e., Cox model hazard ratio) was calculated within each registry and a weighted average for the individual registries' estimates was calculated. Results - Patient-level data analysis and meta-analytic approaches yielded the same results with the porous tantalum cups having a higher risk of revision than other uncemented cups (HR (95% CI) 1.6 (1.4-1.7) and HR (95% CI) 1.5 (1.4-1.7), respectively). Adding the US cohort to the meta-analysis led to greater generalizability, increased precision of the treatment effect, and similar findings (HR (95% CI) 1.6 (1.4-1.7)) with increased risk of porous tantalum cups. Interpretation - The meta-analytic technique is a viable option to address privacy, security, and data ownership concerns allowing more expansive registry collaboration, greater generalizability, and increased precision of treatment effects.

Video game training does not enhance cognitive ability: A comprehensive meta-analytic investigation.

PubMed

Sala, Giovanni; Tatlidil, K Semir; Gobet, Fernand

2018-02-01

As a result of considerable potential scientific and societal implications, the possibility of enhancing cognitive ability by training has been one of the most influential topics of cognitive psychology in the last two decades. However, substantial research into the psychology of expertise and a recent series of meta-analytic reviews have suggested that various types of cognitive training (e.g., working memory training) benefit performance only in the trained tasks. The lack of skill generalization from one domain to different ones-that is, far transfer-has been documented in various fields of research such as working memory training, music, brain training, and chess. Video game training is another activity that has been claimed by many researchers to foster a broad range of cognitive abilities such as visual processing, attention, spatial ability, and cognitive control. We tested these claims with three random-effects meta-analytic models. The first meta-analysis (k = 310) examined the correlation between video game skill and cognitive ability. The second meta-analysis (k = 315) dealt with the differences between video game players and nonplayers in cognitive ability. The third meta-analysis (k = 359) investigated the effects of video game training on participants' cognitive ability. Small or null overall effect sizes were found in all three models. These outcomes show that overall cognitive ability and video game skill are only weakly related. Importantly, we found no evidence of a causal relationship between playing video games and enhanced cognitive ability. Video game training thus represents no exception to the general difficulty of obtaining far transfer. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Rapid On-Site Evaluation of Fine-Needle Aspiration by Non-Cytopathologists: A Systematic Review and Meta-Analysis of Diagnostic Accuracy Studies for Adequacy Assessment.

PubMed

Pearson, Lauren; Factor, Rachel E; White, Sandra K; Walker, Brandon S; Layfield, Lester J; Schmidt, Robert L

2018-06-06

Rapid on-site evaluation (ROSE) has been shown to improve adequacy rates and reduce needle passes. ROSE is often performed by cytopathologists who have limited availability and may be costlier than alternatives. Several recent studies examined the use of alternative evaluators (AEs) for ROSE. A summary of this information could help inform guidelines regarding the use of AEs. The objective was to assess the accuracy of AEs compared to cytopathologists in assessing the adequacy of specimens during ROSE. This was a systematic review and meta-analysis. Reporting and study quality were assessed using the STARD guidelines and QUADAS-2. All steps were performed independently by two evaluators. Summary estimates were obtained using the hierarchal method in Stata v14. Heterogeneity was evaluated using Higgins' I2 statistic. The systematic review identified 13 studies that were included in the meta-analysis. Summary estimates of sensitivity and specificity for AEs were 97% (95% CI: 92-99%) and 83% (95% CI: 68-92%). There was wide variation in accuracy statistics between studies (I2 = 0.99). AEs sometimes have accuracy that is close to cytopathologists. However, there is wide variability between studies, so it is not possible to provide a broad guideline regarding the use of AEs. © 2018 S. Karger AG, Basel.

Network meta-analysis, electrical networks and graph theory.

PubMed

Rücker, Gerta

2012-12-01

Network meta-analysis is an active field of research in clinical biostatistics. It aims to combine information from all randomized comparisons among a set of treatments for a given medical condition. We show how graph-theoretical methods can be applied to network meta-analysis. A meta-analytic graph consists of vertices (treatments) and edges (randomized comparisons). We illustrate the correspondence between meta-analytic networks and electrical networks, where variance corresponds to resistance, treatment effects to voltage, and weighted treatment effects to current flows. Based thereon, we then show that graph-theoretical methods that have been routinely applied to electrical networks also work well in network meta-analysis. In more detail, the resulting consistent treatment effects induced in the edges can be estimated via the Moore-Penrose pseudoinverse of the Laplacian matrix. Moreover, the variances of the treatment effects are estimated in analogy to electrical effective resistances. It is shown that this method, being computationally simple, leads to the usual fixed effect model estimate when applied to pairwise meta-analysis and is consistent with published results when applied to network meta-analysis examples from the literature. Moreover, problems of heterogeneity and inconsistency, random effects modeling and including multi-armed trials are addressed. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Statistical methodology for estimating the mean difference in a meta-analysis without study-specific variance information.

PubMed

Sangnawakij, Patarawan; Böhning, Dankmar; Adams, Stephen; Stanton, Michael; Holling, Heinz

2017-04-30

Statistical inference for analyzing the results from several independent studies on the same quantity of interest has been investigated frequently in recent decades. Typically, any meta-analytic inference requires that the quantity of interest is available from each study together with an estimate of its variability. The current work is motivated by a meta-analysis on comparing two treatments (thoracoscopic and open) of congenital lung malformations in young children. Quantities of interest include continuous end-points such as length of operation or number of chest tube days. As studies only report mean values (and no standard errors or confidence intervals), the question arises how meta-analytic inference can be developed. We suggest two methods to estimate study-specific variances in such a meta-analysis, where only sample means and sample sizes are available in the treatment arms. A general likelihood ratio test is derived for testing equality of variances in two groups. By means of simulation studies, the bias and estimated standard error of the overall mean difference from both methodologies are evaluated and compared with two existing approaches: complete study analysis only and partial variance information. The performance of the test is evaluated in terms of type I error. Additionally, we illustrate these methods in the meta-analysis on comparing thoracoscopic and open surgery for congenital lung malformations and in a meta-analysis on the change in renal function after kidney donation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis

PubMed Central

Kang, Sang Wook; Kim, Su Kang; Jung, Hee-Jae; Kim, Kwan-Il; Kim, Jinju

2016-01-01

The relationship between polymorphism of the angiotensin I converting enzyme (ACE) gene and chronic obstructive pulmonary disease (COPD) has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p > 0.05 in each model). In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population (codominant 2, OR = 3.126, 95% CI = 1.919–5.093, p < 0.001; recessive, OR = 3.326, 95% CI = 2.190–5.050, p < 0.001) but not in the Caucasian population (p > 0.05 in each model). In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample. PMID:27830153

Detecting and correcting for publication bias in meta-analysis - A truncated normal distribution approach.

PubMed

Zhu, Qiaohao; Carriere, K C

2016-01-01

Publication bias can significantly limit the validity of meta-analysis when trying to draw conclusion about a research question from independent studies. Most research on detection and correction for publication bias in meta-analysis focus mainly on funnel plot-based methodologies or selection models. In this paper, we formulate publication bias as a truncated distribution problem, and propose new parametric solutions. We develop methodologies of estimating the underlying overall effect size and the severity of publication bias. We distinguish the two major situations, in which publication bias may be induced by: (1) small effect size or (2) large p-value. We consider both fixed and random effects models, and derive estimators for the overall mean and the truncation proportion. These estimators will be obtained using maximum likelihood estimation and method of moments under fixed- and random-effects models, respectively. We carried out extensive simulation studies to evaluate the performance of our methodology, and to compare with the non-parametric Trim and Fill method based on funnel plot. We find that our methods based on truncated normal distribution perform consistently well, both in detecting and correcting publication bias under various situations.

Overcoming redundancies in bedside nursing assessments by validating a parsimonious meta-tool: findings from a methodological exercise study.

PubMed

Palese, Alvisa; Marini, Eva; Guarnier, Annamaria; Barelli, Paolo; Zambiasi, Paola; Allegrini, Elisabetta; Bazoli, Letizia; Casson, Paola; Marin, Meri; Padovan, Marisa; Picogna, Michele; Taddia, Patrizia; Chiari, Paolo; Salmaso, Daniele; Marognolli, Oliva; Canzan, Federica; Ambrosi, Elisa; Saiani, Luisa; Grassetti, Luca

2016-10-01

There is growing interest in validating tools aimed at supporting the clinical decision-making process and research. However, an increased bureaucratization of clinical practice and redundancies in the measures collected have been reported by clinicians. Redundancies in clinical assessments affect negatively both patients and nurses. To validate a meta-tool measuring the risks/problems currently estimated by multiple tools used in daily practice. A secondary analysis of a database was performed, using a cross-validation and a longitudinal study designs. In total, 1464 patients admitted to 12 medical units in 2012 were assessed at admission with the Brass, Barthel, Conley and Braden tools. Pertinent outcomes such as the occurrence of post-discharge need for resources and functional decline at discharge, as well as falls and pressure sores, were measured. Explorative factor analysis of each tool, inter-tool correlations and a conceptual evaluation of the redundant/similar items across tools were performed. Therefore, the validation of the meta-tool was performed through explorative factor analysis, confirmatory factor analysis and the structural equation model to establish the ability of the meta-tool to predict the outcomes estimated by the original tools. High correlations between the tools have emerged (from r 0.428 to 0.867) with a common variance from 18.3% to 75.1%. Through a conceptual evaluation and explorative factor analysis, the items were reduced from 42 to 20, and the three factors that emerged were confirmed by confirmatory factor analysis. According to the structural equation model results, two out of three emerged factors predicted the outcomes. From the initial 42 items, the meta-tool is composed of 20 items capable of predicting the outcomes as with the original tools. © 2016 John Wiley & Sons, Ltd.

Cooperative macromolecular device revealed by meta-analysis of static and time-resolved structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Zhong; Šrajer, Vukica; Knapp, James E.

2013-04-08

Here we present a meta-analysis of a large collection of static structures of a protein in the Protein Data Bank in order to extract the progression of structural events during protein function. We apply this strategy to the homodimeric hemoglobin HbI from Scapharca inaequivalvis. We derive a simple dynamic model describing how binding of the first ligand in one of the two chemically identical subunits facilitates a second binding event in the other partner subunit. The results of our ultrafast time-resolved crystallographic studies support this model. We demonstrate that HbI functions like a homodimeric mechanical device, such as pliers ormore » scissors. Ligand-induced motion originating in one subunit is transmitted to the other via conserved pivot points, where the E and F' helices from two partner subunits are 'bolted' together to form a stable dimer interface permitting slight relative rotation but preventing sliding.« less

Structural basis for regioisomerization in the alkali-metal-mediated zincation (AMMZn) of trifluoromethyl benzene by isolation of kinetic and thermodynamic intermediates.

PubMed

Armstrong, David R; Blair, Victoria L; Clegg, William; Dale, Sophie H; Garcia-Alvarez, Joaquin; Honeyman, Gordon W; Hevia, Eva; Mulvey, Robert E; Russo, Luca

2010-07-14

Performed with a desire to advance knowledge of the structures and mechanisms governing alkali-metal-mediated zincation, this study monitors the reaction between the TMP-dialkylzincate reagent [(TMEDA)Na(TMP)((t)Bu)Zn((t)Bu)] 1 and trifluoromethyl benzene C(6)H(5)CF(3) 2. A complicated mixture of products is observed at room temperature. X-ray crystallography has identified two of these products as ortho- and meta-regioisomers of heterotrianionic [(TMEDA)Na(TMP)(C(6)H(4)-CF(3))Zn((t)Bu)], 3-ortho and 3-meta, respectively. Multinuclear NMR data of the bulk crystalline product confirm the presence of these two regioisomers as well as a third isomer, 3-para, in a respective ratio of 20:11:1, and an additional product 4, which also exhibits ortho-zincation of the aryl substrate. Repeating the reaction at 0 degrees C gave exclusively 4, which was crystallographically characterized as [{(TMEDA)(2)Na}(+){Zn(C(6)H(4)-CF(3))((t)Bu)(2)}(-)]. Mimicking the original room-temperature reaction, this kinetic product was subsequently reacted with TMP(H) to afford a complicated mixture of products, including significantly the three regioisomers of 3. Surprisingly, 4 adopts a solvent-separated ion pair arrangement in contrast to the contacted ion variants of 3-ortho and 3-meta. Aided by DFT calculations on model systems, discussion focuses on the different basicities, amido or alkyl, and steps, exhibited in these reactions, and how the structures and bonding within these isolated key metallic intermediates (prior to any electrophilic interception step), specifically the interactions involving the alkali metal, influence the regioselectivity of the Zn-H exchange process.

Graphical tools for network meta-analysis in STATA.

PubMed

Chaimani, Anna; Higgins, Julian P T; Mavridis, Dimitris; Spyridonos, Panagiota; Salanti, Georgia

2013-01-01

Network meta-analysis synthesizes direct and indirect evidence in a network of trials that compare multiple interventions and has the potential to rank the competing treatments according to the studied outcome. Despite its usefulness network meta-analysis is often criticized for its complexity and for being accessible only to researchers with strong statistical and computational skills. The evaluation of the underlying model assumptions, the statistical technicalities and presentation of the results in a concise and understandable way are all challenging aspects in the network meta-analysis methodology. In this paper we aim to make the methodology accessible to non-statisticians by presenting and explaining a series of graphical tools via worked examples. To this end, we provide a set of STATA routines that can be easily employed to present the evidence base, evaluate the assumptions, fit the network meta-analysis model and interpret its results.

Graphical Tools for Network Meta-Analysis in STATA

PubMed Central

Chaimani, Anna; Higgins, Julian P. T.; Mavridis, Dimitris; Spyridonos, Panagiota; Salanti, Georgia

2013-01-01

Network meta-analysis synthesizes direct and indirect evidence in a network of trials that compare multiple interventions and has the potential to rank the competing treatments according to the studied outcome. Despite its usefulness network meta-analysis is often criticized for its complexity and for being accessible only to researchers with strong statistical and computational skills. The evaluation of the underlying model assumptions, the statistical technicalities and presentation of the results in a concise and understandable way are all challenging aspects in the network meta-analysis methodology. In this paper we aim to make the methodology accessible to non-statisticians by presenting and explaining a series of graphical tools via worked examples. To this end, we provide a set of STATA routines that can be easily employed to present the evidence base, evaluate the assumptions, fit the network meta-analysis model and interpret its results. PMID:24098547

Mobile Phone Apps to Promote Weight Loss and Increase Physical Activity: A Systematic Review and Meta-Analysis.

PubMed

Flores Mateo, Gemma; Granado-Font, Esther; Ferré-Grau, Carme; Montaña-Carreras, Xavier

2015-11-10

To our knowledge, no meta-analysis to date has assessed the efficacy of mobile phone apps to promote weight loss and increase physical activity. To perform a systematic review and meta-analysis of studies to compare the efficacy of mobile phone apps compared with other approaches to promote weight loss and increase physical activity. We conducted a systematic review and meta-analysis of relevant studies identified by a search of PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus from their inception through to August 2015. Two members of the study team (EG-F, GF-M) independently screened studies for inclusion criteria and extracted data. We included all controlled studies that assessed a mobile phone app intervention with weight-related health measures (ie, body weight, body mass index, or waist circumference) or physical activity outcomes. Net change estimates comparing the intervention group with the control group were pooled across studies using random-effects models. We included 12 articles in this systematic review and meta-analysis. Compared with the control group, use of a mobile phone app was associated with significant changes in body weight (kg) and body mass index (kg/m(2)) of -1.04 kg (95% CI -1.75 to -0.34; I2 = 41%) and -0.43 kg/m(2) (95% CI -0.74 to -0.13; I2 = 50%), respectively. Moreover, a nonsignificant difference in physical activity was observed between the two groups (standardized mean difference 0.40, 95% CI -0.07 to 0.87; I2 = 93%). These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. Evidence from this study shows that mobile phone app-based interventions may be useful tools for weight loss.

Statistical Power in Meta-Analysis

ERIC Educational Resources Information Center

Liu, Jin

2015-01-01

Statistical power is important in a meta-analysis study, although few studies have examined the performance of simulated power in meta-analysis. The purpose of this study is to inform researchers about statistical power estimation on two sample mean difference test under different situations: (1) the discrepancy between the analytical power and…

Clinical information modeling processes for semantic interoperability of electronic health records: systematic review and inductive analysis.

PubMed

Moreno-Conde, Alberto; Moner, David; Cruz, Wellington Dimas da; Santos, Marcelo R; Maldonado, José Alberto; Robles, Montserrat; Kalra, Dipak

2015-07-01

This systematic review aims to identify and compare the existing processes and methodologies that have been published in the literature for defining clinical information models (CIMs) that support the semantic interoperability of electronic health record (EHR) systems. Following the preferred reporting items for systematic reviews and meta-analyses systematic review methodology, the authors reviewed published papers between 2000 and 2013 that covered that semantic interoperability of EHRs, found by searching the PubMed, IEEE Xplore, and ScienceDirect databases. Additionally, after selection of a final group of articles, an inductive content analysis was done to summarize the steps and methodologies followed in order to build CIMs described in those articles. Three hundred and seventy-eight articles were screened and thirty six were selected for full review. The articles selected for full review were analyzed to extract relevant information for the analysis and characterized according to the steps the authors had followed for clinical information modeling. Most of the reviewed papers lack a detailed description of the modeling methodologies used to create CIMs. A representative example is the lack of description related to the definition of terminology bindings and the publication of the generated models. However, this systematic review confirms that most clinical information modeling activities follow very similar steps for the definition of CIMs. Having a robust and shared methodology could improve their correctness, reliability, and quality. Independently of implementation technologies and standards, it is possible to find common patterns in methods for developing CIMs, suggesting the viability of defining a unified good practice methodology to be used by any clinical information modeler. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A process for assessing the feasibility of a network meta-analysis: a case study of everolimus in combination with hormonal therapy versus chemotherapy for advanced breast cancer.

PubMed

Cope, Shannon; Zhang, Jie; Saletan, Stephen; Smiechowski, Brielan; Jansen, Jeroen P; Schmid, Peter

2014-06-05

The aim of this study is to outline a general process for assessing the feasibility of performing a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative treatments for a specific disease population. Several steps to assess the feasibility of an NMA are proposed based on existing recommendations. Next, a case study is used to illustrate this NMA feasibility assessment process in order to compare everolimus in combination with hormonal therapy to alternative chemotherapies in terms of progression-free survival for women with advanced breast cancer. A general process for assessing the feasibility of an NMA is outlined that incorporates explicit steps to visualize the heterogeneity in terms of treatment and outcome characteristics (Part A) as well as the study and patient characteristics (Part B). Additionally, steps are performed to illustrate differences within and across different types of direct comparisons in terms of baseline risk (Part C) and observed treatment effects (Part D) since there is a risk that the treatment effect modifiers identified may not explain the observed heterogeneity or inconsistency in the results due to unexpected, unreported or unmeasured differences. Depending on the data available, alternative approaches are suggested: list assumptions, perform a meta-regression analysis, subgroup analysis, sensitivity analyses, or summarize why an NMA is not feasible. The process outlined to assess the feasibility of an NMA provides a stepwise framework that will help to ensure that the underlying assumptions are systematically explored and that the risks (and benefits) of pooling and indirectly comparing treatment effects from RCTs for a particular research question are transparent.

Associations between CD24 gene polymorphisms and inflammatory bowel disease: A meta-analysis.

PubMed

Huang, Xiao-Li; Xu, Dong-Hua; Wang, Guo-Pin; Zhang, Shu; Yu, Cheng-Gong

2015-05-21

To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). The PubMed, Web of Science and Cochrane Library databases were searched (up to May 30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis", "IBD", "CD" or "UC"; and "polymorphism", "mutation" or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed. Stata SE12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T (rs8734) and TG1527del (rs3838646), in the CD24 gene were assessed. A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD (all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170T polymorphism was associated with an increased risk of UC in a dominant model (OR = 1.79, 95%CI: 1.15-2.77, P = 0.009) and an additive model (OR = 1.87, 95%CI: 1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570del polymorphism was significantly associated with CD in the additive model (OR = 1.24, 95%CI: 1.01-1.52, P = 0.037). Our findings provide evidence that the CD24 C170T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527del polymorphism might be associated with the risk of CD.

Effectiveness of en masse versus two-step retraction: a systematic review and meta-analysis.

PubMed

Rizk, Mumen Z; Mohammed, Hisham; Ismael, Omar; Bearn, David R

2018-01-05

This review aims to compare the effectiveness of en masse and two-step retraction methods during orthodontic space closure regarding anchorage preservation and anterior segment retraction and to assess their effect on the duration of treatment and root resorption. An electronic search for potentially eligible randomized controlled trials and prospective controlled trials was performed in five electronic databases up to July 2017. The process of study selection, data extraction, and quality assessment was performed by two reviewers independently. A narrative review is presented in addition to a quantitative synthesis of the pooled results where possible. The Cochrane risk of bias tool and the Newcastle-Ottawa Scale were used for the methodological quality assessment of the included studies. Eight studies were included in the qualitative synthesis in this review. Four studies were included in the quantitative synthesis. En masse/miniscrew combination showed a statistically significant standard mean difference regarding anchorage preservation - 2.55 mm (95% CI - 2.99 to - 2.11) and the amount of upper incisor retraction - 0.38 mm (95% CI - 0.70 to - 0.06) when compared to a two-step/conventional anchorage combination. Qualitative synthesis suggested that en masse retraction requires less time than two-step retraction with no difference in the amount of root resorption. Both en masse and two-step retraction methods are effective during the space closure phase. The en masse/miniscrew combination is superior to the two-step/conventional anchorage combination with regard to anchorage preservation and amount of retraction. Limited evidence suggests that anchorage reinforcement with a headgear produces similar results with both retraction methods. Limited evidence also suggests that en masse retraction may require less time and that no significant differences exist in the amount of root resorption between the two methods.

Get Real in Individual Participant Data (IPD) Meta-Analysis: A Review of the Methodology

ERIC Educational Resources Information Center

Debray, Thomas P. A.; Moons, Karel G. M.; van Valkenhoef, Gert; Efthimiou, Orestis; Hummel, Noemi; Groenwold, Rolf H. H.; Reitsma, Johannes B.

2015-01-01

Individual participant data (IPD) meta-analysis is an increasingly used approach for synthesizing and investigating treatment effect estimates. Over the past few years, numerous methods for conducting an IPD meta-analysis (IPD-MA) have been proposed, often making different assumptions and modeling choices while addressing a similar research…

Child-Centered Play Therapy in the Schools: Review and Meta-Analysis

ERIC Educational Resources Information Center

Ray, Dee C.; Armstrong, Stephen A.; Balkin, Richard S.; Jayne, Kimberly M.

2015-01-01

The authors conducted a meta-analysis and systematic review that examined 23 studies evaluating the effectiveness of child centered play therapy (CCPT) conducted in elementary schools. Meta-analysis results were explored using a random effects model for mean difference and mean gain effect size estimates. Results revealed statistically significant…

Hemihepatic versus total hepatic inflow occlusion during hepatectomy: a systematic review and meta-analysis.

PubMed

Wang, Hai-Qing; Yang, Jia-Yin; Yan, Lu-Nan

2011-07-14

To evaluate the clinical outcomes of patients undergoing hepatectomy with hemihepatic vascular occlusion (HHO) compared with total hepatic inflow occlusion (THO). Randomized controlled trials (RCTs) comparing hemihepatic vascular occlusion and total hepatic inflow occlusion were included by a systematic literature search. Two authors independently assessed the trials for inclusion and extracted the data. A meta-analysis was conducted to estimate blood loss, transfusion requirement, and liver injury based on the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Either the fixed effects model or random effects model was used. Four RCTs including 338 patients met the predefined inclusion criteria. A total of 167 patients were treated with THO and 171 with HHO. Meta-analysis of AST levels on postoperative day 1 indicated higher levels in the THO group with weighted mean difference (WMD) 342.27; 95% confidence intervals (CI) 217.28-467.26; P = 0.00 001; I(2) = 16%. Meta-analysis showed no significant difference between THO group and HHO group on blood loss, transfusion requirement, mortality, morbidity, operating time, ischemic duration, hospital stay, ALT levels on postoperative day 1, 3 and 7 and AST levels on postoperative day 3 and 7. Hemihepatic vascular occlusion does not offer satisfying benefit to the patients undergoing hepatic resection. However, they have less liver injury after liver resections.

Hemihepatic versus total hepatic inflow occlusion during hepatectomy: A systematic review and meta-analysis

PubMed Central

Wang, Hai-Qing; Yang, Jia-Yin; Yan, Lu-Nan

2011-01-01

AIM: To evaluate the clinical outcomes of patients undergoing hepatectomy with hemihepatic vascular occlusion (HHO) compared with total hepatic inflow occlusion (THO). METHODS: Randomized controlled trials (RCTs) comparing hemihepatic vascular occlusion and total hepatic inflow occlusion were included by a systematic literature search. Two authors independently assessed the trials for inclusion and extracted the data. A meta-analysis was conducted to estimate blood loss, transfusion requirement, and liver injury based on the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Either the fixed effects model or random effects model was used. RESULTS: Four RCTs including 338 patients met the predefined inclusion criteria. A total of 167 patients were treated with THO and 171 with HHO. Meta-analysis of AST levels on postoperative day 1 indicated higher levels in the THO group with weighted mean difference (WMD) 342.27; 95% confidence intervals (CI) 217.28-467.26; P = 0.00 001; I2 = 16%. Meta-analysis showed no significant difference between THO group and HHO group on blood loss, transfusion requirement, mortality, morbidity, operating time, ischemic duration, hospital stay, ALT levels on postoperative day 1, 3 and 7 and AST levels on postoperative day 3 and 7. CONCLUSION: Hemihepatic vascular occlusion does not offer satisfying benefit to the patients undergoing hepatic resection. However, they have less liver injury after liver resections. PMID:21912460

Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers

PubMed Central

Chang, Ellen T.; Delzell, Elizabeth

2016-01-01

ABSTRACT This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0–1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0–1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7–1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6–1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding may account for observed associations. Meta-analysis is constrained by few studies and a crude exposure metric, while the overall body of literature is methodologically limited and findings are not strong or consistent. Thus, a causal relationship has not been established between glyphosate exposure and risk of any type of LHC. PMID:27015139

Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers.

PubMed

Chang, Ellen T; Delzell, Elizabeth

2016-01-01

This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0-1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0-1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7-1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6-1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding may account for observed associations. Meta-analysis is constrained by few studies and a crude exposure metric, while the overall body of literature is methodologically limited and findings are not strong or consistent. Thus, a causal relationship has not been established between glyphosate exposure and risk of any type of LHC.

Meta-Analysis of the Effect of Chest Shielding on Preventing Patent Ductus Arteriosus in Premature Infants.

PubMed

Mannan, Javed; Amin, Sanjiv B

2017-03-01

Objective  This study aims to perform a meta-analysis of randomized studies to evaluate if chest shielding during phototherapy is associated with decreased incidence of patent ductus arteriosus (PDA) in premature infants. Design/Methods  We used published guidelines for the meta-analysis of clinical trials. The search strategy included electronic searches of CINAHL, CENTRAL Cochrane Library, MEDLINE, PubMed, and abstracts presented at the Pediatric Academic Societies. Inclusion criteria were randomized controlled trials (RCTs), quasi-RCTs or cluster RCTs published in English and involving chest shielding during phototherapy in premature infants with PDA as an outcome. Exclusion criteria involved case reports, case series, and multiple publications from the same author. Heterogeneity testing using Q statistics was performed to evaluate the variance between studies. Results  Two RCTs met study criteria. There was heterogeneity (I 2 : 55.4%) between the two trials. Meta-analysis of RCTs using the random effect model demonstrated that chest shielding during phototherapy was associated with decreased incidence of PDA (odds ratio: 0.47, 95% confidence interval: 0.23-0.96). There was no publication bias on Eggers test. Heterogeneity was seen in gestational age, gender, prophylactic use of postnatal indomethacin, duration of phototherapy, and assessment of PDA. Conclusion  Chest shielding during phototherapy may be associated with decreased incidence of PDA among premature infants. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Investigation of 2-stage meta-analysis methods for joint longitudinal and time-to-event data through simulation and real data application.

PubMed

Sudell, Maria; Tudur Smith, Catrin; Gueyffier, François; Kolamunnage-Dona, Ruwanthi

2018-04-15

Joint modelling of longitudinal and time-to-event data is often preferred over separate longitudinal or time-to-event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time-to-event outcomes. The joint modelling literature focuses mainly on the analysis of single studies with no methods currently available for the meta-analysis of joint model estimates from multiple studies. We propose a 2-stage method for meta-analysis of joint model estimates. These methods are applied to the INDANA dataset to combine joint model estimates of systolic blood pressure with time to death, time to myocardial infarction, and time to stroke. Results are compared to meta-analyses of separate longitudinal or time-to-event models. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. Using the real dataset, similar results were obtained by using the separate and joint analyses. However, the simulation study indicated a benefit of use of joint rather than separate methods in a meta-analytic setting where association exists between the longitudinal and time-to-event outcomes. Where evidence of association between longitudinal and time-to-event outcomes exists, results from joint models over standalone analyses should be pooled in 2-stage meta-analyses. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Predicting Pilot Performance in Off-Nominal Conditions: A Meta-Analysis and Model Validation

NASA Technical Reports Server (NTRS)

Wickens, C.D.; Hooey, B.L.; Gore, B.F.; Sebok, A.; Koenecke, C.; Salud, E.

2009-01-01

Pilot response to off-nominal (very rare) events represents a critical component to understanding the safety of next generation airspace technology and procedures. We describe a meta-analysis designed to integrate the existing data regarding pilot accuracy of detecting rare, unexpected events such as runway incursions in realistic flight simulations. Thirty-five studies were identified and pilot responses were categorized by expectancy, event location, and whether the pilot was flying with a highway-in-the-sky display. All three dichotomies produced large, significant effects on event miss rate. A model of human attention and noticing, N-SEEV, was then used to predict event noticing performance as a function of event salience and expectancy, and retinal eccentricity. Eccentricity is predicted from steady state scanning by the SEEV model of attention allocation. The model was used to predict miss rates for the expectancy, location and highway-in-the-sky (HITS) effects identified in the meta-analysis. The correlation between model-predicted results and data from the meta-analysis was 0.72.

Dynamic sensitivity analysis of long running landslide models through basis set expansion and meta-modelling

NASA Astrophysics Data System (ADS)

Rohmer, Jeremy

2016-04-01

Predicting the temporal evolution of landslides is typically supported by numerical modelling. Dynamic sensitivity analysis aims at assessing the influence of the landslide properties on the time-dependent predictions (e.g., time series of landslide displacements). Yet two major difficulties arise: 1. Global sensitivity analysis require running the landslide model a high number of times (> 1000), which may become impracticable when the landslide model has a high computation time cost (> several hours); 2. Landslide model outputs are not scalar, but function of time, i.e. they are n-dimensional vectors with n usually ranging from 100 to 1000. In this article, I explore the use of a basis set expansion, such as principal component analysis, to reduce the output dimensionality to a few components, each of them being interpreted as a dominant mode of variation in the overall structure of the temporal evolution. The computationally intensive calculation of the Sobol' indices for each of these components are then achieved through meta-modelling, i.e. by replacing the landslide model by a "costless-to-evaluate" approximation (e.g., a projection pursuit regression model). The methodology combining "basis set expansion - meta-model - Sobol' indices" is then applied to the La Frasse landslide to investigate the dynamic sensitivity analysis of the surface horizontal displacements to the slip surface properties during the pore pressure changes. I show how to extract information on the sensitivity of each main modes of temporal behaviour using a limited number (a few tens) of long running simulations. In particular, I identify the parameters, which trigger the occurrence of a turning point marking a shift between a regime of low values of landslide displacements and one of high values.

A Bayesian Nonparametric Meta-Analysis Model

ERIC Educational Resources Information Center

Karabatsos, George; Talbott, Elizabeth; Walker, Stephen G.

2015-01-01

In a meta-analysis, it is important to specify a model that adequately describes the effect-size distribution of the underlying population of studies. The conventional normal fixed-effect and normal random-effects models assume a normal effect-size population distribution, conditionally on parameters and covariates. For estimating the mean overall…

A Noncentral "t" Regression Model for Meta-Analysis

ERIC Educational Resources Information Center

Camilli, Gregory; de la Torre, Jimmy; Chiu, Chia-Yi

2010-01-01

In this article, three multilevel models for meta-analysis are examined. Hedges and Olkin suggested that effect sizes follow a noncentral "t" distribution and proposed several approximate methods. Raudenbush and Bryk further refined this model; however, this procedure is based on a normal approximation. In the current research literature, this…

Modeling Woven Polymer Matrix Composites with MAC/GMC

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steven M. (Technical Monitor)

2000-01-01

NASA's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) is used to predict the elastic properties of plain weave polymer matrix composites (PMCs). The traditional one step three-dimensional homogertization procedure that has been used in conjunction with MAC/GMC for modeling woven composites in the past is inaccurate due to the lack of shear coupling inherent to the model. However, by performing a two step homogenization procedure in which the woven composite repeating unit cell is homogenized independently in the through-thickness direction prior to homogenization in the plane of the weave, MAC/GMC can now accurately model woven PMCs. This two step procedure is outlined and implemented, and predictions are compared with results from the traditional one step approach and other models and experiments from the literature. Full coupling of this two step technique with MAC/ GMC will result in a widely applicable, efficient, and accurate tool for the design and analysis of woven composite materials and structures.

Meta-markers for the differential diagnosis of lung cancer and lung disease.

PubMed

Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

2016-10-04

Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Two-step sensitivity testing of parametrized and regionalized life cycle assessments: methodology and case study.

PubMed

Mutel, Christopher L; de Baan, Laura; Hellweg, Stefanie

2013-06-04

Comprehensive sensitivity analysis is a significant tool to interpret and improve life cycle assessment (LCA) models, but is rarely performed. Sensitivity analysis will increase in importance as inventory databases become regionalized, increasing the number of system parameters, and parametrized, adding complexity through variables and nonlinear formulas. We propose and implement a new two-step approach to sensitivity analysis. First, we identify parameters with high global sensitivities for further examination and analysis with a screening step, the method of elementary effects. Second, the more computationally intensive contribution to variance test is used to quantify the relative importance of these parameters. The two-step sensitivity test is illustrated on a regionalized, nonlinear case study of the biodiversity impacts from land use of cocoa production, including a worldwide cocoa products trade model. Our simplified trade model can be used for transformable commodities where one is assessing market shares that vary over time. In the case study, the highly uncertain characterization factors for the Ivory Coast and Ghana contributed more than 50% of variance for almost all countries and years examined. The two-step sensitivity test allows for the interpretation, understanding, and improvement of large, complex, and nonlinear LCA systems.

A brain-region-based meta-analysis method utilizing the Apriori algorithm.

PubMed

Niu, Zhendong; Nie, Yaoxin; Zhou, Qian; Zhu, Linlin; Wei, Jieyao

2016-05-18

Brain network connectivity modeling is a crucial method for studying the brain's cognitive functions. Meta-analyses can unearth reliable results from individual studies. Meta-analytic connectivity modeling is a connectivity analysis method based on regions of interest (ROIs) which showed that meta-analyses could be used to discover brain network connectivity. In this paper, we propose a new meta-analysis method that can be used to find network connectivity models based on the Apriori algorithm, which has the potential to derive brain network connectivity models from activation information in the literature, without requiring ROIs. This method first extracts activation information from experimental studies that use cognitive tasks of the same category, and then maps the activation information to corresponding brain areas by using the automatic anatomical label atlas, after which the activation rate of these brain areas is calculated. Finally, using these brain areas, a potential brain network connectivity model is calculated based on the Apriori algorithm. The present study used this method to conduct a mining analysis on the citations in a language review article by Price (Neuroimage 62(2):816-847, 2012). The results showed that the obtained network connectivity model was consistent with that reported by Price. The proposed method is helpful to find brain network connectivity by mining the co-activation relationships among brain regions. Furthermore, results of the co-activation relationship analysis can be used as a priori knowledge for the corresponding dynamic causal modeling analysis, possibly achieving a significant dimension-reducing effect, thus increasing the efficiency of the dynamic causal modeling analysis.

Alcohol Intake and Risk of Thyroid Cancer: A Meta-Analysis of Observational Studies.

PubMed

Hong, Seung-Hee; Myung, Seung-Kwon; Kim, Hyeon Suk

2017-04-01

The purpose of this study was to assess whether alcohol intake is associated with the risk of thyroid cancer by a meta-analysis of observational studies. We searched PubMed and EMBASE in June of 2015 to locate eligible studies. We included observational studies such as cross-sectional studies, case-control studies, and cohort studies reporting odd ratios (ORs) or relative risk (RRs) with 95% confidence intervals (CIs). We included 33 observational studies with two cross-sectional studies, 20 case-controls studies, and 11 cohort studies, which involved a total of 7,725 thyroid cancer patients and 3,113,679 participants without thyroid cancer in the final analysis. In the fixed-effect model meta-analysis of all 33 studies, we found that alcohol intake was consistently associated with a decreased risk of thyroid cancer (OR or RR, 0.74; 95% CI, 0.67 to 0.83; I 2 =38.6%). In the subgroup meta-analysis by type of study, alcohol intake also decreased the risk of thyroid cancer in both case-control studies (OR, 0.77; 95% CI, 0.65 to 0.92; I 2 =29.5%; n=20) and cohort studies (RR, 0.70; 95% CI, 0.60 to 0.82; I 2 =0%; n=11). Moreover, subgroup meta-analyses by type of thyroid cancer, gender, amount of alcohol consumed, and methodological quality of study showed that alcohol intake was significantly associated with a decreased risk of thyroid cancer. The current meta-analysis of observational studies found that, unlike most of other types of cancer, alcohol intake decreased the risk of thyroid cancer.

Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

PubMed

Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

2016-03-01

Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P < 0.00001). Meta-analysis of two studies with adjusted risk estimates showed that hyperuricemia was independently associated with increased risk of peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

Advances in the meta-analysis of heterogeneous clinical trials I: The inverse variance heterogeneity model.

PubMed

Doi, Suhail A R; Barendregt, Jan J; Khan, Shahjahan; Thalib, Lukman; Williams, Gail M

2015-11-01

This article examines an improved alternative to the random effects (RE) model for meta-analysis of heterogeneous studies. It is shown that the known issues of underestimation of the statistical error and spuriously overconfident estimates with the RE model can be resolved by the use of an estimator under the fixed effect model assumption with a quasi-likelihood based variance structure - the IVhet model. Extensive simulations confirm that this estimator retains a correct coverage probability and a lower observed variance than the RE model estimator, regardless of heterogeneity. When the proposed IVhet method is applied to the controversial meta-analysis of intravenous magnesium for the prevention of mortality after myocardial infarction, the pooled OR is 1.01 (95% CI 0.71-1.46) which not only favors the larger studies but also indicates more uncertainty around the point estimate. In comparison, under the RE model the pooled OR is 0.71 (95% CI 0.57-0.89) which, given the simulation results, reflects underestimation of the statistical error. Given the compelling evidence generated, we recommend that the IVhet model replace both the FE and RE models. To facilitate this, it has been implemented into free meta-analysis software called MetaXL which can be downloaded from www.epigear.com. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparing Active Pediatric Obesity Treatments Using Meta-Analysis

ERIC Educational Resources Information Center

Gilles, Allyson; Cassano, Michael; Shepherd, Elizabeth J.; Higgins, Diana; Hecker, Jeffrey E.; Nangle, Douglas W.

2008-01-01

The current meta-analysis reviews research on the treatment of pediatric obesity focusing on studies that have been published since 1994. Eleven studies (22 comparisons, 115 effect sizes, N = 447) were included in the present meta-analysis. Results indicated that comprehensive behavioral interventions may be improved in at least two ways:…

A meta-analysis of the effect of angiotensin receptor blockers and calcium channel blockers on blood pressure, glycemia and the HOMA-IR index in non-diabetic patients.

PubMed

Yang, Yue; Wei, Ri-bao; Xing, Yue; Tang, Lu; Zheng, Xiao-yong; Wang, Zi-cheng; Gao, Yu-wei; Li, Min-xia; Chen, Xiang-mei

2013-12-01

This study compared the efficacy of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) in the effect of insulin resistance (IR) as assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) in non-diabetic patients. The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify studies published before December 2012 that investigated the use of ARBs and CCBs to determine the effect on the HOMA-IR index in non-diabetics. Parameters on IR and blood pressure were collected. Review Manager 5.2 and Stata 12.0 were used to perform the meta-analysis. Fixed and random effects models were applied to various aspects of the meta-analysis, which assessed the therapeutic effects of the two types of drug using the HOMA-IR index in non-diabetic patients. The meta-analysis included five clinical trials. Patient comparisons before and after treatment with ARBs and CCBs revealed that ARBs reduced the HOMA-IR index (weighted mean difference (WMD) -0.65, 95% confidence interval (CI) -0.93 to -0.38) and fasting plasma insulin (FPI) (WMD -2.01, 95% CI -3.27 to -0.74) significantly more than CCBs. No significant differences in the therapeutic effects of these two types of drug on blood pressure were observed. Given that there are no significant differences in the therapeutic effects of ARBs and CCBs on blood pressure, as ARBs are superior to CCBs in their effect on the HOMA-IR index in non-diabetics, they might be a better choice in hypertension patients without diabetes. © 2013.

The Viral Hypothesis of Mesial Temporal Lobe Epilepsy - Is Human Herpes Virus-6 the Missing Link? A systematic review and meta-analysis.

PubMed

Wipfler, P; Dunn, N; Beiki, O; Trinka, E; Fogdell-Hahn, A

2018-01-01

Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder. Although likely multifactorial, the mechanisms underlying the etiology and pathogenesis of the disease remains unknown in majority of patients. Viruses, particularly Human Herpes Virus 6A and B (HHV-6), two neurotropic herpes viruses, have been implicated in MTLE due to their ubiquitous nature and ability to establish lifelong latency with risk of reactivation. However, the results of studies investigating this relationship are conflicting. This systematic review and meta-analysis was conducted to determine the relationship between HHV-6 DNA (not specifying if A or B) in brain tissue and MTLE based on the current evidence. Two independent assessors carried out a comprehensive electronic search to identify all relevant studies. Both fixed- and random-effects models were used to determine the overall odds ratio. A total of 10 studies met the inclusion criteria for the systematic review and eight for the meta-analysis. In 19.6% of all MTLE patients HHV-6 DNA was detected in brain tissue compared to 10.3% of all controls (p >0.05). The pooled odds ratio of HHV-6 positive cases in MTLE patients was 2.016 [95%-CI: 1.16-3.50] in the fixed effect model. The results of this meta-analysis indicate an association between HHV-6 DNA and MTLE surgically resected tissue samples, unspecified if A or B or both. However, the casual relationship and possible pathological role of HHV-6 in MTLE are yet to be elucidated. This study's results provide a basis for future studies continuing the investigation into pathological implications of HHV-6. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Molecular polygamy: The promiscuity of l-phenylalanyl-tRNA-synthetase triggers misincorporation of meta- and ortho-tyrosine in monoclonal antibodies expressed by Chinese hamster ovary cells.

PubMed

Popp, Oliver; Larraillet, Vincent; Kettenberger, Hubert; Gorr, Ingo H; Hilger, Maximiliane; Lipsmeier, Florian; Zeck, Anne; Beaucamp, Nicola

2015-06-01

In-depth analytical characterization of biotherapeutics originating from different production batches is mandatory to ensure product safety and consistent molecule efficacy. Previously, we have shown unintended incorporation of tyrosine (Tyr) and leucine/isoleucine (Leu/Ile) at phenylalanine (Phe) positions in a recombinant produced monoclonal antibody (mAb) using an orthogonal MASCOT/SIEVE based approach for mass spectrometry data analysis. The misincorporation could be avoided by sufficient supply of phenylalanine throughout the process. Several non-annotated signals in the primarily chromatographic peptide separation step for apparently single Phe→Tyr sequence variants (SVs) suggest a role for isobar tyrosine isoforms. Meta- and ortho-Tyr are spontaneously generated during aerobic fed-batch production processes using Chinese hamster ovary (CHO) cell lines. Process induced meta- and ortho-Tyr but not proteinogenic para-Tyr are incorporated at Phe locations in Phe-starved CHO cultures expressing a recombinant mAb. Furthermore, meta- and ortho-Tyr are preferably misincorporated over Leu. Structural modeling of the l-phenylalanyl-tRNA-synthetase (PheRS) substrate activation site indicates a possible fit of non-cognate ortho-Tyr and meta-Tyr substrates. Dose-dependent misincorporations of Tyr isoforms support the hypothesis that meta- and ortho-Tyr are competing, alternative substrates for PheRS in CHO processes. Finally, easily accessible at-line surrogate markers for Phe→Tyr SV formation in biotherapeutic production were defined by the calculation of critical ratios for meta-Tyr/Phe and ortho-Tyr/Phe to support early prediction of SV probability, and finally, to allow for immediate process controlled Phe→Tyr SV prevention. © 2014 Wiley Periodicals, Inc.

Metaprop: a Stata command to perform meta-analysis of binomial data.

PubMed

Nyaga, Victoria N; Arbyn, Marc; Aerts, Marc

2014-01-01

Meta-analyses have become an essential tool in synthesizing evidence on clinical and epidemiological questions derived from a multitude of similar studies assessing the particular issue. Appropriate and accessible statistical software is needed to produce the summary statistic of interest. Metaprop is a statistical program implemented to perform meta-analyses of proportions in Stata. It builds further on the existing Stata procedure metan which is typically used to pool effects (risk ratios, odds ratios, differences of risks or means) but which is also used to pool proportions. Metaprop implements procedures which are specific to binomial data and allows computation of exact binomial and score test-based confidence intervals. It provides appropriate methods for dealing with proportions close to or at the margins where the normal approximation procedures often break down, by use of the binomial distribution to model the within-study variability or by allowing Freeman-Tukey double arcsine transformation to stabilize the variances. Metaprop was applied on two published meta-analyses: 1) prevalence of HPV-infection in women with a Pap smear showing ASC-US; 2) cure rate after treatment for cervical precancer using cold coagulation. The first meta-analysis showed a pooled HPV-prevalence of 43% (95% CI: 38%-48%). In the second meta-analysis, the pooled percentage of cured women was 94% (95% CI: 86%-97%). By using metaprop, no studies with 0% or 100% proportions were excluded from the meta-analysis. Furthermore, study specific and pooled confidence intervals always were within admissible values, contrary to the original publication, where metan was used.

Political Regime and Human Capital: A Cross-Country Analysis

ERIC Educational Resources Information Center

Klomp, Jeroen; de Haan, Jakob

2013-01-01

We examine the relationship between different dimensions of the political regime in place and human capital using a two-step structural equation model. In the first step, we employ factor analysis on 16 human capital indicators to construct two new human capital measures (basic and advanced human capital). In the second step, we estimate the…

Integrative multi-platform meta-analysis of gene expression profiles in pancreatic ductal adenocarcinoma patients for identifying novel diagnostic biomarkers.

PubMed

Irigoyen, Antonio; Jimenez-Luna, Cristina; Benavides, Manuel; Caba, Octavio; Gallego, Javier; Ortuño, Francisco Manuel; Guillen-Ponce, Carmen; Rojas, Ignacio; Aranda, Enrique; Torres, Carolina; Prados, Jose

2018-01-01

Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses ('gained' genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease.

Time-dependent summary receiver operating characteristics for meta-analysis of prognostic studies.

PubMed

Hattori, Satoshi; Zhou, Xiao-Hua

2016-11-20

Prognostic studies are widely conducted to examine whether biomarkers are associated with patient's prognoses and play important roles in medical decisions. Because findings from one prognostic study may be very limited, meta-analyses may be useful to obtain sound evidence. However, prognostic studies are often analyzed by relying on a study-specific cut-off value, which can lead to difficulty in applying the standard meta-analysis techniques. In this paper, we propose two methods to estimate a time-dependent version of the summary receiver operating characteristics curve for meta-analyses of prognostic studies with a right-censored time-to-event outcome. We introduce a bivariate normal model for the pair of time-dependent sensitivity and specificity and propose a method to form inferences based on summary statistics reported in published papers. This method provides a valid inference asymptotically. In addition, we consider a bivariate binomial model. To draw inferences from this bivariate binomial model, we introduce a multiple imputation method. The multiple imputation is found to be approximately proper multiple imputation, and thus the standard Rubin's variance formula is justified from a Bayesian view point. Our simulation study and application to a real dataset revealed that both methods work well with a moderate or large number of studies and the bivariate binomial model coupled with the multiple imputation outperforms the bivariate normal model with a small number of studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The prevalence of pathological gambling among college students: a meta-analytic synthesis, 2005-2013.

PubMed

Nowak, Donald E; Aloe, Ariel M

2014-12-01

The problem of gambling addiction can be especially noteworthy among college and university students, many of whom have the resources, proximity, free time, and desire to become involved in the myriad options of gambling now available. Although limited attention has been paid specifically to college student gambling in the body of literature, there have been two published meta-analyses estimating the prevalence of probable pathological gambling among college students. This present study aims to be the third, presenting an up-to-date proportion of those students exhibiting gambling pathology, and is the first to include international studies from outside the United States and Canada. The purpose of this study was to use the most up-to-date meta-analytical procedures to synthesize the rates of probable pathological gambling for college and university students worldwide. A thorough literature review and coding procedure resulted in 19 independent data estimates retrieved from 18 studies conducted between 2005 and 2013. To synthesize the studies, a random effects model for meta-analysis was applied. The estimated proportion of probable pathological gamblers among the over 13,000 college students surveyed was computed at 10.23%, considerably higher than either of the two previously published meta-analyses, and more than double the rate reported in the first meta-analysis of this type published in 1999. Implications and recommendations for future practice in dealing with college students and gambling addiction are outlined and described for both administrators and mental health professionals.

The transcription factor p53: Not a repressor, solely an activator

PubMed Central

Fischer, Martin; Steiner, Lydia; Engeland, Kurt

2014-01-01

The predominant function of the tumor suppressor p53 is transcriptional regulation. It is generally accepted that p53-dependent transcriptional activation occurs by binding to a specific recognition site in promoters of target genes. Additionally, several models for p53-dependent transcriptional repression have been postulated. Here, we evaluate these models based on a computational meta-analysis of genome-wide data. Surprisingly, several major models of p53-dependent gene regulation are implausible. Meta-analysis of large-scale data is unable to confirm reports on directly repressed p53 target genes and falsifies models of direct repression. This notion is supported by experimental re-analysis of representative genes reported as directly repressed by p53. Therefore, p53 is not a direct repressor of transcription, but solely activates its target genes. Moreover, models based on interference of p53 with activating transcription factors as well as models based on the function of ncRNAs are also not supported by the meta-analysis. As an alternative to models of direct repression, the meta-analysis leads to the conclusion that p53 represses transcription indirectly by activation of the p53-p21-DREAM/RB pathway. PMID:25486564

A Critical Meta-Analysis of Lens Model Studies in Human Judgment and Decision-Making

PubMed Central

Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W.

2013-01-01

Achieving accurate judgment (‘judgmental achievement’) is of utmost importance in daily life across multiple domains. The lens model and the lens model equation provide useful frameworks for modeling components of judgmental achievement and for creating tools to help decision makers (e.g., physicians, teachers) reach better judgments (e.g., a correct diagnosis, an accurate estimation of intelligence). Previous meta-analyses of judgment and decision-making studies have attempted to evaluate overall judgmental achievement and have provided the basis for evaluating the success of bootstrapping (i.e., replacing judges by linear models that guide decision making). However, previous meta-analyses have failed to appropriately correct for a number of study design artifacts (e.g., measurement error, dichotomization), which may have potentially biased estimations (e.g., of the variability between studies) and led to erroneous interpretations (e.g., with regards to moderator variables). In the current study we therefore conduct the first psychometric meta-analysis of judgmental achievement studies that corrects for a number of study design artifacts. We identified 31 lens model studies (N = 1,151, k = 49) that met our inclusion criteria. We evaluated overall judgmental achievement as well as whether judgmental achievement depended on decision domain (e.g., medicine, education) and/or the level of expertise (expert vs. novice). We also evaluated whether using corrected estimates affected conclusions with regards to the success of bootstrapping with psychometrically-corrected models. Further, we introduce a new psychometric trim-and-fill method to estimate the effect sizes of potentially missing studies correct psychometric meta-analyses for effects of publication bias. Comparison of the results of the psychometric meta-analysis with the results of a traditional meta-analysis (which only corrected for sampling error) indicated that artifact correction leads to a) an increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping. PMID:24391781

A critical meta-analysis of lens model studies in human judgment and decision-making.

PubMed

Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W

2013-01-01

Achieving accurate judgment ('judgmental achievement') is of utmost importance in daily life across multiple domains. The lens model and the lens model equation provide useful frameworks for modeling components of judgmental achievement and for creating tools to help decision makers (e.g., physicians, teachers) reach better judgments (e.g., a correct diagnosis, an accurate estimation of intelligence). Previous meta-analyses of judgment and decision-making studies have attempted to evaluate overall judgmental achievement and have provided the basis for evaluating the success of bootstrapping (i.e., replacing judges by linear models that guide decision making). However, previous meta-analyses have failed to appropriately correct for a number of study design artifacts (e.g., measurement error, dichotomization), which may have potentially biased estimations (e.g., of the variability between studies) and led to erroneous interpretations (e.g., with regards to moderator variables). In the current study we therefore conduct the first psychometric meta-analysis of judgmental achievement studies that corrects for a number of study design artifacts. We identified 31 lens model studies (N = 1,151, k = 49) that met our inclusion criteria. We evaluated overall judgmental achievement as well as whether judgmental achievement depended on decision domain (e.g., medicine, education) and/or the level of expertise (expert vs. novice). We also evaluated whether using corrected estimates affected conclusions with regards to the success of bootstrapping with psychometrically-corrected models. Further, we introduce a new psychometric trim-and-fill method to estimate the effect sizes of potentially missing studies correct psychometric meta-analyses for effects of publication bias. Comparison of the results of the psychometric meta-analysis with the results of a traditional meta-analysis (which only corrected for sampling error) indicated that artifact correction leads to a) an increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping.

Classifying Correlation Matrices into Relatively Homogeneous Subgroups: A Cluster Analytic Approach

ERIC Educational Resources Information Center

Cheung, Mike W.-L.; Chan, Wai

2005-01-01

Researchers are becoming interested in combining meta-analytic techniques and structural equation modeling to test theoretical models from a pool of studies. Most existing procedures are based on the assumption that all correlation matrices are homogeneous. Few studies have addressed what the next step should be when studies being analyzed are…

A hybrid Bayesian hierarchical model combining cohort and case-control studies for meta-analysis of diagnostic tests: Accounting for partial verification bias.

PubMed

Ma, Xiaoye; Chen, Yong; Cole, Stephen R; Chu, Haitao

2016-12-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities, and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. © The Author(s) 2014.

A Hybrid Bayesian Hierarchical Model Combining Cohort and Case-control Studies for Meta-analysis of Diagnostic Tests: Accounting for Partial Verification Bias

PubMed Central

Ma, Xiaoye; Chen, Yong; Cole, Stephen R.; Chu, Haitao

2014-01-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. PMID:24862512

Determinants of Linear Judgment: A Meta-Analysis of Lens Model Studies

ERIC Educational Resources Information Center

Karelaia, Natalia; Hogarth, Robin M.

2008-01-01

The mathematical representation of E. Brunswik's (1952) lens model has been used extensively to study human judgment and provides a unique opportunity to conduct a meta-analysis of studies that covers roughly 5 decades. Specifically, the authors analyzed statistics of the "lens model equation" (L. R. Tucker, 1964) associated with 249 different…

Prevalence of Enterobius vermicularis among Children in Iran: A Systematic Review and Meta-analysis.

PubMed

Moosazadeh, Mahmood; Abedi, Ghasem; Afshari, Mahdi; Mahdavi, Seif Ali; Farshidi, Fereshteh; Kheradmand, Elham

2017-04-01

Enterobius vermicularis is a parasitic disease that is common in crowded areas such as schools and kindergartens. Primary investigations of electronic evidence have reported different prevalences of E. vermicularis in Iran. Therefore, we aimed to estimate the total prevalence of this infection among Iranian children using a meta-analysis. Relevant studies were identified in national and international databases. We selected eligible papers for meta-analysis after investigating titles, abstracts, and full texts; assessing study quality; and applying inclusion/exclusion criteria. Data were extracted by two independent researchers. The results were combined using a random effects model in Stata v. 11 software. Among 19 eligible articles including 11,676 participants, the prevalences of E. vermicularis among all children, boys, and girls were 1.2%-66.1%, 2.3%-65.5%, and 1.7%-65.5%, respectively. Pooled prevalences (95% confidence interval) of E. vermicularis among all children, boys, and girls were 17.2% (12.6%-21.8%), 17.2% (12.6%-21.8%), and 16.9% (9.03%-24.8%), respectively. This meta-analysis showed that a great majority of Iranian children are infected with E. vermicularis , possibly due to poor public health.

Meta-analysis of randomized, controlled trials comparing particular doses of griseofulvin and terbinafine for the treatment of tinea capitis.

PubMed

Gupta, Aditya K; Drummond-Main, Chris

2013-01-01

Two oral antifungal agents, griseofulvin and terbinafine, have regulatory approval in the United States, but it is unknown whether one has superior overall efficacy. Genus-specific differences in efficacy are believed to exist for the two agents. It is not clear at what doses and durations of treatment these differences apply. The goals of this meta-analysis were to determine whether a statistically significant difference in efficacy exists between these agents at a given dose and duration of each in tinea capitis infections overall and to determine whether a genus-specific difference in efficacy exists for these two treatments at a given dose and duration of each. We performed a literature search for clinically and methodologically similar randomized controlled trials comparing 8 weeks of griseofulvin (6.25-12.5 mg/kg/day) to 4 weeks of terbinafine (3.125-6.25 mg/kg/day) in the treatment of tinea capitis. A meta-analysis was performed using the Mantel-Haenszel method and random effects model; results were expressed as odds ratios with 95% confidence intervals. Meta-analysis of randomized controlled trials did not show a significant difference in the overall efficacy of the two drugs at the doses specified, but specific efficacy differences were observed based on the infectious species. For tinea capitis caused by Microsporum spp., griseofulvin is superior (p = 0.04), whereas terbinafine is superior for Trichophyton spp. infection (p = 0.04). Our results support species-specific differences in treatment efficacy between griseofulvin and terbinafine and provide a clinical context in which this knowledge may be applied. © 2012 Wiley Periodicals, Inc.

Likelihood-Based Random-Effect Meta-Analysis of Binary Events.

PubMed

Amatya, Anup; Bhaumik, Dulal K; Normand, Sharon-Lise; Greenhouse, Joel; Kaizar, Eloise; Neelon, Brian; Gibbons, Robert D

2015-01-01

Meta-analysis has been used extensively for evaluation of efficacy and safety of medical interventions. Its advantages and utilities are well known. However, recent studies have raised questions about the accuracy of the commonly used moment-based meta-analytic methods in general and for rare binary outcomes in particular. The issue is further complicated for studies with heterogeneous effect sizes. Likelihood-based mixed-effects modeling provides an alternative to moment-based methods such as inverse-variance weighted fixed- and random-effects estimators. In this article, we compare and contrast different mixed-effect modeling strategies in the context of meta-analysis. Their performance in estimation and testing of overall effect and heterogeneity are evaluated when combining results from studies with a binary outcome. Models that allow heterogeneity in both baseline rate and treatment effect across studies have low type I and type II error rates, and their estimates are the least biased among the models considered.

Skin antiseptics in venous puncture site disinfection for preventing blood culture contamination: A Bayesian network meta-analysis of randomized controlled trials.

PubMed

Liu, Wenjie; Duan, Yuchen; Cui, Wenyao; Li, Li; Wang, Xia; Dai, Heling; You, Chao; Chen, Maojun

2016-07-01

To compare the efficacy of several antiseptics in decreasing the blood culture contamination rate. Network meta-analysis. Electronic searches of PubMed and Embase were conducted up to November 2015. Only randomized controlled trials or quasi-randomized controlled trials were eligible. We applied no language restriction. A comprehensive review of articles in the reference lists was also accomplished for possible relevant studies. Relevant studies evaluating efficacy of different antiseptics in venous puncture site for decreasing the blood culture contamination rate were included. The data were extracted from the included randomized controlled trials by two authors independently. The risk of bias was evaluated using Detsky scale by two authors independently. We used WinBUGS1.43 software and statistic model described by Chaimani to perform this network meta-analysis. Then graphs of statistical results of WinBUGS1.43 software were generated using 'networkplot', 'ifplot', 'netfunnel' and 'sucra' procedure by STATA13.0. Odds ratio and 95% confidence intervals were assessed for dichotomous data. A probability of p less than 0.05 was considered to be statistically significant. Compared with ordinary meta-analyses, this network meta-analysis offered hierarchies for the efficacy of different antiseptics in decreasing the blood culture contamination rate. Seven randomized controlled trials involving 34,408 blood samples were eligible for the meta-analysis. No significant difference was found in blood culture contamination rate among different antiseptics. No significant difference was found between non-alcoholic antiseptics and alcoholic antiseptics, alcoholic chlorhexidine and povidone iodine, chlorhexidine and iodine compounds, povidone iodine and iodine tincture in this aspect, respectively. Different antiseptics may not affect the blood culture contamination rate. Different intervals between the skin disinfection and the venous puncture, the different settings (emergency room, medical wards, and intensive care units) and the performance of the phlebotomy may affect the blood culture contamination rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Childhood autism spectrum disorders and exposure to nitrogen dioxide, and particulate matter air pollution: A review and meta-analysis.

PubMed

Flores-Pajot, Marie-Claire; Ofner, Marianna; Do, Minh T; Lavigne, Eric; Villeneuve, Paul J

2016-11-01

Genetic and environmental factors have been recognized to play an important role in autism. The possibility that exposure to outdoor air pollution increases the risk of autism spectrum disorder (ASD) has been an emerging area of research. Herein, we present a systematic review, and meta-analysis of published epidemiological studies that have investigated these associations. We undertook a comprehensive search strategy to identify studies that investigated outdoor air pollution and autism in children. Overall, seven cohorts and five case-control studies met our inclusion criteria for the meta-analysis. We summarized the associations between exposure to air pollution and ASD based on the following critical exposure windows: (i) first, second and third trimester of pregnancy, (ii) entire pregnancy, and (iii) postnatal period. Random effects meta-analysis modeling was undertaken to derive pooled risk estimates for these exposures across the studies. The meta-estimates for the change in ASD associated with a 10μg/m 3 increase in exposure in PM 2.5 and 10 ppb increase in NO 2 during pregnancy were 1.34 (95% CI:0.83, 2.17) and 1.05 (95% CI:0.99, 1.11), respectively. Stronger associations were observed for exposures received after birth, but these estimates were unstable as they were based on only two studies. O 3 exposure was weakly associated with ASD during the third trimester of pregnancy and during the entire pregnancy, however, these estimates were also based on only two studies. Our meta-analysis support the hypothesis that exposure to ambient air pollution is associated with an increased risk of autism. Our findings should be interpreted cautiously due to relatively small number of studies, and several studies were unable to control for other key risk factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between the BRCA2 rs144848 polymorphism and cancer susceptibility: a meta-analysis.

PubMed

Li, Qiuyan; Guan, Rongwei; Qiao, Yuandong; Liu, Chang; He, Ning; Zhang, Xuelong; Jia, Xueyuan; Sun, Haiming; Yu, Jingcui; Xu, Lidan

2017-06-13

The BRCA2 gene plays an important role in cancer carcinogenesis, and polymorphisms in this gene have been associated with cancer risk. The BRCA2 rs144848 polymorphism has been associated with several cancers, but results have been inconsistent. In the present study, a meta-analysis was performed to assess the association between the rs144848 polymorphism and cancer risk. Literature was searched from the databases of PubMed, Embase and Google Scholar before April 2016. The fixed or random effects model was used to calculate pooled odd ratios on the basis of heterogeneity. Meta-regression, sensitivity analysis, subgroup analysis and publication bias assessment were also performed using STATA 11.0 software according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009. A total of 40 relevant studies from 30 publications including 34,911 cases and 48,329 controls were included in the final meta-analysis. Among them, 22 studies focused on breast cancer, seven on ovarian cancer, five on non-Hodgkin lymphoma, and the remaining six studies examined various other cancers. The meta-analysis results showed that there were significant associations between the rs144848 polymorphism and cancer risk in all genetic models. Stratified by cancer type, the rs144848 polymorphism was associated with non-Hodgkin lymphoma. Stratified by study design, the allele model was associated with breast cancer risk in population-based studies. The meta-analysis suggests that the BRCA2 rs144848 polymorphism may play a role in cancer risk. Further well-designed studies are warranted to confirm these results.

Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in patients with thalassemia major in Iran: A meta-analysis study

PubMed Central

Azami, Milad; Sharifi, Ali; Norozi, Siros; Mansouri, Akram; Sayehmiri, Kourosh

2017-01-01

Background: This study aimed to investigate the prevalence of diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in Iranian patients with thalassemia major. Methods: The current study has been conducted based on PRISMA guideline. To obtain the documents, Persian and English scientific databases such as Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed, ScienceDirect, Cochrane, Web of Science, Springer, Wiley Online Library as well as Google Scholar were searched until December 2015. All steps of the study were conducted by two authors independently. To the high heterogeneity of the studies, the random effect model was used to combine studies. Data were analyzed using STATA Version 11.1 software. Results: Thirty-two studies involving 3959 major thalassemia patients with mean age of 16.83 years were included in the meta-analysis. The prevalence of diabetes in Iranian patients with thalassemia major was estimated as 9% (95% CI: 6.8-10.5) and estimated rate was 12.6% (95% CI: 6.1-19.1) for males and 10.8% (95% CI: 8.2-14.5) for females. The prevalence of IFG and IGT were 12.9% (95% CI: 7-18.8) and 9.6% (95% CI: 6.6-12.5) respectively. No relationship between serum ferritin and development of diabetes was noted. Conclusion: The prevalence of diabetes, IFG, and IGT in patients with thalassemia major in Iran is high and accordingly requires new management strategies and policies to minimize endocrine disorders in Iranian patients with thalassemia major. Screening of patients for the early diagnosis of endocrine disorders particularly diabetes, IFG, and IGT is recommended. PMID:28503277

Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials

PubMed Central

Messori, A; Trippoli, S; Vaiani, M; Gorini, M; Corrado, A

2000-01-01

Objectives To determine the effectiveness of ranitidine and sucralfate in the prevention of stress ulcer in critical patients and to assess if these treatments affect the risk of nosocomial pneumonia. Design Published studies retrieved through Medline and other databases. Five meta-analyses evaluated effectiveness in terms of bleeding rates (A: ranitidine v placebo; B: sucralfate v placebo) and infectious complications in terms of incidence of nosocomial pneumonia (C: ranitidine v placebo; D: sucralfate v placebo; E: ranitidine v sucralfate). Trial quality was determined with an empirical ad hoc procedure. Main outcome measures Rates of clinically important gastrointestinal bleeding and nosocomial pneumonia (compared between the two study arms and expressed with odds ratios specific for individual studies and meta-analytic summary odds ratios). Results Meta-analysis A (five studies) comprised 398 patients; meta-analysis C (three studies) comprised 311 patients; meta-analysis D (two studies) comprised 226 patients: and meta-analysis E (eight studies) comprised 1825 patients. Meta-analysis B was not carried out as the literature search selected only one clinical trial. In meta-analysis A ranitidine was found to have the same effectiveness as placebo (odds ratio of bleeding 0.72, 95% confidence interval 0.30 to 1.70, P=0.46). In placebo controlled studies (meta-analyses C and D) ranitidine and sucralfate had no influence on the incidence of nosocomial pneumonia. In comparison with sucralfate, ranitidine significantly increased the incidence of nosocomial pneumonia (meta-analysis E: 1.35, 1.07 to 1.70, P=0.012). The mean quality score in the four analyses (on a 0 to 10 scale) ranged from 5.6 in meta-analysis E to 6.6 in meta-analysis A. Conclusions Ranitidine is ineffective in the prevention of gastrointestinal bleeding in patients in intensive care and might increase the risk of pneumonia. Studies on sucralfate do not provide conclusive results. These findings are based on small numbers of patients, and firm conclusions cannot presently be proposed. PMID:11061729

A Two-Step Approach to Uncertainty Quantification of Core Simulators

DOE PAGES

Yankov, Artem; Collins, Benjamin; Klein, Markus; ...

2012-01-01

For the multiple sources of error introduced into the standard computational regime for simulating reactor cores, rigorous uncertainty analysis methods are available primarily to quantify the effects of cross section uncertainties. Two methods for propagating cross section uncertainties through core simulators are the XSUSA statistical approach and the “two-step” method. The XSUSA approach, which is based on the SUSA code package, is fundamentally a stochastic sampling method. Alternatively, the two-step method utilizes generalized perturbation theory in the first step and stochastic sampling in the second step. The consistency of these two methods in quantifying uncertainties in the multiplication factor andmore » in the core power distribution was examined in the framework of phase I-3 of the OECD Uncertainty Analysis in Modeling benchmark. With the Three Mile Island Unit 1 core as a base model for analysis, the XSUSA and two-step methods were applied with certain limitations, and the results were compared to those produced by other stochastic sampling-based codes. Based on the uncertainty analysis results, conclusions were drawn as to the method that is currently more viable for computing uncertainties in burnup and transient calculations.« less

The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis.

PubMed

Ker, Katharine; Prieto-Merino, David; Sprigg, Nikola; Mahmood, Abda; Bath, Philip; Kang Law, Zhe; Flaherty, Katie; Roberts, Ian

2017-01-01

Introduction : The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods : The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions : This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice.

Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.

PubMed

Xu, Wei-Wei; Hu, Shen-Jiang; Wu, Tao

2017-07-01

Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

The efficacy and safety of medical leech therapy for osteoarthritis of the knee: A meta-analysis of randomized controlled trials.

PubMed

Wang, Haixia; Zhang, Jing; Chen, Liyan

2018-06-01

It is controversial on whether medical leech therapy is effective in improving pain and functional outcome in patients with knee osteoarthritis (OA). Therefore, we perform a meta-analysis from randomized controlled trials (RCTs) to evaluate the efficacy and safety of medical leech therapy in patients with knee OA. The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving medical leech therapy in patients with knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 12.0. Four RCTs with 264 patients were included in this meta-analysis. The current meta-analysis showed that there were significant differences in terms of visual analogue scale (VAS) scores and WOMAC scores at 1 week, 4weeks and 7 weeks compared with control groups. However, leech therapy was associated with a significantly higher incidence of adverse events. The overall evidence quality is moderate, which means that further research is likely to significantly change confidence in the effect estimate but may change the estimate. Medical leech therapy was associated with a significantly improved outcome in pain relief and functional recovery in patients with symptomatic knee OA. However, given the inherent limitations in the included studies, this conclusion should be interpreted cautiously. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Systematic review and meta-analysis of efficacy of mesenchymal stem cells on locomotor recovery in animal models of traumatic brain injury.

PubMed

Peng, Weijun; Sun, Jing; Sheng, Chenxia; Wang, Zhe; Wang, Yang; Zhang, Chunhu; Fan, Rong

2015-03-26

The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger's tests. Twenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1-5)×10(6) was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with administration syngeneic bone marrow-derived MSCs intravenously at cell dose of 5×10(6) at 2 months after TBI, using sevofluorane as anesthetic agent. We conclude that MSCs therapy may improve locomotor recovery after TBI. However, additional well-designed and well-reported animal studies are needed to guide further clinical studies.

Relating interesting quantitative time series patterns with text events and text features

NASA Astrophysics Data System (ADS)

Wanner, Franz; Schreck, Tobias; Jentner, Wolfgang; Sharalieva, Lyubka; Keim, Daniel A.

2013-12-01

In many application areas, the key to successful data analysis is the integrated analysis of heterogeneous data. One example is the financial domain, where time-dependent and highly frequent quantitative data (e.g., trading volume and price information) and textual data (e.g., economic and political news reports) need to be considered jointly. Data analysis tools need to support an integrated analysis, which allows studying the relationships between textual news documents and quantitative properties of the stock market price series. In this paper, we describe a workflow and tool that allows a flexible formation of hypotheses about text features and their combinations, which reflect quantitative phenomena observed in stock data. To support such an analysis, we combine the analysis steps of frequent quantitative and text-oriented data using an existing a-priori method. First, based on heuristics we extract interesting intervals and patterns in large time series data. The visual analysis supports the analyst in exploring parameter combinations and their results. The identified time series patterns are then input for the second analysis step, in which all identified intervals of interest are analyzed for frequent patterns co-occurring with financial news. An a-priori method supports the discovery of such sequential temporal patterns. Then, various text features like the degree of sentence nesting, noun phrase complexity, the vocabulary richness, etc. are extracted from the news to obtain meta patterns. Meta patterns are defined by a specific combination of text features which significantly differ from the text features of the remaining news data. Our approach combines a portfolio of visualization and analysis techniques, including time-, cluster- and sequence visualization and analysis functionality. We provide two case studies, showing the effectiveness of our combined quantitative and textual analysis work flow. The workflow can also be generalized to other application domains such as data analysis of smart grids, cyber physical systems or the security of critical infrastructure, where the data consists of a combination of quantitative and textual time series data.

Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis.

PubMed

Li, Zhouna; Jin, Zhehu

2016-01-01

Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars. Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis. Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions. There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to confirm our conclusion.

A Family-Based Association Analysis and Meta-Analysis of the Reading Disabilities Candidate Gene DYX1C1

PubMed Central

Tran, C.; Gagnon, F.; Wigg, K.G.; Feng, Y.; Gomez, L.; Cate-Carter, T.D.; Kerr, E.N.; Field, L.L.; Kaplan, B.J.; Lovett, M.W.; Barr, C.L.

2017-01-01

Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the −3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the −3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and −3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between −3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (−3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the −3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs −3G/A and 1249G/T and RD. PMID:23341075

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data.

PubMed

Bax, Leon; Yu, Ly-Mee; Ikeda, Noriaki; Tsuruta, Harukazu; Moons, Karel G M

2006-10-13

Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis. We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features. The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via http://www.mix-for-meta-analysis.info or http://sourceforge.net/projects/meta-analysis.

Prevalence of Pathogens in Poultry Meat: A Meta-Analysis of European Published Surveys

PubMed Central

2018-01-01

The objective of this study was to investigate and summarize the levels of incidence of Salmonella spp., Listeria monocytogenes, Staphylococcus aureus and Campylobacter spp. in poultry meat commercialized in Europe. After systematic review, incidence data and study characteristics were extracted from 78 studies conducted in 21 European countries. Pooled prevalence values from 203 extracted observations were estimated from random-effects meta-analysis models adjusted by pathogen, poultry type, sampling stage, cold preservation type, meat cutting type and packaging status. The results suggest that S. aureus is the main pathogen detected in poultry meat (38.5%; 95% CI: 25.4–53.4), followed by Campylobacter spp. (33.3%; 95% CI: 22.3–46.4%), while L. monocytogenes and Salmonella spp. present lower prevalence (19.3%; 95% CI: 14.4–25.3% and 7.10%; 95% CI: 4.60–10.8%, respectively). Despite the differences in prevalence, all pathogens were found in chicken and other poultry meats, at both end-processing step and retail level, in packed and unpacked products and in several meat cutting types. Prevalence data on cold preservation products also revealed that chilling and freezing can reduce the proliferation of pathogens but might not be able to inactivate them. The results of this meta-analysis highlight that further risk management strategies are needed to reduce pathogen incidence in poultry meat throughout the entire food chain across Europe, in particular for S. aureus and Campylobacter spp. PMID:29751496

Association between endothelial nitric oxide synthase (ENOS) G894T polymorphism and high altitude (HA) adaptation: a meta-analysis.

PubMed

Lu, Hong-xiang; Wang, Yu-xiao; Chen, Yu; Luo, Yong-jun

2015-11-01

Highland natives adapt well to the hypoxic environment at high altitude (HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial ni- tric oxide synthase (ENOS) G894T polymorphism contributed to the physiology and pathophysiology of hu- mans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894T polymorphism and HA adaptation through analyzing the published data. We searched all relevant literature about the ENOS G894T polymorphism and HA adaptation in PubMed, Med- line, and Embase before Step 2015. A random-effects model was applied (Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups (OR = 1.85; 95% Cl, 1.47-2.33; P < 0.0001). In addition, the GG genotype was significantly associated with HA adaptation (OR = 1.99; 95% Cl, 1.54-2.57; P < 0.0001). Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.

Formalizing the definition of meta-analysis in Molecular Ecology.

PubMed

ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E

2015-08-01

Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology. © 2015 John Wiley & Sons Ltd.

Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

PubMed

Fettiplace, Michael R; McCabe, Daniel J

2017-08-01

The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I 2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

A meta-analysis of response-time tests of the sequential two-systems model of moral judgment.

PubMed

Baron, Jonathan; Gürçay, Burcu

2017-05-01

The (generalized) sequential two-system ("default interventionist") model of utilitarian moral judgment predicts that utilitarian responses often arise from a system-two correction of system-one deontological intuitions. Response-time (RT) results that seem to support this model are usually explained by the fact that low-probability responses have longer RTs. Following earlier results, we predicted response probability from each subject's tendency to make utilitarian responses (A, "Ability") and each dilemma's tendency to elicit deontological responses (D, "Difficulty"), estimated from a Rasch model. At the point where A = D, the two responses are equally likely, so probability effects cannot account for any RT differences between them. The sequential two-system model still predicts that many of the utilitarian responses made at this point will result from system-two corrections of system-one intuitions, hence should take longer. However, when A = D, RT for the two responses was the same, contradicting the sequential model. Here we report a meta-analysis of 26 data sets, which replicated the earlier results of no RT difference overall at the point where A = D. The data sets used three different kinds of moral judgment items, and the RT equality at the point where A = D held for all three. In addition, we found that RT increased with A-D. This result holds for subjects (characterized by Ability) but not for items (characterized by Difficulty). We explain the main features of this unanticipated effect, and of the main results, with a drift-diffusion model.

Effects of Deficient Reporting on Meta-Analysis: A Conceptual Framework and Reanalysis

ERIC Educational Resources Information Center

Orwin, Robert G.; Cordray, David S.

1985-01-01

Identifies three sources of reporting deficiency for meta-analytic results: quality (adequacy) of publicizing; quality of macrolevel reporting, and quality of microlevel reporting. Reanalysis of 25 reports from the Smith, Glass and Miller (1980) psychotherapy meta-analysis established two sources of misinformation, interrater reliabilities and…

Prevalence of attention deficit hyperactivity disorder among children and adolescents in Spain: a systematic review and meta-analysis of epidemiological studies

PubMed Central

2012-01-01

Background Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in childhood, but the frequency of the condition is not well established in many countries. The aim of the present study was to quantify the overall prevalence of ADHD among children and adolescents in Spain by means of a systematic review and meta-analysis. Methods PubMed/MEDLINE, IME, IBECS and TESEO were comprehensively searched. Original reports were selected if they provided data on prevalence estimates of ADHD among people under 18 years old in Spain and were cross-sectional, observational epidemiological studies. Information from included studies was systematically extracted and evaluated. Overall pooled-prevalence estimates of ADHD were calculated using random-effects models. Sources of heterogeneity were explored by means sub-groups analyses and univariate meta-regressions. Results Fourteen epidemiological studies (13,026 subjects) were selected. The overall pooled-prevalence of ADHD was estimated at 6.8% [95% confidence interval (CI) 4.9 – 8.8%] representing 361,580 (95% CI 260,550 – 467,927) children and adolescents in the community. There was significant heterogeneity (P < 0.001), which was incompletely explained by subgroup analyses and meta-regressions. Conclusions Our findings suggest that the prevalence of ADHD among children and adolescents in Spain is consistent with previous studies conducted in other countries and regions. This study represents a first step in estimating the national burden of ADHD that will be essential to building evidence-based programs and services. PMID:23057832

Quantitative Trait Loci for Resistance to Aspergillus Ear Rot: Analysis by Linkage Mapping, Characterization of Near-Isogenic Lines and Meta-Analysis

USDA-ARS?s Scientific Manuscript database

High levels of aflatoxin contamination of maize can be deadly for exposed human populations. Resistance to aflatoxin accumulation in maize has been reported in multiple studies and acts at multiple steps where there is fungal-plant interaction. In this study, we report the identification and mapping...

Does the use of consumer health information technology improve outcomes in the patient self-management of diabetes? A meta-analysis and narrative review of randomized controlled trials.

PubMed

Or, Calvin K L; Tao, Da

2014-05-01

To assess whether the use of consumer health information technologies (CHITs) improves outcomes in the patient self-management of diabetes. The evidence from randomized controlled trials (RCTs) on the effects of CHITs on patient outcomes was analyzed using either meta-analysis or a narrative synthesis approach. A systematic search of seven electronic databases was conducted to identify relevant reports of RCTs for the analysis. In the meta-analyses, standardized mean differences in patient outcomes were calculated and random-effects models were applied in cases where the heterogeneity of the results was moderate or high, otherwise fixed-effects models were used. Sixty-two studies, representing 67 RCTs, met the inclusion criteria. The results of the meta-analyses showed that the use of CHITs was associated with significant reductions in HbA1c, blood pressure, total cholesterol, and triglycerides levels when compared with the usual care. The findings from the narrative synthesis indicated that only a small proportion of the trials reported positive effects of CHITs on patient outcomes. The use of CHITs in supporting diabetes self-management appears to have potential benefits for patients' self-management of diabetes. However, the effectiveness of the technologies in improving patient outcomes still awaits confirmation in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Basic Lessons in ORA and AutoMap 2011

DTIC Science & Technology

2011-06-13

A small legend also appears. Below is a screen capture showing the visualization of the agent x event graph from the Stargate Summit Meta-Network...4 The visualization displays the connections between all items in the Stargate Summit Meta-Network. The red circles represent the agents, the...It takes the examples I used for the Stargate dataset. 5 lessons - 201-207 A step by step run through of creating the Meta-Network from

Predictive distributions for between-study heterogeneity and simple methods for their application in Bayesian meta-analysis

PubMed Central

Turner, Rebecca M; Jackson, Dan; Wei, Yinghui; Thompson, Simon G; Higgins, Julian P T

2015-01-01

Numerous meta-analyses in healthcare research combine results from only a small number of studies, for which the variance representing between-study heterogeneity is estimated imprecisely. A Bayesian approach to estimation allows external evidence on the expected magnitude of heterogeneity to be incorporated. The aim of this paper is to provide tools that improve the accessibility of Bayesian meta-analysis. We present two methods for implementing Bayesian meta-analysis, using numerical integration and importance sampling techniques. Based on 14 886 binary outcome meta-analyses in the Cochrane Database of Systematic Reviews, we derive a novel set of predictive distributions for the degree of heterogeneity expected in 80 settings depending on the outcomes assessed and comparisons made. These can be used as prior distributions for heterogeneity in future meta-analyses. The two methods are implemented in R, for which code is provided. Both methods produce equivalent results to standard but more complex Markov chain Monte Carlo approaches. The priors are derived as log-normal distributions for the between-study variance, applicable to meta-analyses of binary outcomes on the log odds-ratio scale. The methods are applied to two example meta-analyses, incorporating the relevant predictive distributions as prior distributions for between-study heterogeneity. We have provided resources to facilitate Bayesian meta-analysis, in a form accessible to applied researchers, which allow relevant prior information on the degree of heterogeneity to be incorporated. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:25475839

Digital Games, Design, and Learning: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Clark, Douglas B.; Tanner-Smith, Emily E.; Killingsworth, Stephen S.

2016-01-01

In this meta-analysis, we systematically reviewed research on digital games and learning for K-16 students. We synthesized comparisons of game versus nongame conditions (i.e., media comparisons) and comparisons of augmented games versus standard game designs (i.e., value-added comparisons). We used random-effects meta-regression models with robust…

Simulation-based sensitivity analysis for non-ignorably missing data.

PubMed

Yin, Peng; Shi, Jian Q

2017-01-01

Sensitivity analysis is popular in dealing with missing data problems particularly for non-ignorable missingness, where full-likelihood method cannot be adopted. It analyses how sensitively the conclusions (output) may depend on assumptions or parameters (input) about missing data, i.e. missing data mechanism. We call models with the problem of uncertainty sensitivity models. To make conventional sensitivity analysis more useful in practice we need to define some simple and interpretable statistical quantities to assess the sensitivity models and make evidence based analysis. We propose a novel approach in this paper on attempting to investigate the possibility of each missing data mechanism model assumption, by comparing the simulated datasets from various MNAR models with the observed data non-parametrically, using the K-nearest-neighbour distances. Some asymptotic theory has also been provided. A key step of this method is to plug in a plausibility evaluation system towards each sensitivity parameter, to select plausible values and reject unlikely values, instead of considering all proposed values of sensitivity parameters as in the conventional sensitivity analysis method. The method is generic and has been applied successfully to several specific models in this paper including meta-analysis model with publication bias, analysis of incomplete longitudinal data and mean estimation with non-ignorable missing data.

A meta-analysis of the relationship between rational beliefs and psychological distress.

PubMed

Oltean, Horea-Radu; David, Daniel Ovidiu

2018-06-01

 Rational emotive behavior therapy (REBT) model of psychological health assumes that rational beliefs cause functional emotions and adaptive behavior, but the presumed role of rational beliefs as protective factor against psychological distress/disorders is still in debate. An important step in validating an evidence-based therapy is to investigate the underling theoretical assumptions. Thus, the aim of the present meta-analysis is to investigate the direction and magnitude of the relationship between rational beliefs and psychological distress.  Our search identified 26 studies that met our criteria. We evaluated the effect size using the random-effects model and we tested the moderator role of several variables. The overall results revealed a medium negative association between rational beliefs and psychological distress, r = -0.31. The strongest association was found for unconditional acceptance beliefs (r = -0.41). The results add empirical evidence for the underling theory of REBT and revealed that the strength of the association between rational beliefs and distress is robust for a wide range of emotional problems. Therefore, rational beliefs could be a trans-diagnostic protective factor against distress. Moreover, results emphasized that rational beliefs type is an important factor, suggesting an increased focus in therapy on the developing of unconditional acceptance and self-acceptance beliefs. © 2017 Wiley Periodicals, Inc.

Sugar-sweetened beverage consumption, correlates and interventions among Australian Aboriginal and Torres Strait Islander communities: a scoping review protocol

PubMed Central

Avery, Jodie C; Bowden, Jacqueline A; Dono, Joanne; Gibson, Odette R; Brownbill, Aimee; Keech, Wendy; Miller, Caroline L

2017-01-01

Introduction Aboriginal and Torres Strait Islander communities of Australia experience poorer health outcomes in the areas of overweight and obesity, diabetes and cardiovascular disease. Contributing to this burden of disease in the Australian community generally and in Aboriginal and Torres Strait Islander communities, is the consumption of sugar-sweetened beverages (SSBs). We have described a protocol for a review to systematically scope articles that document use of SSBs and interventions to reduce their consumption with Aboriginal and Torres Strait Islander people. These results will inform future work that investigates interventions aimed at reducing harm associated with SSB consumption. Methods and analysis This scoping review draws on a methodology that uses a six-step approach to search databases including PubMed, SCOPUS, CINAHL, Informit (including Informit: Indigenous Peoples), Joanna Briggs Institute EBP Database and Mura, between January 1980 and February 2017. Two reviewers will be engaged to search for and screen studies independently, using formulated selection criteria, for inclusion in our review. We will include primary research studies, systematic reviews including meta-analysis or meta-synthesis, reports and unpublished grey literature. Results will be entered into a table identifying study details and characteristics, summarised using a Preferred Reporting Items for Systematic Reviews and Meta-Analysis chart and then critically analysed. Ethics and dissemination This review will not require ethics committee review. Results will be disseminated at appropriate scientific meetings, as well as through the Aboriginal and Torres Strait Islander community. PMID:28760797

Alcohol Intake and Risk of Thyroid Cancer: A Meta-Analysis of Observational Studies

PubMed Central

Hong, Seung-Hee; Myung, Seung-Kwon; Kim, Hyeon Suk

2017-01-01

Purpose The purpose of this study was to assess whether alcohol intake is associated with the risk of thyroid cancer by a meta-analysis of observational studies. Materials and Methods We searched PubMed and EMBASE in June of 2015 to locate eligible studies. We included observational studies such as cross-sectional studies, case-control studies, and cohort studies reporting odd ratios (ORs) or relative risk (RRs) with 95% confidence intervals (CIs). Results We included 33 observational studies with two cross-sectional studies, 20 case-controls studies, and 11 cohort studies, which involved a total of 7,725 thyroid cancer patients and 3,113,679 participants without thyroid cancer in the final analysis. In the fixed-effect model meta-analysis of all 33 studies, we found that alcohol intake was consistently associated with a decreased risk of thyroid cancer (OR or RR, 0.74; 95% CI, 0.67 to 0.83; I2=38.6%). In the subgroup meta-analysis by type of study, alcohol intake also decreased the risk of thyroid cancer in both case-control studies (OR, 0.77; 95% CI, 0.65 to 0.92; I2=29.5%; n=20) and cohort studies (RR, 0.70; 95% CI, 0.60 to 0.82; I2=0%; n=11). Moreover, subgroup meta-analyses by type of thyroid cancer, gender, amount of alcohol consumed, and methodological quality of study showed that alcohol intake was significantly associated with a decreased risk of thyroid cancer. Conclusion The current meta-analysis of observational studies found that, unlike most of other types of cancer, alcohol intake decreased the risk of thyroid cancer. PMID:27456949

Intermittent Cervical Traction for Treating Neck Pain: A Meta-analysis of Randomized Controlled Trials.

PubMed

Yang, Jheng-Dao; Tam, Ka-Wai; Huang, Tsai-Wei; Huang, Shih-Wei; Liou, Tsan-Hon; Chen, Hung-Chou

2017-07-01

A meta-analysis. The aim of this study was to perform a comprehensive search of current literature and conduct a meta-analysis of randomized controlled trials (RCTs) to assess the neck pain relieving effect of intermittent cervical traction (ICT). Neck pain is a common and disabling problem with a high prevalence in general population. It causes a considerable burden on the health care system with a substantial expenditure. ICT is a common component of physical therapy for neck pain in the outpatient clinic. However, the evidence regarding the effectiveness of ICT for neck pain is insufficient. Data were obtained from the PubMed, Cochrane Library, Embase, and Scopus databases from the database inception date to July 02, 2016. RCTs reporting the effects of ICT on neck pain, including those comparing the effects of ICT with those of a placebo treatment, were included. Two reviewers independently reviewed the studies, conducted a risk of bias assessment, and extracted data. The data were pooled in a meta-analysis by using a random-effects model. The meta-analysis included seven RCTs. The results indicated that patients who received ICT for neck pain had significantly lower pain scores than those receiving placebos did immediately after treatment (standardized mean difference = -0.26, 95% confidence interval = -0.46 to -0.07). The pain scores during the follow-up period and the neck disability index scores immediately after treatment and during the follow-up period did not differ significantly. ICT may have a short-term neck pain-relieving effect. Some risks of bias were noted in the included studies, reducing the evidence level of this meta-analysis. Additional high-quality RCTs are required to clarify the long-term effects of ICT on neck pain. 1.

How Efficacious is Danshen (Salvia miltiorrhiza) Dripping Pill in Treating Angina Pectoris? Evidence Assessment for Meta-Analysis of Randomized Controlled Trials.

PubMed

Jia, Yongliang; Leung, Siu-Wai

2017-09-01

More than 230 randomized controlled trials (RCTs) of danshen dripping pill (DSP) and isosorbide dinitrate (ISDN) in treating angina pectoris after the first preferred reporting items for systematic reviews and meta-analyses-compliant comprehensive meta-analysis were published in 2010. Other meta-analyses had flaws in study selection, statistical meta-analysis, and evidence assessment. This study completed the meta-analysis with an extensive assessment of the evidence. RCTs published from 1994 to 2016 on DSP and ISDN in treating angina pectoris for at least 4 weeks were included. The risk of bias (RoB) of included RCTs was assessed with the Cochrane's tool for assessing RoB. Meta-analyses based on a random-effects model were performed on two outcome measures: symptomatic (SYM) and electrocardiography (ECG) improvements. Subgroup analysis, sensitivity analysis, metaregression, and publication bias analysis were also conducted. The evidence strength was evaluated with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Among the included 109 RCTs with 11,973 participants, 49 RCTs and 5042 participants were new (after 2010). The RoB of included RCTs was high in randomization and blinding. Overall effect sizes in odds ratios for DSP over ISDN were 2.94 (95% confidence interval [CI]: 2.53-3.41) on SYM (n = 108) and 2.37 (95% CI: 2.08-2.69) by ECG (n = 81) with significant heterogeneities (I 2  = 41%, p < 0.0001 on SYM and I 2  = 44%, p < 0.0001 on ECG). Subgroup, sensitivity, and metaregression analyses showed consistent results without publication bias. However, the evidence strength was low in GRADE. The efficacy of DSP was still better than ISDN in treating angina pectoris, but the confidence decreased due to high RoB and heterogeneities.

Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies.

PubMed

Wu, Q; Liu, B; Tonmoy, S

2018-03-12

This meta-analysis pooled results from 23 qualifying individual cohort studies and found that depression was significantly associated with an increased risk of fractures and bone loss. The association between depression and risk of fracture remains controversial. We conducted a comprehensive meta-analysis to examine the effect of depression on the risk of osteoporotic fractures and bone loss. We searched databases and reviewed citations in relevant articles for eligible cohort studies. Two investigators independently conducted study selection, appraisal, and data abstraction through the use of a standardized protocol. Random effect models were used for meta-analysis. Cochrane Q and I 2 statistics were used to assess heterogeneity. Funnel plots and rank correlation tests were used to evaluate publication bias. Twenty-three studies were included for meta-analysis. In studies that reported hazard ratio (HR) as the outcome (nine studies [n = 309,862]), depression was associated with 26% increase in fracture risk (HR = 1.26, 95% CI, 1.10-1.43, p < 0.001). Studies that reported risk ratio (RR) as the outcome (seven studies [n = 64,975]) suggested that depression was associated with 39% increase in fracture risk (RR = 1.39, 95% CI, 1.19-1.62, p < 0.001). Among studies that reported hip bone mineral density (BMD) as an outcome (eight studies [n = 15,442]), depression was associated with a reduced mean annual bone loss rate of 0.35% (0.18-0.53%, p < 0.001). The increased risk of fracture and bone loss associated with depression was consistent in all meta-analysis having modified inclusion criteria and in different subgroup analyses as well. Significant heterogeneity was observed in the meta-analysis; however, no significant publication bias was detected. Depression is associated with a significant increased risk in fracture and bone loss. Effective prevention may decrease such risk.

Association between vasectomy and risk of testicular cancer: A systematic review and meta-analysis.

PubMed

Duan, Haifeng; Deng, Tuo; Chen, Yiwen; Zhao, Zhijian; Wen, Yaoan; Chen, Yeda; Li, Xiaohang; Zeng, Guohua

2018-01-01

A number of researchers have reported that vasectomy is a risk factor for testicular cancer. However, this conclusion is inconsistent with a number of other published articles. Hence, we conducted this meta-analysis to assess whether vasectomy increases the risk of testicular cancer. We identified all related studies by searching the PubMed, Embase, and Cochrane Library database from January 01, 1980 to June 01, 2017. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Summarized odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the difference in outcomes between case and control groups. Subgroup analyses were performed according to the study design and country. A total of eight studies (2176 testicular cancer patients) were included in this systematic review and meta-analysis. Six articles were case-control studies, and two were cohort studies. The pooled estimate of the OR was 1.10 (95% CI: 0.93-1.30) based on the eight studies in a fixed effects model. Two subgroup analyses were performed according to the study design and country. The results were consistent with the overall findings. Publication bias was detected by Begg's test and Egger's test and p values > 0.05, respectively. Our meta-analysis suggested that there was no association between vasectomy and the development of testicular cancer. More high-quality studies are warranted to further explore the association between vasectomy and risk of testicular cancer.

Demographic Faultlines: A Meta-Analysis of the Literature

ERIC Educational Resources Information Center

Thatcher, Sherry M. B.; Patel, Pankaj C.

2011-01-01

We propose and test a theoretical model focusing on antecedents and consequences of demographic faultlines. We also posit contingencies that affect overall team dynamics in the context of demographic faultlines, such as the study setting and performance measurement. Using meta-analysis structural equation modeling with a final data set consisting…

Meta-Analysis of Scale Reliability Using Latent Variable Modeling

ERIC Educational Resources Information Center

Raykov, Tenko; Marcoulides, George A.

2013-01-01

A latent variable modeling approach is outlined that can be used for meta-analysis of reliability coefficients of multicomponent measuring instruments. Important limitations of efforts to combine composite reliability findings across multiple studies are initially pointed out. A reliability synthesis procedure is discussed that is based on…

Eliciting mixed emotions: a meta-analysis comparing models, types, and measures.

PubMed

Berrios, Raul; Totterdell, Peter; Kellett, Stephen

2015-01-01

The idea that people can experience two oppositely valenced emotions has been controversial ever since early attempts to investigate the construct of mixed emotions. This meta-analysis examined the robustness with which mixed emotions have been elicited experimentally. A systematic literature search identified 63 experimental studies that instigated the experience of mixed emotions. Studies were distinguished according to the structure of the underlying affect model-dimensional or discrete-as well as according to the type of mixed emotions studied (e.g., happy-sad, fearful-happy, positive-negative). The meta-analysis using a random-effects model revealed a moderate to high effect size for the elicitation of mixed emotions (d IG+ = 0.77), which remained consistent regardless of the structure of the affect model, and across different types of mixed emotions. Several methodological and design moderators were tested. Studies using the minimum index (i.e., the minimum value between a pair of opposite valenced affects) resulted in smaller effect sizes, whereas subjective measures of mixed emotions increased the effect sizes. The presence of more women in the samples was also associated with larger effect sizes. The current study indicates that mixed emotions are a robust, measurable and non-artifactual experience. The results are discussed in terms of the implications for an affect system that has greater versatility and flexibility than previously thought.

Air Pollution and Quality of Sperm: A Meta-Analysis

PubMed Central

Fathi Najafi, Tahereh; Latifnejad Roudsari, Robab; Namvar, Farideh; Ghavami Ghanbarabadi, Vahid; Hadizadeh Talasaz, Zahra; Esmaeli, Mahin

2015-01-01

Context: Air pollution is common in all countries and affects reproductive functions in men and women. It particularly impacts sperm parameters in men. This meta-analysis aimed to examine the impact of air pollution on the quality of sperm. Evidence Acquisition: The scientific databases of Medline, PubMed, Scopus, Google scholar, Cochrane Library, and Elsevier were searched to identify relevant articles published between 1978 to 2013. In the first step, 76 articles were selected. These studies were ecological correlation, cohort, retrospective, cross-sectional, and case control ones that were found through electronic and hand search of references about air pollution and male infertility. The outcome measurement was the change in sperm parameters. A total of 11 articles were ultimately included in a meta-analysis to examine the impact of air pollution on sperm parameters. The authors applied meta-analysis sheets from Cochrane library, then data extraction, including mean and standard deviation of sperm parameters were calculated and finally their confidence interval (CI) were compared to CI of standard parameters. Results: The CI for pooled means were as follows: 2.68 ± 0.32 for ejaculation volume (mL), 62.1 ± 15.88 for sperm concentration (million per milliliter), 39.4 ± 5.52 for sperm motility (%), 23.91 ± 13.43 for sperm morphology (%) and 49.53 ± 11.08 for sperm count. Conclusions: The results of this meta-analysis showed that air pollution reduces sperm motility, but has no impact on the other sperm parameters of spermogram. PMID:26023349

Air pollution and quality of sperm: a meta-analysis.

PubMed

Fathi Najafi, Tahereh; Latifnejad Roudsari, Robab; Namvar, Farideh; Ghavami Ghanbarabadi, Vahid; Hadizadeh Talasaz, Zahra; Esmaeli, Mahin

2015-04-01

Air pollution is common in all countries and affects reproductive functions in men and women. It particularly impacts sperm parameters in men. This meta-analysis aimed to examine the impact of air pollution on the quality of sperm. The scientific databases of Medline, PubMed, Scopus, Google scholar, Cochrane Library, and Elsevier were searched to identify relevant articles published between 1978 to 2013. In the first step, 76 articles were selected. These studies were ecological correlation, cohort, retrospective, cross-sectional, and case control ones that were found through electronic and hand search of references about air pollution and male infertility. The outcome measurement was the change in sperm parameters. A total of 11 articles were ultimately included in a meta-analysis to examine the impact of air pollution on sperm parameters. The authors applied meta-analysis sheets from Cochrane library, then data extraction, including mean and standard deviation of sperm parameters were calculated and finally their confidence interval (CI) were compared to CI of standard parameters. The CI for pooled means were as follows: 2.68 ± 0.32 for ejaculation volume (mL), 62.1 ± 15.88 for sperm concentration (million per milliliter), 39.4 ± 5.52 for sperm motility (%), 23.91 ± 13.43 for sperm morphology (%) and 49.53 ± 11.08 for sperm count. The results of this meta-analysis showed that air pollution reduces sperm motility, but has no impact on the other sperm parameters of spermogram.

Do community specialist palliative care services that provide home nursing increase rates of home death for people with life-limiting illnesses? A systematic review and meta-analysis of comparative studies.

PubMed

Luckett, Tim; Davidson, Patricia M; Lam, Lawrence; Phillips, Jane; Currow, David C; Agar, Meera

2013-02-01

Systematic reviews and meta-analyses suggest that community specialist palliative care services (SPCSs) can avoid hospitalizations and enable home deaths. But more information is needed regarding the relative efficacies of different models. Family caregivers highlight home nursing as the most important service, but it is also likely the most costly. To establish whether community SPCSs offering home nursing increase rates of home death compared with other models. We searched MEDLINE, AMED, Embase, CINAHL, the Cochrane Database of Systematic Reviews, and CENTRAL on March 2 and 3, 2011. To be eligible, articles had to be published in English-language peer-reviewed journals and report original research comparing the effect on home deaths of SPCSs providing home nursing vs. any alternative. Study quality was independently rated using Cochrane grades. Maximum likelihood estimation of heterogeneity was used to establish the method for meta-analysis (fixed or random effects). Potential biases were assessed. Of 1492 articles screened, 10 articles were found eligible, reporting nine studies that yielded data for 10 comparisons. Study quality was high in two cases, moderate in three and low in four. Meta-analysis indicated a significant effect for SPCSs with home nursing (odds ratio 4.45, 95% CI 3.24-6.11; P<0.001). However, the high-quality studies found no effect (odds ratio 1.40, 95% CI 0.97-2.02; P=0.071). Bias was minimal. A meta-analysis found evidence to be inconclusive that community SPCSs that offer home nursing increase home deaths without compromising symptoms or increasing costs. But a compelling trend warrants further confirmatory studies. Future trials should compare the relative efficacy of different models and intensities of SPCSs. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review.

PubMed

Weir, Christopher J; Butcher, Isabella; Assi, Valentina; Lewis, Stephanie C; Murray, Gordon D; Langhorne, Peter; Brady, Marian C

2018-03-07

Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses.

Global sensitivity analysis of a local water balance model predicting evaporation, water yield and drought

NASA Astrophysics Data System (ADS)

Speich, Matthias; Zappa, Massimiliano; Lischke, Heike

2017-04-01

Evaporation and transpiration affect both catchment water yield and the growing conditions for vegetation. They are driven by climate, but also depend on vegetation, soil and land surface properties. In hydrological and land surface models, these properties may be included as constant parameters, or as state variables. Often, little is known about the effect of these variables on model outputs. In the present study, the effect of surface properties on evaporation was assessed in a global sensitivity analysis. To this effect, we developed a simple local water balance model combining state-of-the-art process formulations for evaporation, transpiration and soil water balance. The model is vertically one-dimensional, and the relative simplicity of its process formulations makes it suitable for integration in a spatially distributed model at regional scale. The main model outputs are annual total evaporation (TE, i.e. the sum of transpiration, soil evaporation and interception), and a drought index (DI), which is based on the ratio of actual and potential transpiration. This index represents the growing conditions for forest trees. The sensitivity analysis was conducted in two steps. First, a screening analysis was applied to identify unimportant parameters out of an initial set of 19 parameters. In a second step, a statistical meta-model was applied to a sample of 800 model runs, in which the values of the important parameters were varied. Parameter effect and interactions were analyzed with effects plots. The model was driven with forcing data from ten meteorological stations in Switzerland, representing a wide range of precipitation regimes across a strong temperature gradient. Of the 19 original parameters, eight were identified as important in the screening analysis. Both steps highlighted the importance of Plant Available Water Capacity (AWC) and Leaf Area Index (LAI). However, their effect varies greatly across stations. For example, while a transition from a sparse to a closed forest canopy has almost no effect on annual TE at warm and dry sites, it increases TE by up to 100 mm/year at cold-humid and warm-humid sites. Further parameters of importance describe infiltration, as well as canopy resistance and its response to environmental variables. This study offers insights for future development of hydrological and ecohydrological models. First, it shows that although local water balance is primarily controlled by climate, the vegetation and soil parameters may have a large impact on the outputs. Second, it indicates that modeling studies should prioritize a realistic parameterization of LAI and AWC, while other parameters may be set to fixed values. Third, it illustrates to which extent parameter effect and interactions depend on local climate.

Two-stage open reduction and internal fixation versus limited internal fixation combined with external fixation: a meta-analysis of postoperative complications in patients with severe Pilon fractures.

PubMed

Cui, Xueliang; Chen, Hui; Rui, Yunfeng; Niu, Yang; Li, He

2018-01-01

Objectives Two-stage open reduction and internal fixation (ORIF) and limited internal fixation combined with external fixation (LIFEF) are two widely used methods to treat Pilon injury. However, which method is superior to the other remains controversial. This meta-analysis was performed to quantitatively compare two-stage ORIF and LIFEF and clarify which method is better with respect to postoperative complications in the treatment of tibial Pilon fractures. Methods We conducted a meta-analysis to quantitatively compare the postoperative complications between two-stage ORIF and LIFEF. Eight studies involving 360 fractures in 359 patients were included in the meta-analysis. Results The two-stage ORIF group had a significantly lower risk of superficial infection, nonunion, and bone healing problems than the LIFEF group. However, no significant differences in deep infection, delayed union, malunion, arthritis symptoms, or chronic osteomyelitis were found between the two groups. Conclusion Two-stage ORIF was associated with a lower risk of postoperative complications with respect to superficial infection, nonunion, and bone healing problems than LIFEF for tibial Pilon fractures. Level of evidence 2.

Modern meta-heuristics based on nonlinear physics processes: A review of models and design procedures

NASA Astrophysics Data System (ADS)

Salcedo-Sanz, S.

2016-10-01

Meta-heuristic algorithms are problem-solving methods which try to find good-enough solutions to very hard optimization problems, at a reasonable computation time, where classical approaches fail, or cannot even been applied. Many existing meta-heuristics approaches are nature-inspired techniques, which work by simulating or modeling different natural processes in a computer. Historically, many of the most successful meta-heuristic approaches have had a biological inspiration, such as evolutionary computation or swarm intelligence paradigms, but in the last few years new approaches based on nonlinear physics processes modeling have been proposed and applied with success. Non-linear physics processes, modeled as optimization algorithms, are able to produce completely new search procedures, with extremely effective exploration capabilities in many cases, which are able to outperform existing optimization approaches. In this paper we review the most important optimization algorithms based on nonlinear physics, how they have been constructed from specific modeling of a real phenomena, and also their novelty in terms of comparison with alternative existing algorithms for optimization. We first review important concepts on optimization problems, search spaces and problems' difficulty. Then, the usefulness of heuristics and meta-heuristics approaches to face hard optimization problems is introduced, and some of the main existing classical versions of these algorithms are reviewed. The mathematical framework of different nonlinear physics processes is then introduced as a preparatory step to review in detail the most important meta-heuristics based on them. A discussion on the novelty of these approaches, their main computational implementation and design issues, and the evaluation of a novel meta-heuristic based on Strange Attractors mutation will be carried out to complete the review of these techniques. We also describe some of the most important application areas, in broad sense, of meta-heuristics, and describe free-accessible software frameworks which can be used to make easier the implementation of these algorithms.

Association between type 1 diabetes mellitus and risk of epilepsy: A meta-analysis of observational studies.

PubMed

Yan, Dandan; Zhao, Enfa; Zhang, Hong; Luo, Xiaohui; Du, Yajuan

2017-01-01

A potential association between type 1 diabetes mellitus and subsequent epilepsy emerged in recent studies. This study aimed to evaluate the possible relationship between type 1 diabetes mellitus and epilepsy using meta-analysis. Pubmed, ISI Web of Knowledge, Embase and Cochrane Library were searched for potential studies of the association between type 1 diabetes mellitus and epilepsy from inception to February 1, 2017. Two investigators independently screened studies for inclusion and extracted related data; discrepancies were solved by consensus. Random effects model of Hazard Ratio (HR) was used to estimate the strength of association. We identified 13 papers from potentially relevant articles of which 3 cohort studies met the inclusion criteria. Random effects meta-analysis showed that type 1 diabetes mellitus was associated with an increased risk of epilepsy with HR = 3.29 (95% CI: 2.61-4.14; I 2 = 0, p = 0.689). Similar results were observed in type 1 diabetes mellitus patents younger than 18-years-old with HR = 2.96 (95% CI: 2.28-3.84; I 2 = 0, p = 0.571). Meta-analysis of 2 studies that adjusted for potential confounders yielded an increased risk of epilepsy with HR = 2.89 (95% CI: 2.26-3.70; I 2 = 0, p = 0.831). The meta-analysis indicates that type 1 diabetes mellitus is associated with a statistically significant increased risk for epilepsy compared to those without type 1 diabetes mellitus.

Identification of Cost Indicators with Significant Economic Impact on the Total Treatment Costs of Chronic Heart Failure Patients - A Meta-Analysis.

PubMed

Hameed, Ahmed S; Modre-Osprian, Robert; Schreier, Günter

2017-01-01

Increasing treatment costs of HF patients affect the initiation of appropriate treatment method. Divergent approaches to measure the costs of treatment and the lack of common cost indicators impede the comparison of therapy settings. In the context of the present meta-analysis, key cost indicators from the perspective of healthcare providers are to be identified, described, analyzed and quantified. This review helps narrowing down the cost indicators, which have the most significant economic impact on the total treatment costs of HF patients. Telemedical services are to be compared to standard therapy methods. The identification process was based on several steps. For the quantitative synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An additional set of criteria was defined for the following qualitative analysis. 5 key cost indicators were identified with significant economic impact on the treatment costs of HF patients. 95% of the reported treatment costs could be captured based on the identified cost indicators.

A simulations approach for meta-analysis of genetic association studies based on additive genetic model.

PubMed

John, Majnu; Lencz, Todd; Malhotra, Anil K; Correll, Christoph U; Zhang, Jian-Ping

2018-06-01

Meta-analysis of genetic association studies is being increasingly used to assess phenotypic differences between genotype groups. When the underlying genetic model is assumed to be dominant or recessive, assessing the phenotype differences based on summary statistics, reported for individual studies in a meta-analysis, is a valid strategy. However, when the genetic model is additive, a similar strategy based on summary statistics will lead to biased results. This fact about the additive model is one of the things that we establish in this paper, using simulations. The main goal of this paper is to present an alternate strategy for the additive model based on simulating data for the individual studies. We show that the alternate strategy is far superior to the strategy based on summary statistics.

Design and Analysis of an X-Ray Mirror Assembly Using the Meta-Shell Approach

NASA Technical Reports Server (NTRS)

McClelland, Ryan S.; Bonafede, Joseph; Saha, Timo T.; Solly, Peter M.; Zhang, William W.

2016-01-01

Lightweight and high resolution optics are needed for future space-based x-ray telescopes to achieve advances in high-energy astrophysics. Past missions such as Chandra and XMM-Newton have achieved excellent angular resolution using a full shell mirror approach. Other missions such as Suzaku and NuSTAR have achieved lightweight mirrors using a segmented approach. This paper describes a new approach, called meta-shells, which combines the fabrication advantages of segmented optics with the alignment advantages of full shell optics. Meta-shells are built by layering overlapping mirror segments onto a central structural shell. The resulting optic has the stiffness and rotational symmetry of a full shell, but with an order of magnitude greater collecting area. Several meta-shells so constructed can be integrated into a large x-ray mirror assembly by proven methods used for Chandra and XMM-Newton. The mirror segments are mounted to the meta-shell using a novel four point semi-kinematic mount. The four point mount deterministically locates the segment in its most performance sensitive degrees of freedom. Extensive analysis has been performed to demonstrate the feasibility of the four point mount and meta-shell approach. A mathematical model of a meta-shell constructed with mirror segments bonded at four points and subject to launch loads has been developed to determine the optimal design parameters, namely bond size, mirror segment span, and number of layers per meta-shell. The parameters of an example 1.3 m diameter mirror assembly are given including the predicted effective area. To verify the mathematical model and support opto-mechanical analysis, a detailed finite element model of a meta-shell was created. Finite element analysis predicts low gravity distortion and low sensitivity to thermal gradients.

Living systematic reviews: 3. Statistical methods for updating meta-analyses.

PubMed

Simmonds, Mark; Salanti, Georgia; McKenzie, Joanne; Elliott, Julian

2017-11-01

A living systematic review (LSR) should keep the review current as new research evidence emerges. Any meta-analyses included in the review will also need updating as new material is identified. If the aim of the review is solely to present the best current evidence standard meta-analysis may be sufficient, provided reviewers are aware that results may change at later updates. If the review is used in a decision-making context, more caution may be needed. When using standard meta-analysis methods, the chance of incorrectly concluding that any updated meta-analysis is statistically significant when there is no effect (the type I error) increases rapidly as more updates are performed. Inaccurate estimation of any heterogeneity across studies may also lead to inappropriate conclusions. This paper considers four methods to avoid some of these statistical problems when updating meta-analyses: two methods, that is, law of the iterated logarithm and the Shuster method control primarily for inflation of type I error and two other methods, that is, trial sequential analysis and sequential meta-analysis control for type I and II errors (failing to detect a genuine effect) and take account of heterogeneity. This paper compares the methods and considers how they could be applied to LSRs. Copyright © 2017 Elsevier Inc. All rights reserved.

The Hard but Necessary Task of Gathering Order-One Effect Size Indices in Meta-Analysis

ERIC Educational Resources Information Center

Ortego, Carmen; Botella, Juan

2010-01-01

Meta-analysis of studies with two groups and two measurement occasions must employ order-one effect size indices to represent study outcomes. Especially with non-random assignment, non-equivalent control group designs, a statistical analysis restricted to post-treatment scores can lead to severely biased conclusions. The 109 primary studies…

Multilevel mixed effects parametric survival models using adaptive Gauss-Hermite quadrature with application to recurrent events and individual participant data meta-analysis.

PubMed

Crowther, Michael J; Look, Maxime P; Riley, Richard D

2014-09-28

Multilevel mixed effects survival models are used in the analysis of clustered survival data, such as repeated events, multicenter clinical trials, and individual participant data (IPD) meta-analyses, to investigate heterogeneity in baseline risk and covariate effects. In this paper, we extend parametric frailty models including the exponential, Weibull and Gompertz proportional hazards (PH) models and the log logistic, log normal, and generalized gamma accelerated failure time models to allow any number of normally distributed random effects. Furthermore, we extend the flexible parametric survival model of Royston and Parmar, modeled on the log-cumulative hazard scale using restricted cubic splines, to include random effects while also allowing for non-PH (time-dependent effects). Maximum likelihood is used to estimate the models utilizing adaptive or nonadaptive Gauss-Hermite quadrature. The methods are evaluated through simulation studies representing clinically plausible scenarios of a multicenter trial and IPD meta-analysis, showing good performance of the estimation method. The flexible parametric mixed effects model is illustrated using a dataset of patients with kidney disease and repeated times to infection and an IPD meta-analysis of prognostic factor studies in patients with breast cancer. User-friendly Stata software is provided to implement the methods. Copyright © 2014 John Wiley & Sons, Ltd.

Body typing of children and adolescents using 3D-body scanning

PubMed Central

Vogel, Mandy; Kirsten, Toralf; Glock, Fabian; Poulain, Tanja; Körner, Antje; Loeffler, Markus; Kiess, Wieland; Binder, Hans

2017-01-01

Three-dimensional (3D-) body scanning of children and adolescents allows the detailed study of physiological development in terms of anthropometrical alterations which potentially provide early onset markers for obesity. Here, we present a systematic analysis of body scanning data of 2,700 urban children and adolescents in the age range between 5 and 18 years with the special aim to stratify the participants into distinct body shape types and to describe their change upon development. In a first step, we extracted a set of eight representative meta-measures from the data. Each of them collects a related group of anthropometrical features and changes specifically upon aging. In a second step we defined seven body types by clustering the meta-measures of all participants. These body types describe the body shapes in terms of three weight (lower, normal and overweight) and three age (young, medium and older) categories. For younger children (age of 5–10 years) we found a common ‘early childhood body shape’ which splits into three weight-dependent types for older children, with one or two years delay for boys. Our study shows that the concept of body types provides a reliable option for the anthropometric characterization of developing and aging populations. PMID:29053732

Machine Learning Meta-analysis of Large Metagenomic Datasets: Tools and Biological Insights.

PubMed

Pasolli, Edoardo; Truong, Duy Tin; Malik, Faizan; Waldron, Levi; Segata, Nicola

2016-07-01

Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction tasks using quantitative microbiome profiles, including species-level relative abundances and presence of strain-specific markers. A comprehensive meta-analysis, with particular emphasis on generalization across cohorts, was performed in a collection of 2424 publicly available metagenomic samples from eight large-scale studies. Cross-validation revealed good disease-prediction capabilities, which were in general improved by feature selection and use of strain-specific markers instead of species-level taxonomic abundance. In cross-study analysis, models transferred between studies were in some cases less accurate than models tested by within-study cross-validation. Interestingly, the addition of healthy (control) samples from other studies to training sets improved disease prediction capabilities. Some microbial species (most notably Streptococcus anginosus) seem to characterize general dysbiotic states of the microbiome rather than connections with a specific disease. Our results in modelling features of the "healthy" microbiome can be considered a first step toward defining general microbial dysbiosis. The software framework, microbiome profiles, and metadata for thousands of samples are publicly available at http://segatalab.cibio.unitn.it/tools/metaml.

Developing and validating risk prediction models in an individual participant data meta-analysis

PubMed Central

2014-01-01

Background Risk prediction models estimate the risk of developing future outcomes for individuals based on one or more underlying characteristics (predictors). We review how researchers develop and validate risk prediction models within an individual participant data (IPD) meta-analysis, in order to assess the feasibility and conduct of the approach. Methods A qualitative review of the aims, methodology, and reporting in 15 articles that developed a risk prediction model using IPD from multiple studies. Results The IPD approach offers many opportunities but methodological challenges exist, including: unavailability of requested IPD, missing patient data and predictors, and between-study heterogeneity in methods of measurement, outcome definitions and predictor effects. Most articles develop their model using IPD from all available studies and perform only an internal validation (on the same set of data). Ten of the 15 articles did not allow for any study differences in baseline risk (intercepts), potentially limiting their model’s applicability and performance in some populations. Only two articles used external validation (on different data), including a novel method which develops the model on all but one of the IPD studies, tests performance in the excluded study, and repeats by rotating the omitted study. Conclusions An IPD meta-analysis offers unique opportunities for risk prediction research. Researchers can make more of this by allowing separate model intercept terms for each study (population) to improve generalisability, and by using ‘internal-external cross-validation’ to simultaneously develop and validate their model. Methodological challenges can be reduced by prospectively planned collaborations that share IPD for risk prediction. PMID:24397587

Effect size calculation in meta-analyses of psychotherapy outcome research.

PubMed

Hoyt, William T; Del Re, A C

2018-05-01

Meta-analysis of psychotherapy intervention research normally examines differences between treatment groups and some form of comparison group (e.g., wait list control; alternative treatment group). The effect of treatment is normally quantified as a standardized mean difference (SMD). We describe procedures for computing unbiased estimates of the population SMD from sample data (e.g., group Ms and SDs), and provide guidance about a number of complications that may arise related to effect size computation. These complications include (a) incomplete data in research reports; (b) use of baseline data in computing SMDs and estimating the population standard deviation (σ); (c) combining effect size data from studies using different research designs; and (d) appropriate techniques for analysis of data from studies providing multiple estimates of the effect of interest (i.e., dependent effect sizes). Clinical or Methodological Significance of this article: Meta-analysis is a set of techniques for producing valid summaries of existing research. The initial computational step for meta-analyses of research on intervention outcomes involves computing an effect size quantifying the change attributable to the intervention. We discuss common issues in the computation of effect sizes and provide recommended procedures to address them.

The evaluation of meta-analysis techniques for quantifying prescribed fire effects on fuel loadings.

Treesearch

Karen E. Kopper; Donald McKenzie; David L. Peterson

2009-01-01

Models and effect-size metrics for meta-analysis were compared in four separate meta-analyses quantifying surface fuels after prescribed fires in ponderosa pine (Pinus ponderosa Dougl. ex Laws.) forests of the Western United States. An aggregated data set was compiled from eight published reports that contained data from 65 fire treatment units....

Improving Treatment Plan Implementation in Schools: A Meta-Analysis of Single Subject Design Studies

ERIC Educational Resources Information Center

Noell, George H.; Gansle, Kristin A.; Mevers, Joanna Lomas; Knox, R. Maria; Mintz, Joslyn Cynkus; Dahir, Amanda

2014-01-01

Twenty-nine peer-reviewed journal articles that analyzed intervention implementation in schools using single-case experimental designs were meta-analyzed. These studies reported 171 separate data paths and provided 3,991 data points. The meta-analysis was accomplished by fitting data extracted from graphs in mixed linear growth models. This…

Meta-analysis of diagnostic test data: a bivariate Bayesian modeling approach.

PubMed

Verde, Pablo E

2010-12-30

In the last decades, the amount of published results on clinical diagnostic tests has expanded very rapidly. The counterpart to this development has been the formal evaluation and synthesis of diagnostic results. However, published results present substantial heterogeneity and they can be regarded as so far removed from the classical domain of meta-analysis, that they can provide a rather severe test of classical statistical methods. Recently, bivariate random effects meta-analytic methods, which model the pairs of sensitivities and specificities, have been presented from the classical point of view. In this work a bivariate Bayesian modeling approach is presented. This approach substantially extends the scope of classical bivariate methods by allowing the structural distribution of the random effects to depend on multiple sources of variability. Meta-analysis is summarized by the predictive posterior distributions for sensitivity and specificity. This new approach allows, also, to perform substantial model checking, model diagnostic and model selection. Statistical computations are implemented in the public domain statistical software (WinBUGS and R) and illustrated with real data examples. Copyright © 2010 John Wiley & Sons, Ltd.

Effects of Teacher Professional Development on Gains in Student Achievement: How Meta Analysis Provides Scientific Evidence Useful to Education Leaders

ERIC Educational Resources Information Center

Blank, Rolf K.; de las Alas, Nina

2010-01-01

This meta analysis study focused on identifying and analyzing research studies that measured effects of teacher professional development with a content focus on math or science. This meta analysis was carried out to address two primary questions: (1) What are the effects of content-focused professional development for math and science teachers on…

Relations between CBM (Oral Reading and Maze) and Reading Comprehension on State Achievement Tests: A Meta-Analysis

ERIC Educational Resources Information Center

Shin, Jaehyun

2017-01-01

The purpose of this study was to examine the validity of two widely used Curriculum-Based Measurement (CBM) in reading--oral reading and maze task--in relation to reading comprehension on state tests using a meta-analysis. A total of 61 studies (132 correlations) were identified across Grades 1 to 10. A random-effects meta-analysis was conducted…

Teaching tools in Evidence Based Practice: evaluation of reusable learning objects (RLOs) for learning about Meta-analysis

PubMed Central

2011-01-01

Background All healthcare students are taught the principles of evidence based practice on their courses. The ability to understand the procedures used in systematically reviewing evidence reported in studies, such as meta-analysis, are an important element of evidence based practice. Meta-analysis is a difficult statistical concept for healthcare students to understand yet it is an important technique used in systematic reviews to pool data from studies to look at combined effectiveness of treatments. In other areas of the healthcare curricula, by supplementing lectures, workbooks and workshops with pedagogically designed, multimedia learning objects (known as reusable learning objects or RLOs) we have shown an improvement in students' perceived understanding in subjects they found difficult. In this study we describe the development and evaluation of two RLOs on meta-analysis. The RLOs supplement associated lectures and aim to improve students' understanding of meta-analysis in healthcare students. Methods Following a quality controlled design process two RLOs were developed and delivered to two cohorts of students, a Master in Public Health course and Postgraduate diploma in nursing course. Students' understanding of five key concepts of Meta-analysis were measured before and after a lecture and again after RLO use. RLOs were also evaluated for their educational value, learning support, media attributes and usability using closed and open questions. Results Students rated their understanding of meta-analysis as improved after a lecture and further improved after completing the RLOs (Wilcoxon paired test, p < 0.01 in all cases) Whilst the media components of the RLOs such as animations helped most students (86%) understand concepts including for example Forest plots, 93% of students rated usability and control as important to their learning. A small number of students stated they needed the support of a lecturer alongside the RLOs (7% 'Agreed' and 21% 'Neutral'). Conclusions Meta-analysis RLOs that are openly accessible and unrestricted by usernames and passwords provide flexible support for students who find the process of meta-analysis difficult. PMID:21542905

Do antipsychotics lead to cognitive impairment in dementia? A meta-analysis of randomised placebo-controlled trials.

PubMed

Wolf, Alexander; Leucht, Stefan; Pajonk, Frank-Gerald

2017-04-01

Behavioural and psychological symptoms in dementia (BPSD) are common and often treated with antipsychotics, which are known to have small efficacy and to cause many side effects. One potential side effect might be cognitive decline. We searched MEDLINE, Scopus, CENTRAL and www.ClincalStudyResult.org for randomized, double-blind, placebo-controlled trials using antipsychotics for treating BPSD and evaluated cognitive functioning. The studies identified were summarized in a meta-analysis with the standardized mean difference (SMD, Hedges's g) as the effect size. Meta-regression was additionally performed to identify associated factors. Ten studies provided data on the course of cognitive functioning. The random effects model of the pooled analysis showed a not significant effect (SMD = -0.065, 95 % CI -0.186 to 0.057, I 2  = 41 %). Meta-regression revealed a significant correlation between cognitive impairment and treatment duration (R 2  = 0.78, p < 0.02) as well as baseline MMSE (R 2  = 0.92, p < 0.005). These correlations depend on only two out of ten studies and should interpret cautiously.

A Two-Step Approach to Analyze Satisfaction Data

ERIC Educational Resources Information Center

Ferrari, Pier Alda; Pagani, Laura; Fiorio, Carlo V.

2011-01-01

In this paper a two-step procedure based on Nonlinear Principal Component Analysis (NLPCA) and Multilevel models (MLM) for the analysis of satisfaction data is proposed. The basic hypothesis is that observed ordinal variables describe different aspects of a latent continuous variable, which depends on covariates connected with individual and…

Plasma ET-1 Concentrations are Elevated in Patients with Hypertension - Meta-Analysis of Clinical Studies.

PubMed

Xu, Mei; Lu, Yong-Ping; Hasan, Ahmed Abdallah; Hocher, Berthold

2017-01-01

A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. Eleven studies fulfilling our in- and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95%CI [0.47∼2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage. © 2017 The Author(s). Published by S. Karger AG, Basel.

Complement factor H Y402H variant and risk of age-related macular degeneration in Asians: a systematic review and meta-analysis.

PubMed

Kondo, Naoshi; Bessho, Hiroaki; Honda, Shigeru; Negi, Akira

2011-02-01

To investigate whether the Y402H variant in the complement factor H gene is associated with age-related macular degeneration (AMD) in Asian populations. Meta-analysis of previous publications. Case-control groups of subjects with AMD and controls from 13 association studies. We performed a meta-analysis of the association between Y402H and AMD in Asian populations using data available from 13 case-control studies involving 3973 subjects. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed- and random-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis, cumulative meta-analysis, and meta-regression analysis were also performed. Allele and genotype frequencies of the Y402H variant. The Y402H variant showed a significant summary OR of 1.97 (95% CI, 1.54-2.52; P<0.001; allelic contrast model) per allele. Possession of at least 1 copy of the C allele increased the disease risk by 1.97-fold (95% CI, 1.63-2.39; P<0.001; dominant model) and accounted for 8.8% of the attributable risk of AMD in Asian populations. Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Meta-regression analysis indicated no significant effect of baseline study characteristics on the summary effect size. Cumulative meta-analysis revealed that the summary ORs were stable and the 95% CIs narrowed with the accumulation of data over time. Our analysis provides substantial evidence that the Y402H variant is significantly associated with AMD in Asian populations. Our results expand the number of confirmed AMD susceptibility loci for Asians populations, which provide a better understanding of the genetic architecture underlying disease susceptibility and may advance the potential for preclinical prediction in future genetic tests by a combined evaluation of inherited susceptibility with previously established loci. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Network meta-analysis of multiple outcome measures accounting for borrowing of information across outcomes.

PubMed

Achana, Felix A; Cooper, Nicola J; Bujkiewicz, Sylwia; Hubbard, Stephanie J; Kendrick, Denise; Jones, David R; Sutton, Alex J

2014-07-21

Network meta-analysis (NMA) enables simultaneous comparison of multiple treatments while preserving randomisation. When summarising evidence to inform an economic evaluation, it is important that the analysis accurately reflects the dependency structure within the data, as correlations between outcomes may have implication for estimating the net benefit associated with treatment. A multivariate NMA offers a framework for evaluating multiple treatments across multiple outcome measures while accounting for the correlation structure between outcomes. The standard NMA model is extended to multiple outcome settings in two stages. In the first stage, information is borrowed across outcomes as well across studies through modelling the within-study and between-study correlation structure. In the second stage, we make use of the additional assumption that intervention effects are exchangeable between outcomes to predict effect estimates for all outcomes, including effect estimates on outcomes where evidence is either sparse or the treatment had not been considered by any one of the studies included in the analysis. We apply the methods to binary outcome data from a systematic review evaluating the effectiveness of nine home safety interventions on uptake of three poisoning prevention practices (safe storage of medicines, safe storage of other household products, and possession of poison centre control telephone number) in households with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo (MCMC) simulations. Univariate and the first stage multivariate models produced broadly similar point estimates of intervention effects but the uncertainty around the multivariate estimates varied depending on the prior distribution specified for the between-study covariance structure. The second stage multivariate analyses produced more precise effect estimates while enabling intervention effects to be predicted for all outcomes, including intervention effects on outcomes not directly considered by the studies included in the analysis. Accounting for the dependency between outcomes in a multivariate meta-analysis may or may not improve the precision of effect estimates from a network meta-analysis compared to analysing each outcome separately.

Cohort profile: the chronic kidney disease prognosis consortium.

PubMed

Matsushita, Kunihiro; Ballew, Shoshana H; Astor, Brad C; Jong, Paul E de; Gansevoort, Ron T; Hemmelgarn, Brenda R; Levey, Andrew S; Levin, Adeera; Wen, Chi-Pang; Woodward, Mark; Coresh, Josef

2013-12-01

The Chronic Kidney Disease Prognosis Consortium (CKD-PC) was established in 2009 to provide comprehensive evidence about the prognostic impact of two key kidney measures that are used to define and stage CKD, estimated glomerular filtration rate (eGFR) and albuminuria, on mortality and kidney outcomes. CKD-PC currently consists of 46 cohorts with data on these kidney measures and outcomes from >2 million participants spanning across 40 countries/regions all over the world. CKD-PC published four meta-analysis articles in 2010-11, providing key evidence for an international consensus on the definition and staging of CKD and an update for CKD clinical practice guidelines. The consortium continues to work on more detailed analysis (subgroups, different eGFR equations, other exposures and outcomes, and risk prediction). CKD-PC preferably collects individual participant data but also applies a novel distributed analysis model, in which each cohort runs statistical analysis locally and shares only analysed outputs for meta-analyses. This distributed model allows inclusion of cohorts which cannot share individual participant level data. According to agreement with cohorts, CKD-PC will not share data with third parties, but is open to including further eligible cohorts. Each cohort can opt in/out for each topic. CKD-PC has established a productive and effective collaboration, allowing flexible participation and complex meta-analyses for studying CKD.

Meta-Analysis of a Continuous Outcome Combining Individual Patient Data and Aggregate Data: A Method Based on Simulated Individual Patient Data

ERIC Educational Resources Information Center

Yamaguchi, Yusuke; Sakamoto, Wataru; Goto, Masashi; Staessen, Jan A.; Wang, Jiguang; Gueyffier, Francois; Riley, Richard D.

2014-01-01

When some trials provide individual patient data (IPD) and the others provide only aggregate data (AD), meta-analysis methods for combining IPD and AD are required. We propose a method that reconstructs the missing IPD for AD trials by a Bayesian sampling procedure and then applies an IPD meta-analysis model to the mixture of simulated IPD and…

The meta-analytic big bang.

PubMed

Shadish, William R; Lecy, Jesse D

2015-09-01

This article looks at the impact of meta-analysis and then explores why meta-analysis was developed at the time and by the scholars it did in the social sciences in the 1970s. For the first problem, impact, it examines the impact of meta-analysis using citation network analysis. The impact is seen in the sciences, arts and humanities, and on such contemporaneous developments as multilevel modeling, medical statistics, qualitative methods, program evaluation, and single-case design. Using a constrained snowball sample of citations, we highlight key articles that are either most highly cited or most central to the systematic review network. Then, the article examines why meta-analysis came to be in the 1970s in the social sciences through the work of Gene Glass, Robert Rosenthal, and Frank Schmidt, each of whom developed similar theories of meta-analysis at about the same time. The article ends by explaining how Simonton's chance configuration theory and Campbell's evolutionary epistemology can illuminate why meta-analysis occurred with these scholars when it did and not in medical sciences. Copyright © 2015 John Wiley & Sons, Ltd.

A Systematic Review and Meta-analysis of the Association Between Giardia lamblia and Endemic Pediatric Diarrhea in Developing Countries

PubMed Central

Muhsen, Khitam; Levine, Myron M.

2012-01-01

We performed a systematic literature review and meta-analysis examining the association between diarrhea in young children in nonindustrialized settings and Giardia lamblia infection. Eligible were case/control and longitudinal studies that defined the outcome as acute or persistent (>14 days) diarrhea, adjusted for confounders and lasting for at least 1 year. Data on G. lamblia detection (mainly in stools) from diarrhea patients and controls without diarrhea were abstracted. Random effects model meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Twelve nonindustrialized-setting acute pediatric diarrhea studies met the meta-analysis inclusion criteria. Random-effects model meta-analysis of combined results (9774 acute diarrhea cases and 8766 controls) yielded a pooled OR of 0.60 (95% CI, .38–.94; P = .03), indicating that G. lamblia was not associated with acute diarrhea. However, limited data suggest that initial Giardia infections in early infancy may be positively associated with diarrhea. Meta-analysis of 5 persistent diarrhea studies showed a pooled OR of 3.18 (95% CI, 1.50–6.76; P < .001), positively linking Giardia with that syndrome. The well-powered Global Enteric Multicenter Study (GEMS) is prospectively addressing the association between G. lamblia infection and diarrhea in children in developing countries. PMID:23169940

The Trans-Contextual Model of Autonomous Motivation in Education: Conceptual and Empirical Issues and Meta-Analysis.

PubMed

Hagger, Martin S; Chatzisarantis, Nikos L D

2016-06-01

The trans-contextual model outlines the processes by which autonomous motivation toward activities in a physical education context predicts autonomous motivation toward physical activity outside of school, and beliefs about, intentions toward, and actual engagement in, out-of-school physical activity. In the present article, we clarify the fundamental propositions of the model and resolve some outstanding conceptual issues, including its generalizability across multiple educational domains, criteria for its rejection or failed replication, the role of belief-based antecedents of intentions, and the causal ordering of its constructs. We also evaluate the consistency of model relationships in previous tests of the model using path-analytic meta-analysis. The analysis supported model hypotheses but identified substantial heterogeneity in the hypothesized relationships across studies unattributed to sampling and measurement error. Based on our meta-analysis, future research needs to provide further replications of the model in diverse educational settings beyond physical education and test model hypotheses using experimental methods.

Alternative Measures of Between-Study Heterogeneity in Meta-Analysis: Reducing the Impact of Outlying Studies

PubMed Central

Lin, Lifeng; Chu, Haitao; Hodges, James S.

2016-01-01

Summary Meta-analysis has become a widely used tool to combine results from independent studies. The collected studies are homogeneous if they share a common underlying true effect size; otherwise, they are heterogeneous. A fixed-effect model is customarily used when the studies are deemed homogeneous, while a random-effects model is used for heterogeneous studies. Assessing heterogeneity in meta-analysis is critical for model selection and decision making. Ideally, if heterogeneity is present, it should permeate the entire collection of studies, instead of being limited to a small number of outlying studies. Outliers can have great impact on conventional measures of heterogeneity and the conclusions of a meta-analysis. However, no widely accepted guidelines exist for handling outliers. This article proposes several new heterogeneity measures. In the presence of outliers, the proposed measures are less affected than the conventional ones. The performance of the proposed and conventional heterogeneity measures are compared theoretically, by studying their asymptotic properties, and empirically, using simulations and case studies. PMID:27167143

Multivariate meta-analysis using individual participant data

PubMed Central

Riley, R. D.; Price, M. J.; Jackson, D.; Wardle, M.; Gueyffier, F.; Wang, J.; Staessen, J. A.; White, I. R.

2016-01-01

When combining results across related studies, a multivariate meta-analysis allows the joint synthesis of correlated effect estimates from multiple outcomes. Joint synthesis can improve efficiency over separate univariate syntheses, may reduce selective outcome reporting biases, and enables joint inferences across the outcomes. A common issue is that within-study correlations needed to fit the multivariate model are unknown from published reports. However, provision of individual participant data (IPD) allows them to be calculated directly. Here, we illustrate how to use IPD to estimate within-study correlations, using a joint linear regression for multiple continuous outcomes and bootstrapping methods for binary, survival and mixed outcomes. In a meta-analysis of 10 hypertension trials, we then show how these methods enable multivariate meta-analysis to address novel clinical questions about continuous, survival and binary outcomes; treatment–covariate interactions; adjusted risk/prognostic factor effects; longitudinal data; prognostic and multiparameter models; and multiple treatment comparisons. Both frequentist and Bayesian approaches are applied, with example software code provided to derive within-study correlations and to fit the models. PMID:26099484

Neural model of gene regulatory network: a survey on supportive meta-heuristics.

PubMed

Biswas, Surama; Acharyya, Sriyankar

2016-06-01

Gene regulatory network (GRN) is produced as a result of regulatory interactions between different genes through their coded proteins in cellular context. Having immense importance in disease detection and drug finding, GRN has been modelled through various mathematical and computational schemes and reported in survey articles. Neural and neuro-fuzzy models have been the focus of attraction in bioinformatics. Predominant use of meta-heuristic algorithms in training neural models has proved its excellence. Considering these facts, this paper is organized to survey neural modelling schemes of GRN and the efficacy of meta-heuristic algorithms towards parameter learning (i.e. weighting connections) within the model. This survey paper renders two different structure-related approaches to infer GRN which are global structure approach and substructure approach. It also describes two neural modelling schemes, such as artificial neural network/recurrent neural network based modelling and neuro-fuzzy modelling. The meta-heuristic algorithms applied so far to learn the structure and parameters of neutrally modelled GRN have been reviewed here.

Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis

PubMed Central

2011-01-01

Background Cochrane systematic reviews collate and summarise studies of the effects of healthcare interventions. The characteristics of these reviews and the meta-analyses and individual studies they contain provide insights into the nature of healthcare research and important context for the development of relevant statistical and other methods. Methods We classified every meta-analysis with at least two studies in every review in the January 2008 issue of the Cochrane Database of Systematic Reviews (CDSR) according to the medical specialty, the types of interventions being compared and the type of outcome. We provide descriptive statistics for numbers of meta-analyses, numbers of component studies and sample sizes of component studies, broken down by these categories. Results We included 2321 reviews containing 22,453 meta-analyses, which themselves consist of data from 112,600 individual studies (which may appear in more than one meta-analysis). Meta-analyses in the areas of gynaecology, pregnancy and childbirth (21%), mental health (13%) and respiratory diseases (13%) are well represented in the CDSR. Most meta-analyses address drugs, either with a control or placebo group (37%) or in a comparison with another drug (25%). The median number of meta-analyses per review is six (inter-quartile range 3 to 12). The median number of studies included in the meta-analyses with at least two studies is three (inter-quartile range 2 to 6). Sample sizes of individual studies range from 2 to 1,242,071, with a median of 91 participants. Discussion It is clear that the numbers of studies eligible for meta-analyses are typically very small for all medical areas, outcomes and interventions covered by Cochrane reviews. This highlights the particular importance of suitable methods for the meta-analysis of small data sets. There was little variation in number of studies per meta-analysis across medical areas, across outcome data types or across types of interventions being compared. PMID:22114982

Mobile Phone Apps to Promote Weight Loss and Increase Physical Activity: A Systematic Review and Meta-Analysis

PubMed Central

Ferré-Grau, Carme; Montaña-Carreras, Xavier

2015-01-01

Background To our knowledge, no meta-analysis to date has assessed the efficacy of mobile phone apps to promote weight loss and increase physical activity. Objective To perform a systematic review and meta-analysis of studies to compare the efficacy of mobile phone apps compared with other approaches to promote weight loss and increase physical activity. Methods We conducted a systematic review and meta-analysis of relevant studies identified by a search of PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus from their inception through to August 2015. Two members of the study team (EG-F, GF-M) independently screened studies for inclusion criteria and extracted data. We included all controlled studies that assessed a mobile phone app intervention with weight-related health measures (ie, body weight, body mass index, or waist circumference) or physical activity outcomes. Net change estimates comparing the intervention group with the control group were pooled across studies using random-effects models. Results We included 12 articles in this systematic review and meta-analysis. Compared with the control group, use of a mobile phone app was associated with significant changes in body weight (kg) and body mass index (kg/m2) of -1.04 kg (95% CI -1.75 to -0.34; I2 = 41%) and -0.43 kg/m2 (95% CI -0.74 to -0.13; I2 = 50%), respectively. Moreover, a nonsignificant difference in physical activity was observed between the two groups (standardized mean difference 0.40, 95% CI -0.07 to 0.87; I2 = 93%). These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. Conclusions Evidence from this study shows that mobile phone app-based interventions may be useful tools for weight loss. PMID:26554314

Bayesian Network Meta-Analysis for Unordered Categorical Outcomes with Incomplete Data

ERIC Educational Resources Information Center

Schmid, Christopher H.; Trikalinos, Thomas A.; Olkin, Ingram

2014-01-01

We develop a Bayesian multinomial network meta-analysis model for unordered (nominal) categorical outcomes that allows for partially observed data in which exact event counts may not be known for each category. This model properly accounts for correlations of counts in mutually exclusive categories and enables proper comparison and ranking of…

Video Modeling for Children and Adolescents with Autism Spectrum Disorder: A Meta-Analysis

ERIC Educational Resources Information Center

Thompson, Teresa Lynn

2014-01-01

The objective of this research was to conduct a meta-analysis to examine existing research studies on video modeling as an effective teaching tool for children and adolescents diagnosed with Autism Spectrum Disorder (ASD). Study eligibility criteria included (a) single case research design using multiple baselines, alternating treatment designs,…

Carbohydrate intake, obesity, metabolic syndrome and cancer risk? A two-part systematic review and meta-analysis protocol to estimate attributability

PubMed Central

Sartorius, B; Sartorius, K; Aldous, C; Madiba, T E; Stefan, C; Noakes, T

2016-01-01

Introduction Linkages between carbohydrates, obesity and cancer continue to demonstrate conflicting results. Evidence suggests inconclusive direct linkages between carbohydrates and specific cancers. Conversely, obesity has been strongly linked to a wide range of cancers. The purpose of the study is to explore linkages between carbohydrate intake and cancer types using a two-step approach. First the study will evaluate the linkages between carbohydrate intake and obesity, potentially stratified by metabolic syndrome status. Second, the estimated attributable fraction of obesity ascribed to carbohydrate intake will be multiplied against obesity attributable fractions for cancer types to give estimated overall attributable fraction for carbohydrate versus cancer type. Methods and analysis We will perform a comprehensive search to identify all possible published and unpublished studies that have assessed risk factors for obesity including dietary carbohydrate intake. Scientific databases, namely PubMed MEDLINE, EMBASE, EBSCOhost and ISI Web of Science will be searched. Following study selection, paper/data acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, as well as assess heterogeneity. Meta-weighted attributable fractions of obesity due to carbohydrate intake will be estimated after adjusting for other potential confounding factors (eg, physical inactivity, other dietary intake). Furthermore, previously published systematic reviews assessing the cancer-specific risk associated with obesity will also be drawn. These estimates will be linked with the attributability of carbohydrate intake in part 1 to estimate the cancer-specific burden that can be attributed to dietary carbohydrates. This systematic review protocol has been developed according to the ‘Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015’. Ethics and dissemination The current study will be based on published literature and data, and, as such, ethics approval is not required. The final results of this two part systematic review (plus multiplicative calculations) will be published in a relevant international peer-reviewed journal. Trial registration number PROSPERO CRD42015023257. PMID:26729382

Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

PubMed

Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

2012-09-01

There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested significant associations between ACE I/D, AGT M235T and PIH in Chinese populations. However, no significant association was found between ACE I/D and PIH in the subgroup of more than 100 cases. Studies with larger sample sizes are necessary to investigate the associations between gene polymorphisms and PIH in Chinese populations.

Task modulated brain connectivity of the amygdala: a meta-analysis of psychophysiological interactions.

PubMed

Di, Xin; Huang, Jia; Biswal, Bharat B

2017-01-01

Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta-analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity.

Prevalence of hepatitis C virus infection among high-risk groups in Iran: a systematic review and meta-analysis.

PubMed

Nematollahi, S; Ayubi, E; Almasi-Hashiani, A; Mansori, K; Moradi, Y; Veisani, Y; Jenabi, E; Gholamaliei, B; Khazaei, S

2018-06-20

Determination of the true burden of hepatitis C virus (HCV) infection among high-risk groups relies heavily on occurrence measures such as prevalence, which are vital for implementation of preventive action plans. Nevertheless, up-to-date data on the prevalence of HCV infection remain scarce in Iran. This study aimed to review the relevant literature systematically and determine the pooled prevalence of HCV infection among high-risk groups in Iran. Systematic review & meta-analysis. In 2016, electronic scientific databases including PubMed, Scopus, Web of Science and local databases were searched using a detailed search strategy with language restricted to English and Farsi. The reference lists of the studies included in this review were also screened. Data were reviewed and extracted independently by two authors. A random effects model was used to estimate the pooled prevalence. Sources of heterogeneity among the studies were determined using subgroup analysis and meta-regression. In total, 1817 records were identified in the initial search, and 46 records were included in the meta-analysis. The overall prevalence of HCV among high-risk groups was 32.3%. The prevalence was 41.3% in injection drug users (IDUs), 22.9% in prisoners, 16.2% in drug-dependent individuals and 24.6% in drug-dependent prisoners. Subgroup and meta-regression analyses revealed that geographical location and year of publication were the probable sources of heterogeneity. This meta-analysis found a high prevalence of HCV among high-risk groups in Iran, particularly among IDUs. There is a need for prevention strategies to reduce the burden of HCV infection among high-risk groups, particularly IDUs. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Serban, Corina; Sahebkar, Amirhossein; Ursoniu, Sorin; Andrica, Florina; Banach, Maciej

2015-06-01

Hibiscus sabdariffa L. is a tropical wild plant rich in organic acids, polyphenols, anthocyanins, polysaccharides, and volatile constituents that are beneficial for the cardiovascular system. Hibiscus sabdariffa beverages are commonly consumed to treat arterial hypertension, yet the evidence from randomized controlled trials (RCTs) has not been fully conclusive. Therefore, we aimed to assess the potential antihypertensive effects of H. sabdariffa through systematic review of literature and meta-analysis of available RCTs. The search included PUBMED, Cochrane Library, Scopus, and EMBASE (up to July 2014) to identify RCTs investigating the efficacy of H. sabdariffa supplementation on SBP and DBP values. Two independent reviewers extracted data on the study characteristics, methods, and outcomes. Quantitative data synthesis and meta-regression were performed using a fixed-effect model, and sensitivity analysis using leave-one-out method. Five RCTs (comprising seven treatment arms) were selected for the meta-analysis. In total, 390 participants were randomized, of whom 225 were allocated to the H. sabdariffa supplementation group and 165 to the control group in the selected studies. Fixed-effect meta-regression indicated a significant effect of H. sabdariffa supplementation in lowering both SBP (weighed mean difference -7.58 mmHg, 95% confidence interval -9.69 to -5.46, P < 0.00001) and DBP (weighed mean difference -3.53 mmHg, 95% confidence interval -5.16 to -1.89, P < 0.0001). These effects were inversely associated with baseline BP values, and were robust in sensitivity analyses. This meta-analysis of RCTs showed a significant effect of H. sabdariffa in lowering both SBP and DBP. Further well designed trials are necessary to validate these results.

Efficacy of rasagiline in early Parkinson's disease: a meta-analysis of data from the TEMPO and ADAGIO studies.

PubMed

Hauser, Robert A; Abler, Victor; Eyal, Eli; Eliaz, Rom E

2016-10-01

To evaluate the efficacy of rasagiline versus placebo in a pooled population of patients with early Parkinson's disease (PD). TEMPO and ADAGIO were Phase III studies that evaluated the symptomatic efficacy of rasagiline versus placebo in patients with early PD. This meta-analysis included Unified Parkinson's Disease Rating Scale (UPDRS) observations from weeks 12, 24 and 36 in ADAGIO and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded to weeks 12 and 24, respectively. The present analysis includes all patients who received rasagiline 1 mg/day, 2 mg/day or placebo, and had ≥1 post-baseline observations and a subgroup of patients whose baseline UPDRS Total scores were ≥27 (Upper Quartile population). Change from baseline in UPDRS scores were evaluated using mixed models repeated measures analyses. Of the 1578 patients randomized to the two studies, 1546 patients met criteria for inclusion in the meta-analysis. Effects on UPDRS Total, motor and activities of daily living scores were significantly better for both doses of rasagiline compared with placebo at all time periods. The Upper Quartile population included 402 patients with a UPDRS Total score ≥27 at baseline. These patients generally demonstrated a larger magnitude of treatment effect than was seen in the full population. This meta-analysis confirms the efficacy of rasagiline monotherapy over 36 weeks. Although TEMPO and ADAGIO are considered studies of "very early" PD, both contained a sizeable pool of patients with more severe disease. In addition, the meta-analysis showed a larger magnitude of effect in patients with more severe baseline disease.

Effectiveness of problem-based learning in Chinese dental education: a meta-analysis.

PubMed

Huang, Beilei; Zheng, Liwei; Li, Chunjie; Li, Li; Yu, Haiyang

2013-03-01

This article provides a critical overview of problem-based learning (PBL) practice in dental education in China. Because the application of PBL has not been carried out on a large scale in Chinese dental education, this review was performed to investigate its effectiveness. Databases were searched for studies that met the inclusion criteria, with study identification and data extraction performed by two reviewers independently. Meta-analysis was done with Revman 5.1. Eleven randomized controlled trials were included. The meta-analysis found that PBL had a positive effect on gaining higher theoretical (SMD=0.88, 95% CI [0.46, 1.31], p<0.0001) and practical scores (SMD=1.48, 95% CI [0.95, 2.00], p<0.0001). However, the pooled result did not show any positive effect on gaining higher pass rates (RR=1.06, 95% CI [0.97, 1.16], p=0.21). This meta-analysis suggests that the PBL pedagogy is considered superior to the traditional lecture-based teaching in this setting. PBL methods could be an optional supplementary method of dental teaching models in China. However, Chinese dental schools should devise PBL curricula according to their own conditions. The effectiveness of PBL should be optimized maximally with all these limitations.

Depression as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies.

PubMed

Gao, Yuan; Huang, Changquan; Zhao, Kexiang; Ma, Louyan; Qiu, Xuan; Zhang, Lei; Xiu, Yun; Chen, Lin; Lu, Wei; Huang, Chunxia; Tang, Yong; Xiao, Qian

2013-05-01

This study examined whether depression was a risk factor for onset of dementia including Alzheimer's disease (AD), vascular dementia (VD) and any dementia, and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to February 2011. All studies that examined the relationship between depression and the onset of dementia or MCI were included. Pooled relative risk was calculated using fixed-effects models. Twelve studies met our inclusion criteria for this meta-analysis. All subjects were without dementia or MCI at baseline. Four, two, five, and four studies compared the incidence of AD, VD, any dementia, and MCI between subjects with or without depression, respectively. After pooling all the studies, subjects with depression had higher incidence of AD (relative risk (RR):1.66, 95% confidence interval (CI): 1.29-2.14), VD (RR: 1.89, 95% CI: 1.19-3.01), any dementia (RR: 1.55, 95% CI: 1.31-2.83), and MCI (RR: 1.97, 95% CI: 1.53-2.54) than those without depression. The quantitative meta-analysis showed that depression was a major risk factor for incidence of dementia (including AD, VD, and any dementia) and MCI. Copyright © 2012 John Wiley & Sons, Ltd.

Prevalence of Enterobius vermicularis among Children in Iran: A Systematic Review and Meta-analysis

PubMed Central

Moosazadeh, Mahmood; Abedi, Ghasem; Afshari, Mahdi; Mahdavi, Seif Ali; Farshidi, Fereshteh; Kheradmand, Elham

2017-01-01

Objectives Enterobius vermicularis is a parasitic disease that is common in crowded areas such as schools and kindergartens. Primary investigations of electronic evidence have reported different prevalences of E. vermicularis in Iran. Therefore, we aimed to estimate the total prevalence of this infection among Iranian children using a meta-analysis. Methods Relevant studies were identified in national and international databases. We selected eligible papers for meta-analysis after investigating titles, abstracts, and full texts; assessing study quality; and applying inclusion/exclusion criteria. Data were extracted by two independent researchers. The results were combined using a random effects model in Stata v. 11 software. Results Among 19 eligible articles including 11,676 participants, the prevalences of E. vermicularis among all children, boys, and girls were 1.2%–66.1%, 2.3%–65.5%, and 1.7%–65.5%, respectively. Pooled prevalences (95% confidence interval) of E. vermicularis among all children, boys, and girls were 17.2% (12.6%–21.8%), 17.2% (12.6%–21.8%), and 16.9% (9.03%–24.8%), respectively. Conclusion This meta-analysis showed that a great majority of Iranian children are infected with E. vermicularis, possibly due to poor public health. PMID:28540154

Occupational exposure and risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

PubMed

Alif, Sheikh M; Dharmage, Shyamali C; Bowatte, Gayan; Karahalios, Amalia; Benke, Geza; Dennekamp, Martine; Mehta, Amar J; Miedinger, David; Künzli, Nino; Probst-Hensch, Nicole; Matheson, Melanie C

2016-08-01

Due to contradictory literature we have performed a systematic review and meta-analyse of population-based studies that have used Job Exposure Matrices to assess occupational exposure and risk of Chronic Obstructive Pulmonary Disease (COPD). Two researchers independently searched databases for published articles using predefined inclusion criteria. Study quality was assessed, and results pooled for COPD and chronic bronchitis for exposure to biological dust, mineral dust, and gases/fumes using a fixed and random effect model. Five studies met predetermined inclusion criteria. The meta-analysis showed low exposure to mineral dust, and high exposure to gases/fumes were associated with an increased risk of COPD. We also found significantly increased the risk of chronic bronchitis for low and high exposure to biological dust and mineral dust. Expert commentary: The relationship between occupational exposure assessed by the JEM and the risk of COPD and chronic bronchitis shows significant association with occupational exposure. However, the heterogeneity of the meta-analyses suggests more wide population-based studies with older age groups and longitudinal phenotype assessment of COPD to clarify the role of occupational exposure to COPD risk.

Meta-Analysis inside and outside Particle Physics: Two Traditions That Should Converge?

ERIC Educational Resources Information Center

Baker, Rose D.; Jackson, Dan

2013-01-01

The use of meta-analysis in medicine and epidemiology really took off in the 1970s. However, in high-energy physics, the Particle Data Group has been carrying out meta-analyses of measurements of particle masses and other properties since 1957. Curiously, there has been virtually no interaction between those working inside and outside particle…

Meta-analysis suggests choosy females get sexy sons more than "good genes".

PubMed

Prokop, Zofia M; Michalczyk, Łukasz; Drobniak, Szymon M; Herdegen, Magdalena; Radwan, Jacek

2012-09-01

Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Guideline validation in multiple trauma care through business process modeling.

PubMed

Stausberg, Jürgen; Bilir, Hüseyin; Waydhas, Christian; Ruchholtz, Steffen

2003-07-01

Clinical guidelines can improve the quality of care in multiple trauma. In our Department of Trauma Surgery a specific guideline is available paper-based as a set of flowcharts. This format is appropriate for the use by experienced physicians but insufficient for electronic support of learning, workflow and process optimization. A formal and logically consistent version represented with a standardized meta-model is necessary for automatic processing. In our project we transferred the paper-based into an electronic format and analyzed the structure with respect to formal errors. Several errors were detected in seven error categories. The errors were corrected to reach a formally and logically consistent process model. In a second step the clinical content of the guideline was revised interactively using a process-modeling tool. Our study reveals that guideline development should be assisted by process modeling tools, which check the content in comparison to a meta-model. The meta-model itself could support the domain experts in formulating their knowledge systematically. To assure sustainability of guideline development a representation independent of specific applications or specific provider is necessary. Then, clinical guidelines could be used for eLearning, process optimization and workflow management additionally.

Meta-analysis using Dirichlet process.

PubMed

Muthukumarana, Saman; Tiwari, Ram C

2016-02-01

This article develops a Bayesian approach for meta-analysis using the Dirichlet process. The key aspect of the Dirichlet process in meta-analysis is the ability to assess evidence of statistical heterogeneity or variation in the underlying effects across study while relaxing the distributional assumptions. We assume that the study effects are generated from a Dirichlet process. Under a Dirichlet process model, the study effects parameters have support on a discrete space and enable borrowing of information across studies while facilitating clustering among studies. We illustrate the proposed method by applying it to a dataset on the Program for International Student Assessment on 30 countries. Results from the data analysis, simulation studies, and the log pseudo-marginal likelihood model selection procedure indicate that the Dirichlet process model performs better than conventional alternative methods. © The Author(s) 2012.

Current collapse in tunneling transport through benzene.

PubMed

Hettler, M H; Wenzel, W; Wegewijs, M R; Schoeller, H

2003-02-21

We investigate the electrical transport through a system of benzene coupled to metal electrodes by electron tunneling. Using electronic structure calculations, a semiquantitative model for the pi electrons of the benzene is derived that includes general two-body interactions. After exact diagonalization of the benzene model the transport is computed using perturbation theory for weak electrode-benzene coupling (golden rule approximation). We include the effect of an applied electric field on the molecular states, as well as radiative relaxation. We predict a current collapse and strong negative differential conductance due to a "blocking" state when the electrode is coupled to the para-position of benzene. In contrast, for coupling to the meta-position, a series of steps in the I-V curve is found.

Meta-analysis of thirty-two case-control and two ecological radon studies of lung cancer.

PubMed

Dobrzynski, Ludwik; Fornalski, Krzysztof W; Reszczynska, Joanna

2018-03-01

A re-analysis has been carried out of thirty-two case-control and two ecological studies concerning the influence of radon, a radioactive gas, on the risk of lung cancer. Three mathematically simplest dose-response relationships (models) were tested: constant (zero health effect), linear, and parabolic (linear-quadratic). Health effect end-points reported in the analysed studies are odds ratios or relative risk ratios, related either to morbidity or mortality. In our preliminary analysis, we show that the results of dose-response fitting are qualitatively (within uncertainties, given as error bars) the same, whichever of these health effect end-points are applied. Therefore, we deemed it reasonable to aggregate all response data into the so-called Relative Health Factor and jointly analysed such mixed data, to obtain better statistical power. In the second part of our analysis, robust Bayesian and classical methods of analysis were applied to this combined dataset. In this part of our analysis, we selected different subranges of radon concentrations. In view of substantial differences between the methodology used by the authors of case-control and ecological studies, the mathematical relationships (models) were applied mainly to the thirty-two case-control studies. The degree to which the two ecological studies, analysed separately, affect the overall results when combined with the thirty-two case-control studies, has also been evaluated. In all, as a result of our meta-analysis of the combined cohort, we conclude that the analysed data concerning radon concentrations below ~1000 Bq/m3 (~20 mSv/year of effective dose to the whole body) do not support the thesis that radon may be a cause of any statistically significant increase in lung cancer incidence.

Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder.

PubMed

Navarro-Mateu, Fernando; Escámez, Teresa; Koenen, Karestan C; Alonso, Jordi; Sánchez-Meca, Julio

2013-01-01

To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases. Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011. Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. A biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2) index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed. 13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias. Current evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.

Competence and Performance in Belief-Desire Reasoning across Two Cultures: The Truth, the Whole Truth and Nothing but the Truth about False Belief?

ERIC Educational Resources Information Center

Yazdi, Amir Amin; German, Tim P.; Defeyter, Margaret Anne; Siegal, Michael

2006-01-01

There is a change in false belief task performance across the 3-5 year age range, as confirmed in a recent meta-analysis [Wellman, H. M., Cross, D., & Watson, J. (2001). Meta-analysis of theory mind development: The truth about false-belief. "Child Development," 72, 655-684]. This meta-analysis identified several performance factors influencing…

Meta-shell Approach for Constructing Lightweight and High Resolution X-Ray Optics

NASA Technical Reports Server (NTRS)

McClelland, Ryan S.

2016-01-01

Lightweight and high resolution optics are needed for future space-based x-ray telescopes to achieve advances in high-energy astrophysics. Past missions such as Chandra and XMM-Newton have achieved excellent angular resolution using a full shell mirror approach. Other missions such as Suzaku and NuSTAR have achieved lightweight mirrors using a segmented approach. This paper describes a new approach, called meta-shells, which combines the fabrication advantages of segmented optics with the alignment advantages of full shell optics. Meta-shells are built by layering overlapping mirror segments onto a central structural shell. The resulting optic has the stiffness and rotational symmetry of a full shell, but with an order of magnitude greater collecting area. Several meta-shells so constructed can be integrated into a large x-ray mirror assembly by proven methods used for Chandra and XMM-Newton. The mirror segments are mounted to the meta-shell using a novel four point semi-kinematic mount. The four point mount deterministically locates the segment in its most performance sensitive degrees of freedom. Extensive analysis has been performed to demonstrate the feasibility of the four point mount and meta-shell approach. A mathematical model of a meta-shell constructed with mirror segments bonded at four points and subject to launch loads has been developed to determine the optimal design parameters, namely bond size, mirror segment span, and number of layers per meta-shell. The parameters of an example 1.3 m diameter mirror assembly are given including the predicted effective area. To verify the mathematical model and support opto-mechanical analysis, a detailed finite element model of a meta-shell was created. Finite element analysis predicts low gravity distortion and low thermal distortion. Recent results are discussed including Structural Thermal Optical Performance (STOP) analysis as well as vibration and shock testing of prototype meta-shells.

Publication bias in obesity treatment trials?

PubMed

Allison, D B; Faith, M S; Gorman, B S

1996-10-01

The present investigation examined the extent of publication bias (namely the tendency to publish significant findings and file away non-significant findings) within the obesity treatment literature. Quantitative literature synthesis of four published meta-analyses from the obesity treatment literature. Interventions in these studies included pharmacological, educational, child, and couples treatments. To assess publication bias, several regression procedures (for example weighted least-squares, random-effects multi-level modeling, and robust regression methods) were used to regress effect sizes onto their standard errors, or proxies thereof, within each of the four meta-analysis. A significant positive beta weight in these analyses signified publication bias. There was evidence for publication bias within two of the four published meta-analyses, such that reviews of published studies were likely to overestimate clinical efficacy. The lack of evidence for publication bias within the two other meta-analyses might have been due to insufficient statistical power rather than the absence of selection bias. As in other disciplines, publication bias appears to exist in the obesity treatment literature. Suggestions are offered for managing publication bias once identified or reducing its likelihood in the first place.

The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-Analysis Revisited: Evidence of Genetic Moderation

PubMed Central

Karg, Katja; Burmeister, Margit; Shedden, Kerby; Sen, Srijan

2013-01-01

Context The initial report of an interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and stress in the development of depression is perhaps the best-known and most cited finding in psychiatric genetics. Two recent meta-analyses explored the studies seeking to replicate this initial report and concluded that the evidence did not support the presence of the interaction. However, even the larger of the meta-analyses included only 14 of the 56 studies that have explored the relationship between 5-HTTLPR, stress and depression. Objective We sought to perform a meta-analysis including all relevant studies assessing whether 5-HTTLPR moderates the relationship between stress and depression. Data Sources We identified relevant articles from previous meta-analyses and reviews and a PubMed database search. Study Selection We excluded two studies presenting data that were included in other, larger, studies already included in our meta-analysis to avoid duplicate counting of subjects. Data Extraction In order to perform a more inclusive meta-analysis, we used the Liptak-Stouffer Z-score method to combine findings of primary studies at the significance test level rather than raw data level. Results We included 54 studies and found strong evidence that 5-HTTLPR moderates the relationship between stress and depression, with the 5-HTTLPR s allele associated with an increased risk of developing depression under stress (p<0.0001). When restricting our analysis to the studies included in the previous meta-analyses, we found no evidence of association (Munafo studies p=0.16; Risch studies p=0.11). This suggests that the difference in results between previous meta-analyses and ours was not due to the difference in meta-analytic technique but instead to the expanded set of studies included in this analysis. Conclusions Contrary to the results of the smaller earlier meta-analyses, we find strong evidence that 5-HTTLPR moderates the relationship between stress and depression in the studies published to date. PMID:21199959

The more total cognitive load is reduced by cues, the better retention and transfer of multimedia learning: A meta-analysis and two meta-regression analyses.

PubMed

Xie, Heping; Wang, Fuxing; Hao, Yanbin; Chen, Jiaxue; An, Jing; Wang, Yuxin; Liu, Huashan

2017-01-01

Cueing facilitates retention and transfer of multimedia learning. From the perspective of cognitive load theory (CLT), cueing has a positive effect on learning outcomes because of the reduction in total cognitive load and avoidance of cognitive overload. However, this has not been systematically evaluated. Moreover, what remains ambiguous is the direct relationship between the cue-related cognitive load and learning outcomes. A meta-analysis and two subsequent meta-regression analyses were conducted to explore these issues. Subjective total cognitive load (SCL) and scores on a retention test and transfer test were selected as dependent variables. Through a systematic literature search, 32 eligible articles encompassing 3,597 participants were included in the SCL-related meta-analysis. Among them, 25 articles containing 2,910 participants were included in the retention-related meta-analysis and the following retention-related meta-regression, while there were 29 articles containing 3,204 participants included in the transfer-related meta-analysis and the transfer-related meta-regression. The meta-analysis revealed a statistically significant cueing effect on subjective ratings of cognitive load (d = -0.11, 95% CI = [-0.19, -0.02], p < 0.05), retention performance (d = 0.27, 95% CI = [0.08, 0.46], p < 0.01), and transfer performance (d = 0.34, 95% CI = [0.12, 0.56], p < 0.01). The subsequent meta-regression analyses showed that dSCL for cueing significantly predicted dretention for cueing (β = -0.70, 95% CI = [-1.02, -0.38], p < 0.001), as well as dtransfer for cueing (β = -0.60, 95% CI = [-0.92, -0.28], p < 0.001). Thus in line with CLT, adding cues in multimedia materials can indeed reduce SCL and promote learning outcomes, and the more SCL is reduced by cues, the better retention and transfer of multimedia learning.

The more total cognitive load is reduced by cues, the better retention and transfer of multimedia learning: A meta-analysis and two meta-regression analyses

PubMed Central

Hao, Yanbin; Chen, Jiaxue; An, Jing; Wang, Yuxin; Liu, Huashan

2017-01-01

Cueing facilitates retention and transfer of multimedia learning. From the perspective of cognitive load theory (CLT), cueing has a positive effect on learning outcomes because of the reduction in total cognitive load and avoidance of cognitive overload. However, this has not been systematically evaluated. Moreover, what remains ambiguous is the direct relationship between the cue-related cognitive load and learning outcomes. A meta-analysis and two subsequent meta-regression analyses were conducted to explore these issues. Subjective total cognitive load (SCL) and scores on a retention test and transfer test were selected as dependent variables. Through a systematic literature search, 32 eligible articles encompassing 3,597 participants were included in the SCL-related meta-analysis. Among them, 25 articles containing 2,910 participants were included in the retention-related meta-analysis and the following retention-related meta-regression, while there were 29 articles containing 3,204 participants included in the transfer-related meta-analysis and the transfer-related meta-regression. The meta-analysis revealed a statistically significant cueing effect on subjective ratings of cognitive load (d = −0.11, 95% CI = [−0.19, −0.02], p < 0.05), retention performance (d = 0.27, 95% CI = [0.08, 0.46], p < 0.01), and transfer performance (d = 0.34, 95% CI = [0.12, 0.56], p < 0.01). The subsequent meta-regression analyses showed that dSCL for cueing significantly predicted dretention for cueing (β = −0.70, 95% CI = [−1.02, −0.38], p < 0.001), as well as dtransfer for cueing (β = −0.60, 95% CI = [−0.92, −0.28], p < 0.001). Thus in line with CLT, adding cues in multimedia materials can indeed reduce SCL and promote learning outcomes, and the more SCL is reduced by cues, the better retention and transfer of multimedia learning. PMID:28854205

Incidence of urinary extravasation and rate of ureteral stenting after high-grade renal trauma in adults: a meta-analysis

PubMed Central

Anderson, Ross E.; Fiander, Michelle; McFarland, Mary M.; Stoddard, Gregory J.; Hotaling, James M.; Myers, Jeremy B.

2018-01-01

Background Collecting system injury and urinary extravasation is an important yet understudied aspect of renal trauma. We aimed to examine the incidence of urinary extravasation and also the rates of ureteral stenting after high-grade renal trauma (HGRT) in adults. Methods A search strategy was developed to search Ovid Medline, Embase, CINAHL, and Cochrane Library. Two reviewers screened titles and abstracts, followed by full-text review of the relevant publications. Studies were included if they indicated the number of patients with HGRT [the American Association for the Surgery of Trauma (AAST) grades III–IV or equivalents] and number of patients with urinary extravasation. A descriptive meta-analysis of binary proportions was performed with random-effects model to calculate the incidence of urinary extravasation and rates of ureteral stenting. Results After screening, 24 and 20 studies were included for calculating urinary extravasation and stenting rates, respectively. Most studies involved blunt injury and were retrospective single-center case series. Incidence of urinary extravasation was 29% (95% CI: 17–42%) after HGRT (grade III–V), and 51% (95% CI: 38–64%) when only grade IV–V injuries were combined. Overall, 29% (95% CI: 22–36%) of patients with urinary extravasation underwent ureteral stenting. Conclusions Approximately 30% of patients with HGRT are diagnosed with urinary extravasation and 29% of those with urinary extravasation undergo ureteral stenting. Understanding the rate of urinary extravasation and interventions is the first step in creating a prospective trial designed to demonstrate when ureteral stenting and aggressive management of urinary extravasation is needed. PMID:29928614

Incidence of urinary extravasation and rate of ureteral stenting after high-grade renal trauma in adults: a meta-analysis.

PubMed

Keihani, Sorena; Anderson, Ross E; Fiander, Michelle; McFarland, Mary M; Stoddard, Gregory J; Hotaling, James M; Myers, Jeremy B

2018-05-01

Collecting system injury and urinary extravasation is an important yet understudied aspect of renal trauma. We aimed to examine the incidence of urinary extravasation and also the rates of ureteral stenting after high-grade renal trauma (HGRT) in adults. A search strategy was developed to search Ovid Medline, Embase, CINAHL, and Cochrane Library. Two reviewers screened titles and abstracts, followed by full-text review of the relevant publications. Studies were included if they indicated the number of patients with HGRT [the American Association for the Surgery of Trauma (AAST) grades III-IV or equivalents] and number of patients with urinary extravasation. A descriptive meta-analysis of binary proportions was performed with random-effects model to calculate the incidence of urinary extravasation and rates of ureteral stenting. After screening, 24 and 20 studies were included for calculating urinary extravasation and stenting rates, respectively. Most studies involved blunt injury and were retrospective single-center case series. Incidence of urinary extravasation was 29% (95% CI: 17-42%) after HGRT (grade III-V), and 51% (95% CI: 38-64%) when only grade IV-V injuries were combined. Overall, 29% (95% CI: 22-36%) of patients with urinary extravasation underwent ureteral stenting. Approximately 30% of patients with HGRT are diagnosed with urinary extravasation and 29% of those with urinary extravasation undergo ureteral stenting. Understanding the rate of urinary extravasation and interventions is the first step in creating a prospective trial designed to demonstrate when ureteral stenting and aggressive management of urinary extravasation is needed.

Meta-analysis genomewide association of pork quality traits: ultimate pH and shear force

USDA-ARS?s Scientific Manuscript database

It is common practice to perform genome-wide association analysis (GWA) using a genomic evaluation model of a single population. Joint analysis of several populations is more difficult. An alternative to joint analysis could be the meta-analysis (MA) of several GWA from independent genomic evaluatio...

The role of environmental heterogeneity in meta-analysis of gene-environment interactions with quantitative traits.

PubMed

Li, Shi; Mukherjee, Bhramar; Taylor, Jeremy M G; Rice, Kenneth M; Wen, Xiaoquan; Rice, John D; Stringham, Heather M; Boehnke, Michael

2014-07-01

With challenges in data harmonization and environmental heterogeneity across various data sources, meta-analysis of gene-environment interaction studies can often involve subtle statistical issues. In this paper, we study the effect of environmental covariate heterogeneity (within and between cohorts) on two approaches for fixed-effect meta-analysis: the standard inverse-variance weighted meta-analysis and a meta-regression approach. Akin to the results in Simmonds and Higgins (), we obtain analytic efficiency results for both methods under certain assumptions. The relative efficiency of the two methods depends on the ratio of within versus between cohort variability of the environmental covariate. We propose to use an adaptively weighted estimator (AWE), between meta-analysis and meta-regression, for the interaction parameter. The AWE retains full efficiency of the joint analysis using individual level data under certain natural assumptions. Lin and Zeng (2010a, b) showed that a multivariate inverse-variance weighted estimator retains full efficiency as joint analysis using individual level data, if the estimates with full covariance matrices for all the common parameters are pooled across all studies. We show consistency of our work with Lin and Zeng (2010a, b). Without sacrificing much efficiency, the AWE uses only univariate summary statistics from each study, and bypasses issues with sharing individual level data or full covariance matrices across studies. We compare the performance of the methods both analytically and numerically. The methods are illustrated through meta-analysis of interaction between Single Nucleotide Polymorphisms in FTO gene and body mass index on high-density lipoprotein cholesterol data from a set of eight studies of type 2 diabetes. © 2014 WILEY PERIODICALS, INC.

Assessing Independent Variables Used in Econometric Modeling Forest Land Use or Land Cover Change: A Meta-Analysis

Treesearch

J Jeuck; F. Cubbage; R. Abt; R. Bardon; J. McCarter; J. Coulston; M. Renkow

2014-01-01

: We conducted a meta-analysis on 64 econometric models from 47 studies predicting forestland conversion to agriculture (F2A), forestland to development (F2D), forestland to non-forested (F2NF) and undeveloped (including forestland) to developed (U2D) land. Over 250 independent econometric variables were identified from 21 F2A models, 21 F2D models, 12 F2NF models, and...

A Methodology for Meta-Analysis of Local Climate Change Adaptation Policies

EPA Science Inventory

Local governments are beginning to take steps to address the consequences of climate change, such as sea level rise and heat events. However, we donot have a clear understanding of what local governments are doing -- the extent to which they expect climate change to affect their ...

A Meta-Analysis of Local Climate Change Adaptation Actions

EPA Science Inventory

Local governments are beginning to take steps to address the consequences of climate change, such as sea level rise and heat events. However, we do not have a clear understanding of what local governments are doing -- the extent to which they expect climate change to affect their...

Computer-Assisted Second Language Vocabulary Instruction: A Meta-Analysis

ERIC Educational Resources Information Center

Chiu, Yi-Hui

2013-01-01

There is growing attention to incorporating computer-mediated instruction for language learning and teaching. Specifically, vocabulary is arguably the foundation of mastering a language, as the mastery of vocabulary is the fundamental step of learning a language. Second language (L2) vocabulary is important in the development of cognitive systems…

Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

PubMed

Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

2017-06-01

We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficiency enhancement of optimized Latin hypercube sampling strategies: Application to Monte Carlo uncertainty analysis and meta-modeling

NASA Astrophysics Data System (ADS)

Rajabi, Mohammad Mahdi; Ataie-Ashtiani, Behzad; Janssen, Hans

2015-02-01

The majority of literature regarding optimized Latin hypercube sampling (OLHS) is devoted to increasing the efficiency of these sampling strategies through the development of new algorithms based on the combination of innovative space-filling criteria and specialized optimization schemes. However, little attention has been given to the impact of the initial design that is fed into the optimization algorithm, on the efficiency of OLHS strategies. Previous studies, as well as codes developed for OLHS, have relied on one of the following two approaches for the selection of the initial design in OLHS: (1) the use of random points in the hypercube intervals (random LHS), and (2) the use of midpoints in the hypercube intervals (midpoint LHS). Both approaches have been extensively used, but no attempt has been previously made to compare the efficiency and robustness of their resulting sample designs. In this study we compare the two approaches and show that the space-filling characteristics of OLHS designs are sensitive to the initial design that is fed into the optimization algorithm. It is also illustrated that the space-filling characteristics of OLHS designs based on midpoint LHS are significantly better those based on random LHS. The two approaches are compared by incorporating their resulting sample designs in Monte Carlo simulation (MCS) for uncertainty propagation analysis, and then, by employing the sample designs in the selection of the training set for constructing non-intrusive polynomial chaos expansion (NIPCE) meta-models which subsequently replace the original full model in MCSs. The analysis is based on two case studies involving numerical simulation of density dependent flow and solute transport in porous media within the context of seawater intrusion in coastal aquifers. We show that the use of midpoint LHS as the initial design increases the efficiency and robustness of the resulting MCSs and NIPCE meta-models. The study also illustrates that this relative improvement decreases with increasing number of sample points and input parameter dimensions. Since the computational time and efforts for generating the sample designs in the two approaches are identical, the use of midpoint LHS as the initial design in OLHS is thus recommended.

Metabolic network visualization eliminating node redundance and preserving metabolic pathways

PubMed Central

Bourqui, Romain; Cottret, Ludovic; Lacroix, Vincent; Auber, David; Mary, Patrick; Sagot, Marie-France; Jourdan, Fabien

2007-01-01

Background The tools that are available to draw and to manipulate the representations of metabolism are usually restricted to metabolic pathways. This limitation becomes problematic when studying processes that span several pathways. The various attempts that have been made to draw genome-scale metabolic networks are confronted with two shortcomings: 1- they do not use contextual information which leads to dense, hard to interpret drawings, 2- they impose to fit to very constrained standards, which implies, in particular, duplicating nodes making topological analysis considerably more difficult. Results We propose a method, called MetaViz, which enables to draw a genome-scale metabolic network and that also takes into account its structuration into pathways. This method consists in two steps: a clustering step which addresses the pathway overlapping problem and a drawing step which consists in drawing the clustered graph and each cluster. Conclusion The method we propose is original and addresses new drawing issues arising from the no-duplication constraint. We do not propose a single drawing but rather several alternative ways of presenting metabolism depending on the pathway on which one wishes to focus. We believe that this provides a valuable tool to explore the pathway structure of metabolism. PMID:17608928

Laser-Induced Translative Hydrodynamic Mass Snapshots: Noninvasive Characterization and Predictive Modeling via Mapping at Nanoscale

NASA Astrophysics Data System (ADS)

Wang, X. W.; Kuchmizhak, A. A.; Li, X.; Juodkazis, S.; Vitrik, O. B.; Kulchin, Yu. N.; Zhakhovsky, V. V.; Danilov, P. A.; Ionin, A. A.; Kudryashov, S. I.; Rudenko, A. A.; Inogamov, N. A.

2017-10-01

Subwavelength structures (meta-atoms) with artificially engineered permittivity and permeability have shown promising applications for guiding and controlling the flow of electromagnetic energy on the nanoscale. Ultrafast laser nanoprinting emerges as a promising single-step, green and flexible technology in fabricating large-area arrays of meta-atoms through the translative or ablative modification of noble-metal thin films. Ultrafast laser energy deposition in noble-metal films produces irreversible, intricate nanoscale translative mass redistributions after resolidification of the transient thermally assisted hydrodynamic melt perturbations. Such mass redistribution results in the formation of a radially symmetric frozen surface with modified hidden nanofeatures, which strongly affect the optical response harnessed in plasmonic sensing and nonlinear optical applications. Here, we demonstrate that side-view electron microscopy and ion-beam cross sections together with low-energy electron x-ray dispersion microscopy provide exact information about such three-dimensional patterns, enabling an accurate acquisition of their cross-sectional mass distributions. Such nanoscale solidified structures are theoretically modeled, considering the underlying physical processes associated with laser-induced energy absorption, electron-ion energy exchange, acoustic relaxation, and hydrodynamic flows. A theoretical approach, separating slow and fast physical processes and combining hybrid analytical two-temperature calculations, scalable molecular-dynamics simulations, and a semianalytical thin-shell model is synergistically applied. These advanced characterization approaches are required for a detailed modeling of near-field electromagnetic response and pave the way to a fully automated noninvasive in-line control of a high-throughput and large-scale laser fabrication. This theoretical modeling provides an accurate prediction of scales and topographies of the laser-fabricated meta-atoms and metasurfaces.

Short-term effects of air quality and thermal stress on non-accidental morbidity-a multivariate meta-analysis comparing indices to single measures.

PubMed

Lokys, Hanna Leona; Junk, Jürgen; Krein, Andreas

2018-01-01

Air quality and thermal stress lead to increased morbidity and mortality. Studies on morbidity and the combined impact of air pollution and thermal stress are still rare. To analyse the correlations between air quality, thermal stress and morbidity, we used a two-stage meta-analysis approach, consisting of a Poisson regression model combined with distributed lag non-linear models (DLNMs) and a meta-analysis investigating whether latitude or the number of inhabitants significantly influence the correlations. We used air pollution, meteorological and hospital admission data from 28 administrative districts along a north-south gradient in western Germany from 2001 to 2011. We compared the performance of the single measure particulate matter (PM10) and air temperature to air quality indices (MPI and CAQI) and the biometeorological index UTCI. Based on the Akaike information criterion (AIC), it can be shown that using air quality indices instead of single measures increases the model strength. However, using the UTCI in the model does not give additional information compared to mean air temperature. Interaction between the 3-day average of air quality (max PM10, max CAQI and max MPI) and meteorology (mean air temperature and mean UTCI) did not improve the models. Using the mean air temperature, we found immediate effects of heat stress (RR 1.0013, 95% CI: 0.9983-1.0043) and by 3 days delayed effects of cold stress (RR: 1.0184, 95% CI: 1.0117-1.0252). The results for air quality differ between both air quality indices and PM10. CAQI and MPI show a delayed impact on morbidity with a maximum RR after 2 days (MPI 1.0058, 95% CI: 1.0013-1.0102; CAQI 1.0068, 95% CI: 1.0030-1.0107). Latitude was identified as a significant meta-variable, whereas the number of inhabitants was not significant in the model.

Short-term effects of air quality and thermal stress on non-accidental morbidity—a multivariate meta-analysis comparing indices to single measures

NASA Astrophysics Data System (ADS)

Lokys, Hanna Leona; Junk, Jürgen; Krein, Andreas

2018-01-01

Air quality and thermal stress lead to increased morbidity and mortality. Studies on morbidity and the combined impact of air pollution and thermal stress are still rare. To analyse the correlations between air quality, thermal stress and morbidity, we used a two-stage meta-analysis approach, consisting of a Poisson regression model combined with distributed lag non-linear models (DLNMs) and a meta-analysis investigating whether latitude or the number of inhabitants significantly influence the correlations. We used air pollution, meteorological and hospital admission data from 28 administrative districts along a north-south gradient in western Germany from 2001 to 2011. We compared the performance of the single measure particulate matter (PM10) and air temperature to air quality indices (MPI and CAQI) and the biometeorological index UTCI. Based on the Akaike information criterion (AIC), it can be shown that using air quality indices instead of single measures increases the model strength. However, using the UTCI in the model does not give additional information compared to mean air temperature. Interaction between the 3-day average of air quality (max PM10, max CAQI and max MPI) and meteorology (mean air temperature and mean UTCI) did not improve the models. Using the mean air temperature, we found immediate effects of heat stress (RR 1.0013, 95% CI: 0.9983-1.0043) and by 3 days delayed effects of cold stress (RR: 1.0184, 95% CI: 1.0117-1.0252). The results for air quality differ between both air quality indices and PM10. CAQI and MPI show a delayed impact on morbidity with a maximum RR after 2 days (MPI 1.0058, 95% CI: 1.0013-1.0102; CAQI 1.0068, 95% CI: 1.0030-1.0107). Latitude was identified as a significant meta-variable, whereas the number of inhabitants was not significant in the model.

From concepts, theory, and evidence of heterogeneity of treatment effects to methodological approaches: a primer.

PubMed

Willke, Richard J; Zheng, Zhiyuan; Subedi, Prasun; Althin, Rikard; Mullins, C Daniel

2012-12-13

Implicit in the growing interest in patient-centered outcomes research is a growing need for better evidence regarding how responses to a given intervention or treatment may vary across patients, referred to as heterogeneity of treatment effect (HTE). A variety of methods are available for exploring HTE, each associated with unique strengths and limitations. This paper reviews a selected set of methodological approaches to understanding HTE, focusing largely but not exclusively on their uses with randomized trial data. It is oriented for the "intermediate" outcomes researcher, who may already be familiar with some methods, but would value a systematic overview of both more and less familiar methods with attention to when and why they may be used. Drawing from the biomedical, statistical, epidemiological and econometrics literature, we describe the steps involved in choosing an HTE approach, focusing on whether the intent of the analysis is for exploratory, initial testing, or confirmatory testing purposes. We also map HTE methodological approaches to data considerations as well as the strengths and limitations of each approach. Methods reviewed include formal subgroup analysis, meta-analysis and meta-regression, various types of predictive risk modeling including classification and regression tree analysis, series of n-of-1 trials, latent growth and growth mixture models, quantile regression, and selected non-parametric methods. In addition to an overview of each HTE method, examples and references are provided for further reading.By guiding the selection of the methods and analysis, this review is meant to better enable outcomes researchers to understand and explore aspects of HTE in the context of patient-centered outcomes research.

QSAR by LFER model of cytotoxicity data of anti-HIV 5-phenyl-1-phenylamino-1H-imidazole derivatives using principal component factor analysis and genetic function approximation.

PubMed

Roy, Kunal; Leonard, J Thomas

2005-04-15

Cytotoxicity data of anti-HIV 5-phenyl-1-phenylamino-1H-imidazole derivatives were subjected to quantitative structure-activity relationship (QSAR) study using linear free energy related (LFER) model of Hansch using electronic (Hammett sigma), hydrophobicity (pi) and steric (molar refractivity and STERIMOL L, B1, B2, B3 and B4) parameters of phenyl ring substituents of the compounds, along with appropriate indicator variables. Principal component factor analysis (FA) was used as the data-preprocessing step to identify the important predictor variables contributing to the response variable and to avoid collinearities among them. The generated multiple linear regression (MLR) equations were statistically validated using leave-one-out technique. Genetic function approximation (GFA) was also used on the same data set to develop QSAR equations, which produced the same best equation as obtained with FA-MLR. The final equation is of acceptable statistical quality (explained variance 80.2%) and predictive potential (leave-one-out predicted variance 74%). The analysis explores the structural and physicochemical contributions of the compounds for cytotoxicity. A thiol substituent at 2 position of the imidazole nucleus decreases cytotoxicity when compared to the corresponding unsubstituted congener. Presence of hydrogen bond donor group at meta position of the phenyl ring present at 5 position of the imidazole nucleus also reduces cytotoxicity. Additionally, absence of any substituent at 2 and 3 positions of the phenyl ring of 1-phenylamino fragment reduces the cytotoxicity. The negative coefficient of sigmap indicates that presence of electron-withdrawing substituents at the para position of the phenyl ring of the 1-phenylamino fragment is not favourable for the cytotoxicity. Again, lipophilicity of meta substituents of the 5-phenyl ring increases cytotoxicity. The coefficients of molar refractivity (MRm) and STERIMOL parameters for meta substituents (Lm, B1m and B4m) of the phenyl ring of 1-phenylamino fragment indicate that the length, width and overall size of meta substituents are conducive factors for the cytotoxicity.

A General Model for Estimating and Correcting the Effects of Nonindependence in Meta-Analysis.

ERIC Educational Resources Information Center

Strube, Michael J.

A general model is described which can be used to represent the four common types of meta-analysis: (1) estimation of effect size by combining study outcomes; (2) estimation of effect size by contrasting study outcomes; (3) estimation of statistical significance by combining study outcomes; and (4) estimation of statistical significance by…

Ego Depletion and the Strength Model of Self-Control: A Meta-Analysis

ERIC Educational Resources Information Center

Hagger, Martin S.; Wood, Chantelle; Stiff, Chris; Chatzisarantis, Nikos L. D.

2010-01-01

According to the strength model, self-control is a finite resource that determines capacity for effortful control over dominant responses and, once expended, leads to impaired self-control task performance, known as "ego depletion". A meta-analysis of 83 studies tested the effect of ego depletion on task performance and related outcomes,…

Dealing with Feeling: A Meta-Analysis of the Effectiveness of Strategies Derived from the Process Model of Emotion Regulation

ERIC Educational Resources Information Center

Webb, Thomas L.; Miles, Eleanor; Sheeran, Paschal

2012-01-01

The present meta-analysis investigated the effectiveness of strategies derived from the process model of emotion regulation in modifying emotional outcomes as indexed by experiential, behavioral, and physiological measures. A systematic search of the literature identified 306 experimental comparisons of different emotion regulation (ER)…

The Effectiveness of Physical Models in Teaching Anatomy: A Meta-Analysis of Comparative Studies

ERIC Educational Resources Information Center

Yammine, Kaissar; Violato, Claudio

2016-01-01

There are various educational methods used in anatomy teaching. While three dimensional (3D) visualization technologies are gaining ground due to their ever-increasing realism, reports investigating physical models as a low-cost 3D traditional method are still the subject of considerable interest. The aim of this meta-analysis is to quantitatively…

Interventions for reducing fear of childbirth: A systematic review and meta-analysis of clinical trials.

PubMed

MoghaddamHosseini, Vahideh; Nazarzadeh, Milad; Jahanfar, Shayesteh

2017-11-07

Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I 2 index and was further explored in meta-regression model and subgroup analyses. Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth; however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and individual patient data meta-analysis are warranted for assessing the association. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Evidence for an anterior-posterior differentiation in the human hippocampal formation revealed by meta-analytic parcellation of fMRI coordinate maps: focus on the subiculum.

PubMed

Chase, Henry W; Clos, Mareike; Dibble, Sofia; Fox, Peter; Grace, Anthony A; Phillips, Mary L; Eickhoff, Simon B

2015-06-01

Previous studies, predominantly in experimental animals, have suggested the presence of a differentiation of function across the hippocampal formation. In rodents, ventral regions are thought to be involved in emotional behavior while dorsal regions mediate cognitive or spatial processes. Using a combination of modeling the co-occurrence of significant activations across thousands of neuroimaging experiments and subsequent data-driven clustering of these data we were able to provide evidence of distinct subregions within a region corresponding to the human subiculum, a critical hub within the hippocampal formation. This connectivity-based model consists of a bilateral anterior region, as well as separate posterior and intermediate regions on each hemisphere. Functional connectivity assessed both by meta-analytic and resting fMRI approaches revealed that more anterior regions were more strongly connected to the default mode network, and more posterior regions were more strongly connected to 'task positive' regions. In addition, our analysis revealed that the anterior subregion was functionally connected to the ventral striatum, midbrain and amygdala, a circuit that is central to models of stress and motivated behavior. Analysis of a behavioral taxonomy provided evidence for a role for each subregion in mnemonic processing, as well as implication of the anterior subregion in emotional and visual processing and the right posterior subregion in reward processing. These findings lend support to models which posit anterior-posterior differentiation of function within the human hippocampal formation and complement other early steps toward a comparative (cross-species) model of the region. Copyright © 2015 Elsevier Inc. All rights reserved.

The Prevalence of Metabolic Syndrome and Its Related Factors among Adults in Palestine: A Meta-Analysis.

PubMed

El Bilbeisi, Abdel Hamid; Shab-Bidar, Sakineh; Jackson, Diane; Djafarian, Kurosh

2017-01-01

Metabolic syndrome (MetS)is increasingly becoming a challenging public health issue in Palestine. The current burden of MetS in the country is unknown. There has been limited research on the prevalence of MetS. This meta-analysis is the first to estimate the population prevalence of MetS and its related factors among adults in Palestine. A PRISMA systematic search appraisal and meta-analysis were conducted. A systematic literature search of PubMed, Scopus and Google Scholar was conducted in December 2014 up to February 2015. Generic, methodological and statistical data was extracted from the eligible studies which reported MetS prevalence. A random effect meta-analysis was conducted on crude MetS prevalence rates. Heterogeneity was assessed by Cochran's Q and I 2 tests. Subgroup analyses were also performed according to the predefined criteria. The literature search yielded a total of 49 studies. Eight papers were included in the final analysis with sample size ranging 163 to 992. In addition, 2937 cases with MetS among people aged 15 years or more were estimated in Palestine between 2001 and 2014. There was high heterogeneity among studies (I 2 = 95.8% p<0.001). The prevalence of MetS was 37.0% among adult Palestinians population ranging from 17 to 59.5%. Subgroup analysis did not show source of heterogeneity based on subject's health status and MetS criteria. Our meta-analysis clearly demonstrates that MetS is highly prevalent (37.0%) among Palestinian adults. The high prevalence of MetS in Palestine should be seriously considered and planners should take steps to reduce it.

Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

PubMed

Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

2018-01-01

Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p < 0.05). Correlation between lipid profile and genotypes has confirmed the significant relation between triglycerides and rs646218 and rs1105364 6polymorphisms. However, rs11053646 polymorphism was correlated with HDLC (p = 0.04). Genotypes were examined in both males' vs. males and females' vs. females in cases and control and we concluded that in rs11053646 polymorphisms with male subjects compared between cases and controls found to be associated with dominant model heterozygote genotypes (p < 0.05). The results of the current study confirmed the SORT1 and OLR1  SNPs were associated in the Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

Association of inorganic arsenic exposure with liver cancer mortality: A meta-analysis.

PubMed

Wang, Weijing; Cheng, Shuo; Zhang, Dongfeng

2014-11-01

The association of long-term inorganic arsenic (iAs) exposure through drinking water with risk of liver cancer mortality remains controversial. Therefore, we reviewed and quantitatively summarized the evidence from observational studies with a meta-analysis. Pertinent studies were identified by searching PubMed and China National Knowledge Infrastructure through May 2014 and by reviewing the reference lists of retrieved articles. Studies that reported standardized mortality ratios (SMRs) with 95% confidence interval (95% CIs) for the association of iAs in drinking water with liver cancer were eligible. The random effect model was adopted as the pooling method to generate summary effect estimates (meta-SMRs). Of the 4851 articles identified through searching databases, 7 articles including 12 studies were included in the meta-analysis. The meta-SMR with 95% CI of liver cancer for the highest versus lowest category of iAs exposure level in drinking water was 1.80 (1.61 to 2.02). Furthermore, an increased risk of liver cancer mortality was found in both females [1.80 (1.45 to 2.24)] and males [1.84 (1.56 to 2.16)]. In subgroup analysis, the meta-SMRs were 1.93 (1.72 to 2.15) for cohort studies, 1.60 (1.22 to 2.10) for ecological studies, 1.93 (1.72 to 2.15) for studies conducted in Asia, and 1.60 (1.22 to 2.10) for studies conducted in South America, respectively. After removing the 3 studies conducted by Smith et al. (having two studies separately for males and females) and Chen et al. that had a strong effect on heterogeneity, a significant association was also found [1.85 (1.72 to 1.99)]. This meta-analysis indicates that long-term iAs exposure through drinking water increases the risk of liver cancer mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Overlapping meta-analyses on the same topic: survey of published studies.

PubMed

Siontis, Konstantinos C; Hernandez-Boussard, Tina; Ioannidis, John P A

2013-07-19

To assess how common it is to have multiple overlapping meta-analyses of randomized trials published on the same topic. Survey of published meta-analyses. PubMed. Meta-analyses published in 2010 were identified, and 5% of them were randomly selected. We further selected those that included randomized trials and examined effectiveness of any medical intervention. For eligible meta-analyses, we searched for other meta-analyses on the same topic (covering the same comparisons, indications/settings, and outcomes or overlapping subsets of them) published until February 2013. Of 73 eligible meta-analyses published in 2010, 49 (67%) had at least one other overlapping meta-analysis (median two meta-analyses per topic, interquartile range 1-4, maximum 13). In 17 topics at least one author was involved in at least two of the overlapping meta-analyses. No characteristics of the index meta-analyses were associated with the potential for overlapping meta-analyses. Among pairs of overlapping meta-analyses in 20 randomly selected topics, 13 of the more recent meta-analyses did not include any additional outcomes. In three of the four topics with eight or more published meta-analyses, many meta-analyses examined only a subset of the eligible interventions or indications/settings covered by the index meta-analysis. Conversely, for statins in the prevention of atrial fibrillation after cardiac surgery, 11 meta-analyses were published with similar eligibility criteria for interventions and setting: there was still variability on which studies were included, but the results were always similar or even identical across meta-analyses. While some independent replication of meta-analyses by different teams is possibly useful, the overall picture suggests that there is a waste of efforts with many topics covered by multiple overlapping meta-analyses.

Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies.

PubMed

Zwetsloot, P P; Kouwenberg, L H J A; Sena, E S; Eding, J E; den Ruijter, H M; Sluijter, J P G; Pasterkamp, G; Doevendans, P A; Hoefer, I E; Chamuleau, S A J; van Hout, G P J; Jansen Of Lorkeers, S J

2017-10-27

Large animal models are essential for the development of novel therapeutics for myocardial infarction. To optimize translation, we need to assess the effect of experimental design on disease outcome and model experimental design to resemble the clinical course of MI. The aim of this study is therefore to systematically investigate how experimental decisions affect outcome measurements in large animal MI models. We used control animal-data from two independent meta-analyses of large animal MI models. All variables of interest were pre-defined. We performed univariable and multivariable meta-regression to analyze whether these variables influenced infarct size and ejection fraction. Our analyses incorporated 246 relevant studies. Multivariable meta-regression revealed that infarct size and cardiac function were influenced independently by choice of species, sex, co-medication, occlusion type, occluded vessel, quantification method, ischemia duration and follow-up duration. We provide strong systematic evidence that commonly used endpoints significantly depend on study design and biological variation. This makes direct comparison of different study-results difficult and calls for standardized models. Researchers should take this into account when designing large animal studies to most closely mimic the clinical course of MI and enable translational success.

Association of the F13A1 Val34Leu polymorphism and recurrent pregnancy loss: A meta-analysis.

PubMed

Jung, Jae Hyun; Kim, Jae-Hoon; Song, Gwan Gyu; Choi, Sung Jae

2017-08-01

Factor XIII (FXIII) plays role in stabilizing the linkage between fibrins during blood clotting and has been implicated in recurrent pregnancy loss (RPL). The relationship between the Val34Leu polymorphism in F13A1, which encodes the enzymatic subunit of FXIII, and RPL is unclear. The aim of this meta-analysis was to evaluate the association betweenF13A1 Val34Leu and the risk of RPL. We performed a meta-analysis of 11 studies involving 1092 cases and 678 controls using published literature from PubMed and Embase. We detected an association in recessive (Val/Val vs. Val/Leu+Leu/Leu; OR=0.71, 95% CI=0.51-0.99, P=0.04), and one of the two co-dominant (Val/Val vs. Val/Leu; OR=0.71, 95% CI=0.52-0.98, P=0.03) models of in heritance. Subgroup analysis revealed that the F13A1 Val34Leu polymorphism was associated with RPL in Asians (Val vs. Leu; OR=0.53, CI=0.33-0.85, P=0.01). However, there was no association between F13A1 Val34Leu and RPL in Europeans and South Americans. Our meta-analysis supports an association between F13A1 Val34Leu and RPL. Copyright © 2017 Elsevier B.V. All rights reserved.

The association between dietary zinc intake and risk of pancreatic cancer: a meta-analysis.

PubMed

Li, Li; Gai, Xuesong

2017-06-30

Previous reports have suggested a potential association on dietary zinc intake with the risk of pancreatic cancer. Since the associations between different studies were controversial, we therefore conducted a meta-analysis to reassess the relationship between dietary zinc intake and pancreatic cancer risk. A comprehensive search from the databases of PubMed, Embase, Web of Science, and Medline was performed until January 31, 2017. Relative risk (RR) with 95% confidence intervals (CI) derived by using random effect model was used. Sensitivity analysis and publication bias were conducted. Our meta-analysis was based on seven studies involving 1659 cases, including two prospective cohort studies and five case-control studies. The total RR of pancreatic cancer risk for the highest versus the lowest categories of dietary zinc intake was 0.798 (0.621-0.984), with its significant heterogeneity among studies ( I 2 =58.2%, P =0.026). The average Newcastle-Ottawa scale (NOS) score was 7.29, suggesting a high quality. There was no publication bias in the meta-analysis about dietary zinc intake on the risk of pancreatic cancer. Subgroup analyses showed that dietary zinc intake could reduce the risk of pancreatic cancer in case-control studies and among American populations. In conclusion, we found that highest category of dietary zinc intake can significantly reduce the risk of pancreatic cancer, especially among American populations. © 2017 The Author(s).

Skeletal adaptations associated with pre-pubertal gymnastics participation as determined by DXA and pQCT: a systematic review and meta-analysis.

PubMed

Burt, Lauren A; Greene, David A; Ducher, Gaele; Naughton, Geraldine A

2013-05-01

Participation in gymnastics prior to puberty offers an intriguing and unique model, particularly in girls. The individuality comes from both upper and lower limbs being exposed to high mechanical loading through year long intensive training programs, initiated at a young age. Studying this unique model and the associated changes in musculoskeletal health during growth is an area of specific interest. Previous reviews on gymnastics participation and bone health have been broad; and not limited to a particular maturation period, such as pre-puberty. To determine the difference in skeletal health between pre-pubertal girls participating in gymnastics compared with non-gymnasts. Meta-analysis. Following a systematic search, 17 studies were included in this meta-analysis. All studies used dual-energy X-ray absorptiometry to assess bone mineral density and bone mineral content. In addition, two studies included peripheral quantitative computed tomography. Following the implementation of a random effects model, gymnasts were found to have greater bone properties than non-gymnasts. The largest difference in bone health between gymnasts and non-gymnasts was observed in peripheral quantitative computed tomography-derived volumetric bone mineral density at the distal radius (d=1.06). Participation in gymnastics during pre-pubertal growth was associated with skeletal health benefits, particularly to the upper body. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Eliciting mixed emotions: a meta-analysis comparing models, types, and measures

PubMed Central

Berrios, Raul; Totterdell, Peter; Kellett, Stephen

2015-01-01

The idea that people can experience two oppositely valenced emotions has been controversial ever since early attempts to investigate the construct of mixed emotions. This meta-analysis examined the robustness with which mixed emotions have been elicited experimentally. A systematic literature search identified 63 experimental studies that instigated the experience of mixed emotions. Studies were distinguished according to the structure of the underlying affect model—dimensional or discrete—as well as according to the type of mixed emotions studied (e.g., happy-sad, fearful-happy, positive-negative). The meta-analysis using a random-effects model revealed a moderate to high effect size for the elicitation of mixed emotions (dIG+ = 0.77), which remained consistent regardless of the structure of the affect model, and across different types of mixed emotions. Several methodological and design moderators were tested. Studies using the minimum index (i.e., the minimum value between a pair of opposite valenced affects) resulted in smaller effect sizes, whereas subjective measures of mixed emotions increased the effect sizes. The presence of more women in the samples was also associated with larger effect sizes. The current study indicates that mixed emotions are a robust, measurable and non-artifactual experience. The results are discussed in terms of the implications for an affect system that has greater versatility and flexibility than previously thought. PMID:25926805

Breast and Bottle Feeding as Risk Factors for Dental Caries: A Systematic Review and Meta-Analysis

PubMed Central

Avila, Walesca M.; Pordeus, Isabela A.; Paiva, Saul M.; Martins, Carolina C.

2015-01-01

Understanding the role that breastfeeding and bottle feeding play in the development of dental caries during childhood is essential in helping dentists and parents and care providers prevent the disease, and also for the development of effective public health policies. However, the issue is not yet fully understood. The aim of this systematic review and meta-analysis was to search for scientific evidence in response to the question: Do bottle fed children have more dental caries in primary dentition than breastfed children? Seven electronic databases and grey literature were used in the search. The protocol number of the study is PROSPERO CRD 42014006534. Two independent reviewers selected the studies, extracted data and evaluated risk of bias by quality assessment. A random effect model was used for meta-analysis, and the summary effect measure were calculated by odds ratio (OR) and 95% CI. Seven studies were included: five cross-sectional, one case-control and one cohort study. A meta-analysis of cross-sectional studies showed that breastfed children were less affected by dental caries than bottle fed children (OR: 0.43; 95%CI: 0.23–0.80). Four studies showed that bottle fed children had more dental caries (p<0.05), while three studies found no such association (p>0.05). The scientific evidence therefore indicated that breastfeeding can protect against dental caries in early childhood. The benefits of breastfeeding until age two is recommended by WHO/UNICEF guidelines. Further prospective observational cohort studies are needed to strengthen the evidence. PMID:26579710

Updated systematic review and meta-analysis of the performance of risk prediction rules in children and young people with febrile neutropenia.

PubMed

Phillips, Robert S; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia.

Updated Systematic Review and Meta-Analysis of the Performance of Risk Prediction Rules in Children and Young People with Febrile Neutropenia

PubMed Central

Phillips, Robert S.; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Introduction Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. Results We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. Conclusion The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia. PMID:22693615

Prevalence of Gestational Diabetes Mellitus in Eastern and Southeastern Asia: A Systematic Review and Meta-Analysis

PubMed Central

Binns, Colin W.; Duong, Dat Van; Lee, Andy H.

2018-01-01

Aim To review the prevalence of gestational diabetes mellitus (GDM) in Eastern and Southeastern Asia. Methods We systematically searched for observational studies on GDM prevalence from January 2000 to December 2016. Inclusion criteria were original English papers, with full texts published in peer-reviewed journals. The quality of included studies was evaluated using the guidelines of the National Health and Medical Research Council, Australia. Fixed effects and random effects models were used to estimate the summary prevalence of GDM and the corresponding 95% confidence intervals (CI). Results A total of 4415 papers were screened, and 48 studies with 63 GDM prevalence observations were included in the final review. The pooled prevalence of GDM was 10.1% (95% CI: 6.5%–15.7%), despite substantial variations across nations. The prevalence of GDM in lower- or upper-middle income countries was about 64% higher than in their high-income counterparts. Moreover, the one-step screening method was twice more likely to be used in diagnosing GDM when compared to the two-step screening procedure. Conclusions The prevalence of GDM in Eastern and Southeastern Asia was high and varied among and within countries. There is a need for international uniformity in screening strategies and diagnostic criteria for GDM. PMID:29675432

A Practical Guide to Conducting a Systematic Review and Meta-analysis of Health State Utility Values.

PubMed

Petrou, Stavros; Kwon, Joseph; Madan, Jason

2018-05-10

Economic analysts are increasingly likely to rely on systematic reviews and meta-analyses of health state utility values to inform the parameter inputs of decision-analytic modelling-based economic evaluations. Beyond the context of economic evaluation, evidence from systematic reviews and meta-analyses of health state utility values can be used to inform broader health policy decisions. This paper provides practical guidance on how to conduct a systematic review and meta-analysis of health state utility values. The paper outlines a number of stages in conducting a systematic review, including identifying the appropriate evidence, study selection, data extraction and presentation, and quality and relevance assessment. The paper outlines three broad approaches that can be used to synthesise multiple estimates of health utilities for a given health state or condition, namely fixed-effect meta-analysis, random-effects meta-analysis and mixed-effects meta-regression. Each approach is illustrated by a synthesis of utility values for a hypothetical decision problem, and software code is provided. The paper highlights a number of methodological issues pertinent to the conduct of meta-analysis or meta-regression. These include the importance of limiting synthesis to 'comparable' utility estimates, for example those derived using common utility measurement approaches and sources of valuation; the effects of reliance on limited or poorly reported published data from primary utility assessment studies; the use of aggregate outcomes within analyses; approaches to generating measures of uncertainty; handling of median utility values; challenges surrounding the disentanglement of utility estimates collected serially within the context of prospective observational studies or prospective randomised trials; challenges surrounding the disentanglement of intervention effects; and approaches to measuring model validity. Areas of methodological debate and avenues for future research are highlighted.

Meta-analyzing dependent correlations: an SPSS macro and an R script.

PubMed

Cheung, Shu Fai; Chan, Darius K-S

2014-06-01

The presence of dependent correlation is a common problem in meta-analysis. Cheung and Chan (2004, 2008) have shown that samplewise-adjusted procedures perform better than the more commonly adopted simple within-sample mean procedures. However, samplewise-adjusted procedures have rarely been applied in meta-analytic reviews, probably due to the lack of suitable ready-to-use programs. In this article, we compare the samplewise-adjusted procedures with existing procedures to handle dependent effect sizes, and present the samplewise-adjusted procedures in a way that will make them more accessible to researchers conducting meta-analysis. We also introduce two tools, an SPSS macro and an R script, that researchers can apply to their meta-analyses; these tools are compatible with existing meta-analysis software packages.

Crustacean communities in coastal ephemeral pools in the Araucanía region (38° S, Chile).

PubMed

De Los Ríos-Escalante, P; Acevedo, P

2016-01-01

The fauna communities of ephemeral pools in southern Chile are characterized by heterogeneity of crustacean taxa; nevertheless, no detailed studies exist of their community structure. The aim of the present study was to analyze the crustacean community structure in two groups of ephemeral pools (Puaucho and Nigue pools) in the coastal zone of the Araucanía region. A correlation matrix was made by species abundance against temperature, conductivity, pH and total dissolved solids. In a second step, a null model for species co-occurrence was applied to the total data and to each group. The results for total data revealed a significant direct relation between the abundance of H. costera, C. dubia and Mesocyclops. For the Puaucho pools, the same results were found together with direct associations with total dissolved solids, conductivity and pH. Finally, different results were found for the Nigue pools, with no clear significant associations, either direct or indirect, between the abundance of different crustacean taxa and abiotic parameters. These results were supported by the co-occurrence null model analysis, which revealed the presence of regulator factors for the total data, and for each of the two groups. Ecological topics are discussed with emphasis on meta-community dynamics.

Effect of High-Frequency Transcranial Magnetic Stimulation on Craving in Substance Use Disorder: A Meta-Analysis.

PubMed

Maiti, Rituparna; Mishra, Biswa Ranjan; Hota, Debasish

2017-01-01

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive, neuromodulatory tool, has been used to reduce craving in different substance use disorders. There are some studies that have reported conflicting and inconclusive results; therefore, this meta-analysis was conducted to evaluate the effect of high-frequency rTMS on craving in substance use disorder and to investigate the reasons behind the inconsistency across the studies. The authors searched clinical trials from MEDLINE, Cochrane databases, and International Clinical Trials Registry Platform. The PRISMA guidelines, as well as recommended meta-analysis practices, were followed in the selection process, analysis, and reporting of the findings. The effect estimate used was the standardized mean difference (Hedge's g), and heterogeneity across the considered studies was explored using subgroup analyses. The quality assessment was done using the Cochrane risk of bias tool, and sensitivity analysis was performed to check the influences on effect size by statistical models. After screening and assessment of eligibility, finally 10 studies were included for meta-analysis, which includes six studies on alcohol and four studies on nicotine use disorder. The random-model analysis revealed a pooled effect size of 0.75 (95% CI=0.29 to 1.21, p=0.001), whereas the fixed-model analysis showed a large effect size of 0.87 (95% CI=0.63 to 1.12, p<0.00001). Subgroup analysis for alcohol use disorder showed an effect size of -0.06 (95% CI=-0.89 to 0.77, p=0.88). In the case of nicotine use disorder, random-model analysis revealed an effect size of 1.00 (95% CI=0.48 to 1.55, p=0.0001), whereas fixed-model analysis also showed a large effect size of 0.96 (95% CI=0.71 to 1.22). The present meta-analysis identified a beneficial effect of high-frequency rTMS on craving associated with nicotine use disorder but not alcohol use disorder.

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

PubMed Central

Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; Heijer, Martin den; Dieplinger, Benjamin; Ding, Jingzhong; Dörr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O’Connell, Jeff; O’Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Boerwinkle, Eric; Campbell, Harry; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Münzel, Thomas; Newman, Anne; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Völker, Uwe; Wright, Alan F.; Wichmann, H.-Erich; Wilson, James F.; Witteman, Jacqueline C.M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian

2012-01-01

Background Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results Continuous ABI and PAD (ABI≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β= −0.006, p=2.46x10−8). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10−9). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI : DAB21P (rs13290547, p=3.6x10−5); CYBA (rs3794624, p=6.3x10−5); and rs1122608 (LDLR, p=0.0026). Conclusions GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI. PMID:22199011

Comparison of repaglinide and metformin versus metformin alone for type 2 diabetes: a meta-analysis of randomized controlled trials.

PubMed

Yin, Jinjin; Deng, Houliang; Qin, Shumin; Tang, Waijiao; Zeng, Lu; Zhou, Benjie

2014-09-01

We conducted a meta-analysis to compare the efficacy and safety of repaglinide plus metformin with metformin alone on type 2 diabetes. Twenty-two studies were included in this meta-analysis. Results showed combination therapy was safe and could gain better outcomes in glycemic control. Well-designed studies are required to confirm this conclusion. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.

PubMed

Barron, Daniel S; Fox, Peter T; Pardoe, Heath; Lancaster, Jack; Price, Larry R; Blackmon, Karen; Berry, Kristen; Cavazos, Jose E; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas

2015-01-01

Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

Advances in the meta-analysis of heterogeneous clinical trials II: The quality effects model.

PubMed

Doi, Suhail A R; Barendregt, Jan J; Khan, Shahjahan; Thalib, Lukman; Williams, Gail M

2015-11-01

This article examines the performance of the updated quality effects (QE) estimator for meta-analysis of heterogeneous studies. It is shown that this approach leads to a decreased mean squared error (MSE) of the estimator while maintaining the nominal level of coverage probability of the confidence interval. Extensive simulation studies confirm that this approach leads to the maintenance of the correct coverage probability of the confidence interval, regardless of the level of heterogeneity, as well as a lower observed variance compared to the random effects (RE) model. The QE model is robust to subjectivity in quality assessment down to completely random entry, in which case its MSE equals that of the RE estimator. When the proposed QE method is applied to a meta-analysis of magnesium for myocardial infarction data, the pooled mortality odds ratio (OR) becomes 0.81 (95% CI 0.61-1.08) which favors the larger studies but also reflects the increased uncertainty around the pooled estimate. In comparison, under the RE model, the pooled mortality OR is 0.71 (95% CI 0.57-0.89) which is less conservative than that of the QE results. The new estimation method has been implemented into the free meta-analysis software MetaXL which allows comparison of alternative estimators and can be downloaded from www.epigear.com. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis

PubMed Central

Schramm, Elisabeth; Weitz, Erica S; Salanti, Georgia; Efthimiou, Orestis; Michalak, Johannes; Watanabe, Norio; Keller, Martin B; Kocsis, James H; Klein, Daniel N; Cuijpers, Pim

2016-01-01

Introduction Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. Methods and analysis We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. Ethics and dissemination This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. Trial registration number CRD42016035886. PMID:27147393

Exposure to fluoride in drinking water and hip fracture risk: a meta-analysis of observational studies.

PubMed

Yin, Xin-Hai; Huang, Guang-Lei; Lin, Du-Ren; Wan, Cheng-Cheng; Wang, Ya-Dong; Song, Ju-Kun; Xu, Ping

2015-01-01

Many observational studies have shown that exposure to fluoride in drinking water is associated with hip fracture risk. However, the findings are varied or even contradictory. In this work, we performed a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk. PubMed and EMBASE databases were searched to identify relevant observational studies from the time of inception until March 2014 without restrictions. Data from the included studies were extracted and analyzed by two authors. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random- or fixed-effects models as appropriate. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Finally, publication bias was assessed. Fourteen observational studies involving thirteen cohort studies and one case-control study were included in the meta-analysis. Exposure to fluoride in drinking water does not significantly increase the incidence of hip fracture (RRs, 1.05; 95% CIs, 0.96-1.15). Sensitivity analyses based on adjustment for covariates, effect measure, country, sex, sample size, quality of Newcastle-Ottawa Scale scores, and follow-up period validated the strength of the results. Meta-regression showed that country, gender, quality of Newcastle-Ottawa Scale scores, adjustment for covariates and sample size were not sources of heterogeneity. Little evidence of publication bias was observed. The present meta-analysis suggests that chronic fluoride exposure from drinking water does not significantly increase the risk of hip fracture. Given the potential confounding factors and exposure misclassification, further large-scale, high-quality studies are needed to evaluate the association between exposure to fluoride in drinking water and hip fracture risk.

Exposure to Fluoride in Drinking Water and Hip Fracture Risk: A Meta-Analysis of Observational Studies

PubMed Central

Yin, Xin-Hai; Huang, Guang-Lei; Lin, Du-Ren; Wan, Cheng-Cheng; Wang, Ya-Dong; Song, Ju-Kun; Xu, Ping

2015-01-01

Background Many observational studies have shown that exposure to fluoride in drinking water is associated with hip fracture risk. However, the findings are varied or even contradictory. In this work, we performed a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk. Methods PubMed and EMBASE databases were searched to identify relevant observational studies from the time of inception until March 2014 without restrictions. Data from the included studies were extracted and analyzed by two authors. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random- or fixed-effects models as appropriate. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Finally, publication bias was assessed. Results Fourteen observational studies involving thirteen cohort studies and one case-control study were included in the meta-analysis. Exposure to fluoride in drinking water does not significantly increase the incidence of hip fracture (RRs, 1.05; 95% CIs, 0.96–1.15). Sensitivity analyses based on adjustment for covariates, effect measure, country, sex, sample size, quality of Newcastle–Ottawa Scale scores, and follow-up period validated the strength of the results. Meta-regression showed that country, gender, quality of Newcastle–Ottawa Scale scores, adjustment for covariates and sample size were not sources of heterogeneity. Little evidence of publication bias was observed. Conclusion The present meta-analysis suggests that chronic fluoride exposure from drinking water does not significantly increase the risk of hip fracture. Given the potential confounding factors and exposure misclassification, further large-scale, high-quality studies are needed to evaluate the association between exposure to fluoride in drinking water and hip fracture risk. PMID:26020536

Estimating the Global Incidence of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review for Central Nervous System Vascular Lesions and Meta-Analysis of Ruptured Aneurysms.

PubMed

Hughes, Joshua D; Bond, Kamila M; Mekary, Rania A; Dewan, Michael C; Rattani, Abbas; Baticulon, Ronnie; Kato, Yoko; Azevedo-Filho, Hildo; Morcos, Jacques J; Park, Kee B

2018-04-09

There is increasing acknowledgement that surgical care is important in global health initiatives. In particular, neurosurgical care is as limited as 1 per 10 million people in parts of the world. We performed a systematic literature review to examine the worldwide incidence of central nervous system vascular lesions and a meta-analysis of aneurysmal subarachnoid hemorrhage (aSAH) to define the disease burden and inform neurosurgical global health efforts. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to estimate the global epidemiology of central nervous system vascular lesions, including unruptured and ruptured aneurysms, arteriovenous malformations, cavernous malformations, dural arteriovenous fistulas, developmental venous anomalies, and vein of Galen malformations. Results were organized by World Health Organization regions. After literature review, because of a lack of data from particular World Health Organization regions, we determined we could only provide an estimate of aSAH. Using data from studies with aSAH and 12 high-quality stroke studies from regions lacking data, we meta-analyzed the yearly crude incidence of aSAH per 100,000 persons. Estimates were generated via random-effects models. From an initial yield of 1492 studies, 46 manuscripts on aSAH incidence were included. The final meta-analysis included 58 studies from 31 different countries. We estimated the global crude incidence for aSAH to be 6.67 per 100,000 persons with a wide variation across WHO regions from 0.71 to 12.38 per 100,000 persons. Worldwide, almost 500,000 individuals will suffer from aSAH each year, with almost two-thirds in low- and middle-income countries. Copyright © 2018 Elsevier Inc. All rights reserved.

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data

PubMed Central

Bax, Leon; Yu, Ly-Mee; Ikeda, Noriaki; Tsuruta, Harukazu; Moons, Karel GM

2006-01-01

Background Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis. Results We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features. Conclusion The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via or . PMID:17038197

The association between obesity and dengue severity among pediatric patients: A systematic review and meta-analysis

PubMed Central

Dahlui, Maznah; Jamil, Nor’ashikin; Peramalah, Devi; Wai, Hoe Victor Chee; Bulgiba, Awang; Rampal, Sanjay

2018-01-01

Background Severe dengue infection often has unpredictable clinical progressions and outcomes. Obesity may play a role in the deterioration of dengue infection due to stronger body immune responses. Several studies found that obese dengue patients have a more severe presentation with a poorer prognosis. However, the association was inconclusive due to the variation in the results of earlier studies. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between obesity and dengue severity. Methods We performed a systematic search of relevant studies on Ovid (MEDLINE), EMBASE, the Cochrane Library, Web of Science, Scopus and grey literature databases. At least two authors independently conducted the literature search, selecting eligible studies, and extracting data. Meta-analysis using random-effects model was conducted to compute the pooled odds ratio with 95% confidence intervals (CI). Findings We obtained a total of 13,333 articles from the searches. For the final analysis, we included a total of fifteen studies among pediatric patients. Three cohort studies, two case-control studies, and one cross-sectional study found an association between obesity and dengue severity. In contrast, six cohort studies and three case-control studies found no significant relationship between obesity and dengue severity. Our meta-analysis revealed that there was 38 percent higher odds (Odds Ratio = 1.38; 95% CI:1.10, 1.73) of developing severe dengue infection among obese children compared to non-obese children. We found no heterogeneity found between studies. The differences in obesity classification, study quality, and study design do not modify the association between obesity and dengue severity. Conclusion This review found that obesity is a risk factor for dengue severity among children. The result highlights and improves our understanding that obesity might influence the severity of dengue infection. PMID:29415036

The benefit of silicone stents in primary endonasal dacryocystorhinostomy: a systematic review and meta-analysis.

PubMed

Sarode, D; Bari, D A; Cain, A C; Syed, M I; Williams, A T

2017-04-01

To critically evaluate the evidence comparing success rates of endonasal dacryocystorhinostomy (EN-DCR) with and without silicone tubing and to thus determine whether silicone intubation is beneficial in primary EN-DCR. Systematic review and meta-analysis. A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders groups trials register using a combination of various MeSH. The date of last search was January 2016. This review was limited to randomised controlled trials (RCTs) in English language. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool. Chi-square and I 2 statistics were calculated to determine the presence and extent of statistical heterogeneity. Study selection, data extraction and risk of bias scoring were performed independently by two authors in concordance with the PRISMA statement. Five RCTs (447 primary EN-DCR procedures in 426 patients) were included for analysis. Moderate interstudy statistical heterogeneity was demonstrated (Chi 2 = 6.18; d.f. = 4; I 2 = 35%). Bicanalicular silicone stents were used in 229 and not used in 218 procedures. The overall success rate of EN-DCR was 92.8% (415/447). The success rate of EN-DCR was 93.4% (214/229) with silicone tubing and 92.2% (201/218) without silicone tubing. Meta-analysis using a random-effects model showed no statistically significant difference in outcomes between the two groups (P = 0.63; RR = 0.79; 95% CI = 0.3-2.06). Our review and meta-analysis did not demonstrate an additional advantage of silicone stenting. A high-quality well-powered prospective multicentre RCT is needed to further clarify on the benefit of silicone stents. © 2016 John Wiley & Sons Ltd.

Protocol - realist and meta-narrative evidence synthesis: Evolving Standards (RAMESES)

PubMed Central

2011-01-01

Background There is growing interest in theory-driven, qualitative and mixed-method approaches to systematic review as an alternative to (or to extend and supplement) conventional Cochrane-style reviews. These approaches offer the potential to expand the knowledge base in policy-relevant areas - for example by explaining the success, failure or mixed fortunes of complex interventions. However, the quality of such reviews can be difficult to assess. This study aims to produce methodological guidance, publication standards and training resources for those seeking to use the realist and/or meta-narrative approach to systematic review. Methods/design We will: [a] collate and summarise existing literature on the principles of good practice in realist and meta-narrative systematic review; [b] consider the extent to which these principles have been followed by published and in-progress reviews, thereby identifying how rigour may be lost and how existing methods could be improved; [c] using an online Delphi method with an interdisciplinary panel of experts from academia and policy, produce a draft set of methodological steps and publication standards; [d] produce training materials with learning outcomes linked to these steps; [e] pilot these standards and training materials prospectively on real reviews-in-progress, capturing methodological and other challenges as they arise; [f] synthesise expert input, evidence review and real-time problem analysis into more definitive guidance and standards; [g] disseminate outputs to audiences in academia and policy. The outputs of the study will be threefold: 1. Quality standards and methodological guidance for realist and meta-narrative reviews for use by researchers, research sponsors, students and supervisors 2. A 'RAMESES' (Realist and Meta-review Evidence Synthesis: Evolving Standards) statement (comparable to CONSORT or PRISMA) of publication standards for such reviews, published in an open-access academic journal. 3. A training module for researchers, including learning outcomes, outline course materials and assessment criteria. Discussion Realist and meta-narrative review are relatively new approaches to systematic review whose overall place in the secondary research toolkit is not yet fully established. As with all secondary research methods, guidance on quality assurance and uniform reporting is an important step towards improving quality and consistency of studies. PMID:21843376

A Meta-Analysis of Children's Object-to-Mouth Frequency Data for Estimating Non-Dietary Ingestion Exposure

EPA Science Inventory

To improve estimates of non-dietary ingestion in probabilistic exposure modeling, a meta-analysis of children's object-to-mouth frequency was conducted using data from seven available studies representing 438 participants and ~ 1500 h of behavior observation. The analysis repres...

A Meta-Analysis of Dunn and Dunn Model Correlational Research with Adult Populations

ERIC Educational Resources Information Center

Mangino, Christine

2004-01-01

The purpose of this investigation was to conduct a quantitative synthesis of correlational research that focused on the Dunn and Dunn Learning-Style Model and was concerned with adult populations. A total of 8,661 participants from the 47 original investigations provided 386 individual effect sizes for this meta-analysis. The mean effect size was…

Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

PubMed Central

Jackson, Dan; White, Ian R; Riley, Richard D

2012-01-01

Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I2, which we call . We also provide a multivariate H2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22763950

Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis.

PubMed

Tariq, Raseen; Mukhija, Dhruvika; Gupta, Arjun; Singh, Siddharth; Pardi, Darrell S; Khanna, Sahil

2018-01-01

Statins have pleiotropic effects beyond cholesterol lowering by immune modulation. The association of statins with primary Clostridium difficile infection (CDI) is unclear as studies have reported conflicting findings. We performed a systematic review and meta-analysis to evaluate the association between statin use and CDI. We searched MEDLINE, Embase, and Web of Science from January 1978 to December 2016 for studies assessing the association between statin use and CDI. The Newcastle-Ottawa Scale was used to assess the methodologic quality of included studies. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Eight studies (6 case-control and 2 cohort) were included in the meta-analysis, which comprised 156,722 patients exposed to statins and 356,185 controls, with 34,849 total cases of CDI available in 7 studies. The rate of CDI in patients with statin use was 4.3%, compared with 7.8% in patients without statin use. An overall meta-analysis of 8 studies using the random-effects model demonstrated that statins may be associated with a decreased risk of CDI (maximally adjusted odds ratio [OR], 0.80; 95% CI, 0.66-0.97; P =0.02). There was significant heterogeneity among the studies, with an I 2 of 79%. No publication bias was seen. Meta-analysis of studies that adjusted for confounders revealed no protective effect of statins (adjusted OR, 0.84; 95% CI, 0.70-1.01; P =0.06, I 2 =75%). However, a meta-analysis of only full-text studies using the random-effects model demonstrated a decreased risk of CDI with the use of statins (OR 0.77; 95% CI, 0.61-0.99; P =0.04, I 2 =85%). Meta-analyses of existing studies suggest that patients prescribed a statin may be at decreased risk for CDI. The results must be interpreted with caution given the significant heterogeneity and lack of benefit on analysis of studies that adjusted for confounders.

Multivariate meta-analysis using individual participant data.

PubMed

Riley, R D; Price, M J; Jackson, D; Wardle, M; Gueyffier, F; Wang, J; Staessen, J A; White, I R

2015-06-01

When combining results across related studies, a multivariate meta-analysis allows the joint synthesis of correlated effect estimates from multiple outcomes. Joint synthesis can improve efficiency over separate univariate syntheses, may reduce selective outcome reporting biases, and enables joint inferences across the outcomes. A common issue is that within-study correlations needed to fit the multivariate model are unknown from published reports. However, provision of individual participant data (IPD) allows them to be calculated directly. Here, we illustrate how to use IPD to estimate within-study correlations, using a joint linear regression for multiple continuous outcomes and bootstrapping methods for binary, survival and mixed outcomes. In a meta-analysis of 10 hypertension trials, we then show how these methods enable multivariate meta-analysis to address novel clinical questions about continuous, survival and binary outcomes; treatment-covariate interactions; adjusted risk/prognostic factor effects; longitudinal data; prognostic and multiparameter models; and multiple treatment comparisons. Both frequentist and Bayesian approaches are applied, with example software code provided to derive within-study correlations and to fit the models. © 2014 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd.

Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis.

PubMed

Lewis, G N; Rice, D A; McNair, P J; Kluger, M

2015-04-01

Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A comparison of bivariate, multivariate random-effects, and Poisson correlated gamma-frailty models to meta-analyze individual patient data of ordinal scale diagnostic tests.

PubMed

Simoneau, Gabrielle; Levis, Brooke; Cuijpers, Pim; Ioannidis, John P A; Patten, Scott B; Shrier, Ian; Bombardier, Charles H; de Lima Osório, Flavia; Fann, Jesse R; Gjerdingen, Dwenda; Lamers, Femke; Lotrakul, Manote; Löwe, Bernd; Shaaban, Juwita; Stafford, Lesley; van Weert, Henk C P M; Whooley, Mary A; Wittkampf, Karin A; Yeung, Albert S; Thombs, Brett D; Benedetti, Andrea

2017-11-01

Individual patient data (IPD) meta-analyses are increasingly common in the literature. In the context of estimating the diagnostic accuracy of ordinal or semi-continuous scale tests, sensitivity and specificity are often reported for a given threshold or a small set of thresholds, and a meta-analysis is conducted via a bivariate approach to account for their correlation. When IPD are available, sensitivity and specificity can be pooled for every possible threshold. Our objective was to compare the bivariate approach, which can be applied separately at every threshold, to two multivariate methods: the ordinal multivariate random-effects model and the Poisson correlated gamma-frailty model. Our comparison was empirical, using IPD from 13 studies that evaluated the diagnostic accuracy of the 9-item Patient Health Questionnaire depression screening tool, and included simulations. The empirical comparison showed that the implementation of the two multivariate methods is more laborious in terms of computational time and sensitivity to user-supplied values compared to the bivariate approach. Simulations showed that ignoring the within-study correlation of sensitivity and specificity across thresholds did not worsen inferences with the bivariate approach compared to the Poisson model. The ordinal approach was not suitable for simulations because the model was highly sensitive to user-supplied starting values. We tentatively recommend the bivariate approach rather than more complex multivariate methods for IPD diagnostic accuracy meta-analyses of ordinal scale tests, although the limited type of diagnostic data considered in the simulation study restricts the generalization of our findings. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Excimer Laser Versus Phakic Intraocular Lenses for Myopia and Astigmatism: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Chen, Haiting; Liu, Yu; Niu, Guangzeng; Ma, Jingxue

2018-05-01

Meta-analysis of randomized controlled trials (RCTs) which compared excimer laser refractive surgery and phakic intraocular lenses (PIOLs) for the treatment of myopia and astigmatism. An electronic literature search was performed using the PubMed, EBSCO, CNKI, and Cochrane Library database to identify prospective RCTs which compared excimer laser refractive surgery and PIOL with a follow-up time of at least 12 months. Efficacy, accuracy, safety outcomes, and complications were analyzed by standardized mean difference, risk ratio, and the pooled estimates according to a fixed effect model or random effect model. This review included 5 RCTs with a sum of 405 eyes. The range of myopia was 6.0 to 20.0 D with up to 4.0 D of astigmatism. The PIOL group was more likely to achieve a spherical equivalence within±1.0 D of target refraction at 12 months postoperatively (P=0.009), and was less likely to lose one or more lines of best spectacle corrected visual acuity than the LASER group (P=0.002). On the whole, there is no significant difference in efficacy and complications between the two kinds of surgeries. This meta-analysis indicated that PIOLs were safer and more accurate within 12 months of follow-up compared with excimer laser surgical for refractive errors.

Evidence synthesis for medical decision making and the appropriate use of quality scores.

PubMed

Doi, Suhail A R

2014-09-01

Meta-analyses today continue to be run using conventional random-effects models that ignore tangible information from studies such as the quality of the studies involved, despite the expectation that results of better quality studies reflect more valid results. Previous research has suggested that quality scores derived from such quality appraisals are unlikely to be useful in meta-analysis, because they would produce biased estimates of effects that are unlikely to be offset by a variance reduction within the studied models. However, previous discussions took place in the context of such scores viewed in terms of their ability to maximize their association with both the magnitude and direction of bias. In this review, another look is taken at this concept, this time asserting that probabilistic bias quantification is not possible or even required of quality scores when used in meta-analysis for redistribution of weights. The use of such a model is contrasted with the conventional random effects model of meta-analysis to demonstrate why the latter is inadequate in the face of a properly specified quality score weighting method. © 2014 Marshfield Clinic.

Multivariate meta-analysis with an increasing number of parameters

PubMed Central

Boca, Simina M.; Pfeiffer, Ruth M.; Sampson, Joshua N.

2017-01-01

Summary Meta-analysis can average estimates of multiple parameters, such as a treatment’s effect on multiple outcomes, across studies. Univariate meta-analysis (UVMA) considers each parameter individually, while multivariate meta-analysis (MVMA) considers the parameters jointly and accounts for the correlation between their estimates. The performance of MVMA and UVMA has been extensively compared in scenarios with two parameters. Our objective is to compare the performance of MVMA and UVMA as the number of parameters, p, increases. Specifically, we show that (i) for fixed-effect meta-analysis, the benefit from using MVMA can substantially increase as p increases; (ii) for random effects meta-analysis, the benefit from MVMA can increase as p increases, but the potential improvement is modest in the presence of high between-study variability and the actual improvement is further reduced by the need to estimate an increasingly large between study covariance matrix; and (iii) when there is little to no between study variability, the loss of efficiency due to choosing random effects MVMA over fixed-effect MVMA increases as p increases. We demonstrate these three features through theory, simulation, and a meta-analysis of risk factors for Non-Hodgkin Lymphoma. PMID:28195655

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

PubMed

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

Novel Anthropometry Based on 3D-Bodyscans Applied to a Large Population Based Cohort.

PubMed

Löffler-Wirth, Henry; Willscher, Edith; Ahnert, Peter; Wirkner, Kerstin; Engel, Christoph; Loeffler, Markus; Binder, Hans

2016-01-01

Three-dimensional (3D) whole body scanners are increasingly used as precise measuring tools for the rapid quantification of anthropometric measures in epidemiological studies. We analyzed 3D whole body scanning data of nearly 10,000 participants of a cohort collected from the adult population of Leipzig, one of the largest cities in Eastern Germany. We present a novel approach for the systematic analysis of this data which aims at identifying distinguishable clusters of body shapes called body types. In the first step, our method aggregates body measures provided by the scanner into meta-measures, each representing one relevant dimension of the body shape. In a next step, we stratified the cohort into body types and assessed their stability and dependence on the size of the underlying cohort. Using self-organizing maps (SOM) we identified thirteen robust meta-measures and fifteen body types comprising between 1 and 18 percent of the total cohort size. Thirteen of them are virtually gender specific (six for women and seven for men) and thus reflect most abundant body shapes of women and men. Two body types include both women and men, and describe androgynous body shapes that lack typical gender specific features. The body types disentangle a large variability of body shapes enabling distinctions which go beyond the traditional indices such as body mass index, the waist-to-height ratio, the waist-to-hip ratio and the mortality-hazard ABSI-index. In a next step, we will link the identified body types with disease predispositions to study how size and shape of the human body impact health and disease.

A review of wildlife tourism and meta-analysis of parasitism in Africa's national parks and game reserves.

PubMed

Odeniran, Paul Olalekan; Ademola, Isaiah Oluwafemi; Jegede, Henry Olanrewaju

2018-06-14

The recent increase of parasitic diseases associated with wildlife tourism can be traced to human contact with wildlife and intense modification of wildlife habitat. The continental estimates of parasitic diseases among visited wildlife-tourists and mammalian wildlife present in conservation areas are lacking; therefore, a general review was necessary to provide insights into Africa's parasitic disease burden and transmission between humans and wildlife. A two-step analysis was conducted with searches in Ovid MEDLINE, EMBASE, PubMed, Web of Science and Global Health. All diseases reported without prevalence were grouped and analysed as categorical data while meta-analysis of prevalence rates of parasitic diseases in wildlife from national parks and reserves in Africa was conducted. Only 4.7% of the tourist centres reported routine wildlife diagnosis for parasitic diseases. Disease intensity shows that cryptosporidiosis and seven other parasitic diseases were observed in both human and wildlife; however, no significant difference in intensity between human and wildlife hosts was observed. Schistosomiasis intensity reports showed a significant increase (P < 0.05) while entamoebiasis showed a significant decrease (P < 0.05) in humans as compared to wildlife. Visiting tourists were more infected with malaria, while wildlife was more infected with parasitic gastroenteritis (PGE). The meta-analysis of wildlife revealed the highest prevalence of PGE with mixed parasites and lowest prevalence of Giardia spp. at 99.9 and 5.7%, respectively. The zoonotic and socioeconomic impact of some of these parasites could pose a severe public threat to tourism. Pre- and post-travel clinical examinations are important for tourists while routine examination, treatment and rational surveillance are important for these animals to improve wildlife tourism.

Converting from Transdermal to Buccal Formulations of Buprenorphine: A Pharmacokinetic Meta-Model Simulation in Healthy Volunteers.

PubMed

Priestley, Tony; Chappa, Arvind K; Mould, Diane R; Upton, Richard N; Shusterman, Neil; Passik, Steven; Tormo, Vicente J; Camper, Stephen

2017-09-29

 To develop a model to predict buprenorphine plasma concentrations during transition from transdermal to buccal administration.  Population pharmacokinetic model-based meta-analysis of published data.  A model-based meta-analysis of available buprenorphine pharmacokinetic data in healthy adults, extracted as aggregate (mean) data from published literature, was performed to explore potential conversion from transdermal to buccal buprenorphine. The time course of mean buprenorphine plasma concentrations following application of transdermal patch or buccal film was digitized from available literature, and a meta-model was developed using specific pharmacokinetic parameters (e.g., absorption rate, apparent clearance, and volumes of distribution) derived from analysis of pharmacokinetic data for intravenously, transdermally, and buccally administered buprenorphine.  Data from six studies were included in this analysis. The final transdermal absorption model employed a zero-order input rate that was scaled to reflect a nominal patch delivery rate and time after patch application (with decline in rate over time). The transdermal absorption rate constant became zero following patch removal. Buccal absorption was a first-order process with a time lag and bioavailability term. Simulations of conversion from transdermal 20 mcg/h and 10 mcg/h to buccal administration suggest that transition can be made rapidly (beginning 12 hours after patch removal) using the recommended buccal formulation titration increments (75-150 mcg) and schedule (every four days) described in the product labeling.  Computer modeling and simulations using a meta-model built from data extracted from publications suggest that rapid and straightforward conversion from transdermal to buccal buprenorphine is feasible. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Bayesian approach to meta-analysis of plant pathology studies.

PubMed

Mila, A L; Ngugi, H K

2011-01-01

Bayesian statistical methods are used for meta-analysis in many disciplines, including medicine, molecular biology, and engineering, but have not yet been applied for quantitative synthesis of plant pathology studies. In this paper, we illustrate the key concepts of Bayesian statistics and outline the differences between Bayesian and classical (frequentist) methods in the way parameters describing population attributes are considered. We then describe a Bayesian approach to meta-analysis and present a plant pathological example based on studies evaluating the efficacy of plant protection products that induce systemic acquired resistance for the management of fire blight of apple. In a simple random-effects model assuming a normal distribution of effect sizes and no prior information (i.e., a noninformative prior), the results of the Bayesian meta-analysis are similar to those obtained with classical methods. Implementing the same model with a Student's t distribution and a noninformative prior for the effect sizes, instead of a normal distribution, yields similar results for all but acibenzolar-S-methyl (Actigard) which was evaluated only in seven studies in this example. Whereas both the classical (P = 0.28) and the Bayesian analysis with a noninformative prior (95% credibility interval [CRI] for the log response ratio: -0.63 to 0.08) indicate a nonsignificant effect for Actigard, specifying a t distribution resulted in a significant, albeit variable, effect for this product (CRI: -0.73 to -0.10). These results confirm the sensitivity of the analytical outcome (i.e., the posterior distribution) to the choice of prior in Bayesian meta-analyses involving a limited number of studies. We review some pertinent literature on more advanced topics, including modeling of among-study heterogeneity, publication bias, analyses involving a limited number of studies, and methods for dealing with missing data, and show how these issues can be approached in a Bayesian framework. Bayesian meta-analysis can readily include information not easily incorporated in classical methods, and allow for a full evaluation of competing models. Given the power and flexibility of Bayesian methods, we expect them to become widely adopted for meta-analysis of plant pathology studies.

Modelling heterogeneity variances in multiple treatment comparison meta-analysis--are informative priors the better solution?

PubMed

Thorlund, Kristian; Thabane, Lehana; Mills, Edward J

2013-01-11

Multiple treatment comparison (MTC) meta-analyses are commonly modeled in a Bayesian framework, and weakly informative priors are typically preferred to mirror familiar data driven frequentist approaches. Random-effects MTCs have commonly modeled heterogeneity under the assumption that the between-trial variance for all involved treatment comparisons are equal (i.e., the 'common variance' assumption). This approach 'borrows strength' for heterogeneity estimation across treatment comparisons, and thus, ads valuable precision when data is sparse. The homogeneous variance assumption, however, is unrealistic and can severely bias variance estimates. Consequently 95% credible intervals may not retain nominal coverage, and treatment rank probabilities may become distorted. Relaxing the homogeneous variance assumption may be equally problematic due to reduced precision. To regain good precision, moderately informative variance priors or additional mathematical assumptions may be necessary. In this paper we describe four novel approaches to modeling heterogeneity variance - two novel model structures, and two approaches for use of moderately informative variance priors. We examine the relative performance of all approaches in two illustrative MTC data sets. We particularly compare between-study heterogeneity estimates and model fits, treatment effect estimates and 95% credible intervals, and treatment rank probabilities. In both data sets, use of moderately informative variance priors constructed from the pair wise meta-analysis data yielded the best model fit and narrower credible intervals. Imposing consistency equations on variance estimates, assuming variances to be exchangeable, or using empirically informed variance priors also yielded good model fits and narrow credible intervals. The homogeneous variance model yielded high precision at all times, but overall inadequate estimates of between-trial variances. Lastly, treatment rankings were similar among the novel approaches, but considerably different when compared with the homogenous variance approach. MTC models using a homogenous variance structure appear to perform sub-optimally when between-trial variances vary between comparisons. Using informative variance priors, assuming exchangeability or imposing consistency between heterogeneity variances can all ensure sufficiently reliable and realistic heterogeneity estimation, and thus more reliable MTC inferences. All four approaches should be viable candidates for replacing or supplementing the conventional homogeneous variance MTC model, which is currently the most widely used in practice.

Detecting Bias in Meta-Analyses of Distance Education Research: Big Pictures We Can Rely On

ERIC Educational Resources Information Center

Bernard, Robert M.; Borokhovski, Eugene; Tamim, Rana M.

2014-01-01

This article has two interrelated purposes. The first is to explain how various forms of bias, if introduced during any stage of a meta-analysis, can provide the consumer with a misimpression of the state of a research literature. Five of the most important bias-producing aspects of a meta-analysis are presented and discussed. Second, armed with…

Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

PubMed Central

Chen, Brian H.; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J.; Yanek, Lisa R.; Nalls, Michael A.; Comeau, Mary E.; Rasmussen-Torvik, Laura J.; Jensen, Richard A.; Evans, Daniel S.; Sun, Yan V.; An, Ping; Patel, Sanjay R.; Lu, Yingchang; Long, Jirong; Armstrong, Loren L.; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M.; Palmer, Nicholette D.; Mudgal, Poorva; Langefeld, Carl D.; Keene, Keith L.; Freedman, Barry I.; Mychaleckyj, Josyf C.; Nayak, Uma; Raffel, Leslie J.; Goodarzi, Mark O.; Chen, Y-D Ida; Taylor, Herman A.; Correa, Adolfo; Sims, Mario; Couper, David; Pankow, James S.; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A.; Vaidya, Dhananjay; Singleton, Andrew B.; Zonderman, Alan B.; Igo, Robert P.; Sedor, John R.; Kabagambe, Edmond K.; Siscovick, David S.; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F.; Kraja, Aldi; Province, Michael A.; Bottinger, Erwin P.; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J.; Lowe, William L.; Pacheco, Jennifer A.; Crawford, Dana C.; Grundberg, Elin; Rich, Stephen S.; Hayes, M. Geoffrey; Shu, Xiao-Ou; Loos, Ruth J. F.; Borecki, Ingrid B.; Peyser, Patricia A.; Cummings, Steven R.; Psaty, Bruce M.; Fornage, Myriam; Iyengar, Sudha K.; Evans, Michele K.; Becker, Diane M.; Kao, W. H. Linda; Wilson, James G.; Rotter, Jerome I.; Sale, Michèle M.; Liu, Simin; Rotimi, Charles N.; Bowden, Donald W.

2014-01-01

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94

Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

PubMed

Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J; Yanek, Lisa R; Nalls, Michael A; Comeau, Mary E; Rasmussen-Torvik, Laura J; Jensen, Richard A; Evans, Daniel S; Sun, Yan V; An, Ping; Patel, Sanjay R; Lu, Yingchang; Long, Jirong; Armstrong, Loren L; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M; Palmer, Nicholette D; Mudgal, Poorva; Langefeld, Carl D; Keene, Keith L; Freedman, Barry I; Mychaleckyj, Josyf C; Nayak, Uma; Raffel, Leslie J; Goodarzi, Mark O; Chen, Y-D Ida; Taylor, Herman A; Correa, Adolfo; Sims, Mario; Couper, David; Pankow, James S; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A; Vaidya, Dhananjay; Singleton, Andrew B; Zonderman, Alan B; Igo, Robert P; Sedor, John R; Kabagambe, Edmond K; Siscovick, David S; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F; Kraja, Aldi; Province, Michael A; Bottinger, Erwin P; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J; Lowe, William L; Pacheco, Jennifer A; Crawford, Dana C; Grundberg, Elin; Rich, Stephen S; Hayes, M Geoffrey; Shu, Xiao-Ou; Loos, Ruth J F; Borecki, Ingrid B; Peyser, Patricia A; Cummings, Steven R; Psaty, Bruce M; Fornage, Myriam; Iyengar, Sudha K; Evans, Michele K; Becker, Diane M; Kao, W H Linda; Wilson, James G; Rotter, Jerome I; Sale, Michèle M; Liu, Simin; Rotimi, Charles N; Bowden, Donald W

2014-08-01

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)

dbMDEGA: a database for meta-analysis of differentially expressed genes in autism spectrum disorder.

PubMed

Zhang, Shuyun; Deng, Libin; Jia, Qiyue; Huang, Shaoting; Gu, Junwang; Zhou, Fankun; Gao, Meng; Sun, Xinyi; Feng, Chang; Fan, Guangqin

2017-11-16

Autism spectrum disorders (ASD) are hereditary, heterogeneous and biologically complex neurodevelopmental disorders. Individual studies on gene expression in ASD cannot provide clear consensus conclusions. Therefore, a systematic review to synthesize the current findings from brain tissues and a search tool to share the meta-analysis results are urgently needed. Here, we conducted a meta-analysis of brain gene expression profiles in the current reported human ASD expression datasets (with 84 frozen male cortex samples, 17 female cortex samples, 32 cerebellum samples and 4 formalin fixed samples) and knock-out mouse ASD model expression datasets (with 80 collective brain samples). Then, we applied R language software and developed an interactive shared and updated database (dbMDEGA) displaying the results of meta-analysis of data from ASD studies regarding differentially expressed genes (DEGs) in the brain. This database, dbMDEGA ( https://dbmdega.shinyapps.io/dbMDEGA/ ), is a publicly available web-portal for manual annotation and visualization of DEGs in the brain from data from ASD studies. This database uniquely presents meta-analysis values and homologous forest plots of DEGs in brain tissues. Gene entries are annotated with meta-values, statistical values and forest plots of DEGs in brain samples. This database aims to provide searchable meta-analysis results based on the current reported brain gene expression datasets of ASD to help detect candidate genes underlying this disorder. This new analytical tool may provide valuable assistance in the discovery of DEGs and the elucidation of the molecular pathogenicity of ASD. This database model may be replicated to study other disorders.

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

PubMed

Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Associations of health literacy with diabetic foot outcomes: a systematic review and meta-analysis.

PubMed

Chen, P Y; Elmer, S; Callisaya, M; Wills, K; Greenaway, T M; Winzenberg, T M

2018-05-26

People with diabetes have low health literacy, but the role of the latter in diabetic foot disease is unclear. To determine, through a systematic review and meta-analysis, if health literacy is associated with diabetic foot disease, its risk factors, or foot care. We searched PubMed, EMBASE, CINAHL, Web of Science, Scopus and Science Direct. All studies were screened and data extracted by two independent reviewers. Studies in English with valid and reliable measures of health literacy and published tests of association were included. Data were extracted on the associations between the outcomes and health literacy. Meta-analyses were performed using random effects models. Sixteen articles were included in the systematic review, with 11 in the meta-analysis. In people with inadequate health literacy, the odds of having diabetic foot disease were twice those in people with adequate health literacy, but this was not statistically significant [odds ratio 1.99 (95% CI 0.83, 4.78); two studies in 1278 participants]. There was no statistically significant difference in health literacy levels between people with and without peripheral neuropathy [standardized mean difference -0.14 (95% CI -0.47, 0.18); two studies in 399 participants]. There was no association between health literacy and foot care [correlation coefficient 0.01 (95% CI -0.07, 0.10); seven studies in 1033 participants]. There were insufficient data to exclude associations between health literacy and diabetic foot disease and its risk factors, but health literacy appears unlikely to have a role in foot care. The contribution of low health literacy to diabetic foot disease requires definitive assessment through robust longitudinal studies. © 2018 Diabetes UK.

Project INTEGRATE: An Integrative Study of Brief Alcohol Interventions for College Students

PubMed Central

Mun, Eun-Young; de la Torre, Jimmy; Atkins, David C.; White, Helene R.; Ray, Anne E.; Kim, Su-Young; Jiao, Yang; Clarke, Nickeisha; Huo, Yan; Larimer, Mary E.; Huh, David

2014-01-01

This paper provides an overview of a study that synthesizes multiple, independently collected alcohol intervention studies for college students into a single, multisite longitudinal data set. This research embraced innovative analytic strategies (i.e., integrative data analysis or meta-analysis using individual participant-level data), with the overall goal of answering research questions that are difficult to address in individual studies such as moderation analysis, while providing a built-in replication for the reported efficacy of brief motivational interventions for college students. Data were pooled across 24 intervention studies, of which 21 included a comparison or control condition and all included one or more treatment conditions. This yielded a sample of 12,630 participants (42% men; 58% first-year or incoming students). The majority of the sample identified as White (74%), with 12% Asian, 7% Hispanic, 2% Black, and 5% other/mixed ethnic groups. Participants were assessed two or more times from baseline up to 12 months, with varying assessment schedules across studies. This paper describes how we combined individual participant-level data from multiple studies, and discusses the steps taken to develop commensurate measures across studies via harmonization and newly developed Markov chain Monte Carlo algorithms for two-parameter logistic item response theory models and a generalized partial credit model. This innovative approach has intriguing promises, but significant barriers exist. To lower the barriers, there is a need to increase overlap in measures and timing of follow-up assessments across studies, better define treatment and control groups, and improve transparency and documentation in future single, intervention studies. PMID:25546144

Kinetic analysis of overlapping multistep thermal decomposition comprising exothermic and endothermic processes: thermolysis of ammonium dinitramide.

PubMed

Muravyev, Nikita V; Koga, Nobuyoshi; Meerov, Dmitry B; Pivkina, Alla N

2017-01-25

This study focused on kinetic modeling of a specific type of multistep heterogeneous reaction comprising exothermic and endothermic reaction steps, as exemplified by the practical kinetic analysis of the experimental kinetic curves for the thermal decomposition of molten ammonium dinitramide (ADN). It is known that the thermal decomposition of ADN occurs as a consecutive two step mass-loss process comprising the decomposition of ADN and subsequent evaporation/decomposition of in situ generated ammonium nitrate. These reaction steps provide exothermic and endothermic contributions, respectively, to the overall thermal effect. The overall reaction process was deconvoluted into two reaction steps using simultaneously recorded thermogravimetry and differential scanning calorimetry (TG-DSC) curves by considering the different physical meanings of the kinetic data derived from TG and DSC by P value analysis. The kinetic data thus separated into exothermic and endothermic reaction steps were kinetically characterized using kinetic computation methods including isoconversional method, combined kinetic analysis, and master plot method. The overall kinetic behavior was reproduced as the sum of the kinetic equations for each reaction step considering the contributions to the rate data derived from TG and DSC. During reproduction of the kinetic behavior, the kinetic parameters and contributions of each reaction step were optimized using kinetic deconvolution analysis. As a result, the thermal decomposition of ADN was successfully modeled as partially overlapping exothermic and endothermic reaction steps. The logic of the kinetic modeling was critically examined, and the practical usefulness of phenomenological modeling for the thermal decomposition of ADN was illustrated to demonstrate the validity of the methodology and its applicability to similar complex reaction processes.

Treatment of vaginal candidiasis for the prevention of preterm birth: a systematic review and meta-analysis.

PubMed

Roberts, Christine L; Algert, Charles S; Rickard, Kristen L; Morris, Jonathan M

2015-03-21

Recognition that ascending infection leads to preterm birth has led to a number of studies that have evaluated the treatment of vaginal infections in pregnancy to reduce preterm birth rates. However, the role of candidiasis is relatively unexplored. Our aim was to undertake a systematic review and meta-analysis to assess whether treatment of pregnant women with vulvovaginal candidiasis reduces preterm birth rates and other adverse birth outcomes. We undertook a systematic review and meta-analysis of published randomised controlled trials (RCTs) in which pregnant women were treated for vulvovaginal candidiasis (compared to placebo or no treatment) and where preterm birth was reported as an outcome. Trials were identified by searching the Cochrane Central Register of Controlled Trials, Medline and Embase databases to January 2014. Trial eligibility and outcomes were pre-specified. Two reviewers independently assessed the studies against the agreed criteria and extracted relevant data using a standard data extraction form. Meta-analysis was used to calculate pooled rate ratios (RR) and 95% confidence intervals (CI) using a fixed-effects model. There were two eligible RCTs both among women with asymptomatic candidiasis, with a total of 685 women randomised. Both trials compared treatment with usual care (no screening for, or treatment of, asymptomatic candidiasis). Data from one trial involved a post-hoc subgroup analysis (n = 586) of a larger trial of treatment of 4,429 women with asymptomatic infections in pregnancy and the other was a pilot study (n = 99). There was a significant reduction in spontaneous preterm births in treated compared with untreated women (meta-analysis RR = 0.36, 95% CI = 0.17 to 0.75). Other outcomes were reported by one or neither trial. This systematic review found two trials comparing the treatment of asymptomatic vaginal candidiasis in pregnancy for the outcome of preterm birth. Although the effect estimate suggests that treatment of asymptomatic candidiasis may reduce the risk of preterm birth, the result needs to be interpreted with caution as the primary driver for the pooled estimate comes from a post-hoc (unplanned) subgroup analysis. A prospective trial with sufficient power to answer the clinical question 'does treatment of asymptomatic candidiasis in early pregnancy prevent preterm birth' is warranted. PROSPERO CRD42014009241.

Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis

PubMed Central

Li, Zhouna; Jin, Zhehu

2016-01-01

Background Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars. Methods Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis. Results Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions. Conclusion There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to confirm our conclusion. PMID:27877046

Association between methylenetetrahydrofolate reductase polymorphisms and the relapse of acute lymphoblastic leukemia: a meta-analysis.

PubMed

He, H-R; Chen, S-Y; You, H-S; Hu, S-S; Sun, J-Y; Dong, Y-L; Lu, J

2014-10-01

Relapse is a threat in patients treated for acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) activity may affect the sensitivity of patients to folate-based chemotherapeutic drugs, thus influencing the relapse risk. Two polymorphisms of the gene encoding MTHFR, C677T and A1298C, alter MTHFR enzyme activity and may be associated with ALL relapse. The aim of this meta-analysis was to clarify the correlation between the C677T and A1298C polymorphisms and ALL relapse. To this end, data were collected from studies of the association between these two polymorphisms and ALL relapse. Analysis of the data revealed a serious contradiction among the results. A recessive model demonstrated that the ALL relapse risk was significantly increased in carriers of the 677 TT genotype, especially for pediatric ALL, but was unaffected by the A1298C polymorphism. These findings confirm that the MTHFR C677T polymorphism could be considered as a good marker of the pediatric ALL relapse risk.

Accident models for two-lane rural roads : segments and intersections

DOT National Transportation Integrated Search

1998-10-01

This report is a direct step for the implementation of the Accident Analysis Module in the Interactive Highway Safety Design Model (IHSDM). The Accident Analysis Module is expected to estimate the safety of two-lane rural highway characteristics for ...

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

PubMed

Acconcia, M C; Caretta, Q; Romeo, F; Borzi, M; Perrone, M A; Sergi, D; Chiarotti, F; Calabrese, C M; Sili Scavalli, A; Gaudio, C

2018-04-01

Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Permeability and kinetic coefficients for mesoscale BCF surface step dynamics: Discrete two-dimensional deposition-diffusion equation analysis

DOE PAGES

Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.

2016-04-08

Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less

Permeability and kinetic coefficients for mesoscale BCF surface step dynamics: Discrete two-dimensional deposition-diffusion equation analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.

Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less

Serine/threonine kinase 15 gene polymorphism and risk of digestive system cancers: A meta-analysis.

PubMed

Luo, Jianfei; Yan, Ruicheng; Zou, Li

2015-01-01

Previous studies have reported an association between the two coding polymorphisms (91T>A and 169G>A) of the serine/threonine kinase 15 (STK15) gene and the risk of digestive system cancers; however, the results are inconsistent. In the present study, a meta-analysis was carried out to assess the association between the two STK15 polymorphisms and the risk of digestive system cancers. Relevant studies were identified using PubMed, Web of Science, China National Knowledge Infrastructure, WanFang and VIP databases up to February 18, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed or random effects model. A total of 15 case-control studies from 14 publications were included. Of these, 15 studies concerned the 91T>A polymorphism and included 7,619 cases and 7,196 controls and four studies concerned the 161G>A polymorphism and included 826 cases and 713 controls. A significantly increased risk of digestive system cancers was observed for the 91T>A polymorphism (recessive model: OR, 1.19; 95% CI, 1.07-1.31). In subgroup analysis by ethnicity, a significant association was detected in Asian populations (recessive model: OR, 1.21; 95% CI, 1.08-1.36) but not in Caucasian and mixed populations. Stratification by tumor type indicated that the 91T>A polymorphism was associated with an increased risk of esophageal and colorectal cancers under the recessive model (OR, 1.19; 95% CI, 1.03-1.38; and OR, 1.24; 95% CI, 1.04-1.46; respectively); however, no significant association was observed between the 169G>A polymorphism and the risk of digestive system cancers in any of the genetic models. Furthermore, in subgroup analysis by ethnicity, similar results were observed in the Asian and Caucasian populations. The present meta-analysis demonstrated that the STK15 gene 91T>A polymorphism, but not the 169G>A polymorphism, may be a risk factor for digestive system cancers, particularly for esophageal and colorectal cancers.

Association between estrogen receptora gene (ESR1) PvuII (T/C) and XbaI (A/G) polymorphisms and premature ovarian failure risk: evidence from a meta-analysis.

PubMed

He, Meirong; Shu, Jingcheng; Huang, Xing; Tang, Hui

2015-02-01

Genetic factors are important in the pathogenesis of Premature ovarian failure (POF). Notably, estrogen receptor-a (ESR1) has been suggested as a possible candidate gene for POF; however, published studies of ESR1 gene polymorphisms have been hampered by small sample sizes and inconclusive or ambiguous results. The aim of this meta analysis is to investigate the associations between two novel common ESR1 polymorphisms (intron 1 polymorphisms PvuII-rs2234693: T.C and XbaI-rs9340799: A.G) and POF. A comprehensive search was conducted to identify all studies on the association of ESR1 gene polymorphisms with POF up to August 2014. Pooled odds ratio (OR) and corresponding 95 % confidence interval (CI) were calculated using fixed-or random-effects model in the meta-analysis. Three studies covering 1396 subjects were identified. Pooled data showed significant association between ESR1 gene PvuII polymorphism and risk of POF: [allele model: Cvs. T, OR = 0.735, 95%CI: 0.624 ~ 0.865, p = 0.001; co-dominant models: CCvs.TT, OR = 0.540, 95%CI: 0.382 ~ 0.764, p = 0.001, CTvs.TT, OR = 0.735, 95%CI: 0.555 ~ 0.972, p = 0.031; dominant model: CT + CCvs.TT, OR = 0.618, 95%CI: 0.396 ~ 0.966, p = 0.035; recessive model: CCvs.TT + CT, OR = 0.659, 95%CI: 0.502 ~ 0.864, p = 0.003]. Subgroup analyses showed a significant association in all models in Asian population, but no significant association in any model in European population. For the XbaI polymorphism, overall, no significant association was observed under any genetic models. However, under dominant model, ESR1 gene XbaI polymorphism is significantly association with risk of POF in Asian population. The present meta-analysis suggests that ESR1gene PvuII polymorphism is significantly associated with an increased risk of POF. And ESR1gene XbaI polymorphism is not association with risk of POF overall. However, under dominant model, ESR1gene XbaI polymorphism is significantly association with risk of POF in Asian population. Further large and well-designed studies are needed to confirm the association.

A framework for the meta-analysis of Bland-Altman studies based on a limits of agreement approach.

PubMed

Tipton, Elizabeth; Shuster, Jonathan

2017-10-15

Bland-Altman method comparison studies are common in the medical sciences and are used to compare a new measure to a gold-standard (often costlier or more invasive) measure. The distribution of these differences is summarized by two statistics, the 'bias' and standard deviation, and these measures are combined to provide estimates of the limits of agreement (LoA). When these LoA are within the bounds of clinically insignificant differences, the new non-invasive measure is preferred. Very often, multiple Bland-Altman studies have been conducted comparing the same two measures, and random-effects meta-analysis provides a means to pool these estimates. We provide a framework for the meta-analysis of Bland-Altman studies, including methods for estimating the LoA and measures of uncertainty (i.e., confidence intervals). Importantly, these LoA are likely to be wider than those typically reported in Bland-Altman meta-analyses. Frequently, Bland-Altman studies report results based on repeated measures designs but do not properly adjust for this design in the analysis. Meta-analyses of Bland-Altman studies frequently exclude these studies for this reason. We provide a meta-analytic approach that allows inclusion of estimates from these studies. This includes adjustments to the estimate of the standard deviation and a method for pooling the estimates based upon robust variance estimation. An example is included based on a previously published meta-analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Association between Toll-like receptor 4 Asp299Gly polymorphism and coronary heart disease susceptibility.

PubMed

Wu, B W; Zhu, J; Shi, H M; Jin, B; Wen, Z C

2017-08-07

Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.

Chlorhexidine mouthwash reduces plaque and gingivitis.

PubMed

Herrera, David

2013-03-01

Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched along with the reference lists of all selected studies. Only English language studies were included. Randomised controlled clinical trials comparing chlorhexidine (CHX) to placebo/control mouthrinses for oral hygiene in studies of at least four weeks duration were included. Screening, selection and data abstractions were conducted independently by two reviewers. Where possible meta-analysis of weighted mean differences was carried out using fixed or random effects models where appropriate. Thirty studies were included, with 13 studies contributing to the meta-analysis. The meta-analysis found significant differences favouring CHX for a range of indices; the Plaque Index Silness & Löe, Plaque-Index Quigley & Hein (PIQH), the Gingival Index (GI), Papillary BIeeding Index, Bleeding on Marginal Probing and the Lobene Stain Index. Relative to control, the reduction with CHX for plaque was 33% and for gingivitis 26%. CHX rinsing groups demonstrated significantly more staining. In gingivitis patients, CHX mouthrinses together with OH versus placebo, or control mouthrinse provide significant reductions in plaque and gingivitis scores, but a significant increase in staining score.

Comparisons of Fatty Acid Taste Detection Thresholds in People Who Are Lean vs. Overweight or Obese: A Systematic Review and Meta-Analysis.

PubMed

Tucker, Robin M; Kaiser, Kathryn A; Parman, Mariel A; George, Brandon J; Allison, David B; Mattes, Richard D

2017-01-01

Given the increasing evidence that supports the ability of humans to taste non-esterified fatty acids (NEFA), recent studies have sought to determine if relationships exist between oral sensitivity to NEFA (measured as thresholds), food intake and obesity. Published findings suggest there is either no association or an inverse association. A systematic review and meta-analysis was conducted to determine if differences in fatty acid taste sensitivity or intensity ratings exist between individuals who are lean or obese. A total of 7 studies that reported measurement of taste sensations to non-esterified fatty acids by psychophysical methods (e.g.,studies using model systems rather than foods, detection thresholds as measured by a 3-alternative forced choice ascending methodology were included in the meta-analysis. Two other studies that measured intensity ratings to graded suprathreshold NEFA concentrations were evaluated qualitatively. No significant differences in fatty acid taste thresholds or intensity were observed. Thus, differences in fatty acid taste sensitivity do not appear to precede or result from obesity.

Using meta-analysis to inform the design of subsequent studies of diagnostic test accuracy.

PubMed

Hinchliffe, Sally R; Crowther, Michael J; Phillips, Robert S; Sutton, Alex J

2013-06-01

An individual diagnostic accuracy study rarely provides enough information to make conclusive recommendations about the accuracy of a diagnostic test; particularly when the study is small. Meta-analysis methods provide a way of combining information from multiple studies, reducing uncertainty in the result and hopefully providing substantial evidence to underpin reliable clinical decision-making. Very few investigators consider any sample size calculations when designing a new diagnostic accuracy study. However, it is important to consider the number of subjects in a new study in order to achieve a precise measure of accuracy. Sutton et al. have suggested previously that when designing a new therapeutic trial, it could be more beneficial to consider the power of the updated meta-analysis including the new trial rather than of the new trial itself. The methodology involves simulating new studies for a range of sample sizes and estimating the power of the updated meta-analysis with each new study added. Plotting the power values against the range of sample sizes allows the clinician to make an informed decision about the sample size of a new trial. This paper extends this approach from the trial setting and applies it to diagnostic accuracy studies. Several meta-analytic models are considered including bivariate random effects meta-analysis that models the correlation between sensitivity and specificity. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Meta-analysis of sex-specific genome-wide association studies.

PubMed

Magi, Reedik; Lindgren, Cecilia M; Morris, Andrew P

2010-12-01

Despite the success of genome-wide association studies, much of the genetic contribution to complex human traits is still unexplained. One potential source of genetic variation that may contribute to this "missing heritability" is that which differs in magnitude and/or direction between males and females, which could result from sexual dimorphism in gene expression. Such sex-differentiated effects are common in model organisms, and are becoming increasingly evident in human complex traits through large-scale male- and female-specific meta-analyses. In this article, we review the methodology for meta-analysis of sex-specific genome-wide association studies, and propose a sex-differentiated test of association with quantitative or dichotomous traits, which allows for heterogeneity of allelic effects between males and females. We perform detailed simulations to compare the power of the proposed sex-differentiated meta-analysis with the more traditional "sex-combined" approach, which is ambivalent to gender. The results of this study highlight only a small loss in power for the sex-differentiated meta-analysis when the allelic effects of the causal variant are the same in males and females. However, over a range of models of heterogeneity in allelic effects between genders, our sex-differentiated meta-analysis strategy offers substantial gains in power, and thus has the potential to discover novel loci contributing effects to complex human traits with existing genome-wide association data. © 2010 Wiley-Liss, Inc.

Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis

PubMed Central

Kim, Su Kang; Kang, Sang Wook; Chung, Joo-Ho; Park, Hae Jeong; Cho, Kyu Bong; Park, Min-Su

2015-01-01

The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025–1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. PMID:26295386

Meta-analysis of the efficacy of psychological and educational interventions to improve academic performance of students with learning disabilities in Iran

PubMed Central

Faramarzi, Salar; Shamsi, Abdolhossein; Samadi, Maryam; Ahmadzade, Maryam

2015-01-01

Introduction: with due attention to the importance of learning disabilities and necessity of presenting interventions for improvement of these disorders in order to prevent future problems, this study used meta-analysis of the research model on the impact of psychological and educational interventions to improve academic performance of students with learning disabilities. Methods: with the use of meta-analysis method by integrating the results of various researches, this study specifies the effect of psychological and educational interventions. In this order, 57 studies, which their methodology was accepted, were selected and meta-analysis was performed on them. The research instrument was a meta-analysis checklist. Results: The effect size for the effectiveness of psychological-educational interventions on improving the academic performance of students with mathematics disorder (0.57), impaired writing (0.50) and dyslexia (0.55) were reported. Conclusions: The result of meta-analysis showed that according to Cohen's table, the effect size is above average, and it can be said that educational and psychological interventions improve the academic performance of students with learning disabilities. PMID:26430685

Limitations in Using Multiple Imputation to Harmonize Individual Participant Data for Meta-Analysis.

PubMed

Siddique, Juned; de Chavez, Peter J; Howe, George; Cruden, Gracelyn; Brown, C Hendricks

2018-02-01

Individual participant data (IPD) meta-analysis is a meta-analysis in which the individual-level data for each study are obtained and used for synthesis. A common challenge in IPD meta-analysis is when variables of interest are measured differently in different studies. The term harmonization has been coined to describe the procedure of placing variables on the same scale in order to permit pooling of data from a large number of studies. Using data from an IPD meta-analysis of 19 adolescent depression trials, we describe a multiple imputation approach for harmonizing 10 depression measures across the 19 trials by treating those depression measures that were not used in a study as missing data. We then apply diagnostics to address the fit of our imputation model. Even after reducing the scale of our application, we were still unable to produce accurate imputations of the missing values. We describe those features of the data that made it difficult to harmonize the depression measures and provide some guidelines for using multiple imputation for harmonization in IPD meta-analysis.

Meta-analysis of the efficacy of psychological and educational interventions to improve academic performance of students with learning disabilities in Iran.

PubMed

Faramarzi, Salar; Shamsi, Abdolhossein; Samadi, Maryam; Ahmadzade, Maryam

2015-01-01

with due attention to the importance of learning disabilities and necessity of presenting interventions for improvement of these disorders in order to prevent future problems, this study used meta-analysis of the research model on the impact of psychological and educational interventions to improve academic performance of students with learning disabilities. with the use of meta-analysis method by integrating the results of various researches, this study specifies the effect of psychological and educational interventions. In this order, 57 studies, which their methodology was accepted, were selected and meta-analysis was performed on them. The research instrument was a meta-analysis checklist. The effect size for the effectiveness of psychological-educational interventions on improving the academic performance of students with mathematics disorder (0.57), impaired writing (0.50) and dyslexia (0.55) were reported. The result of meta-analysis showed that according to Cohen's table, the effect size is above average, and it can be said that educational and psychological interventions improve the academic performance of students with learning disabilities.

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas

PubMed Central

Parra, E. J.; Below, J. E.; Krithika, S.; Valladares, A.; Barta, J. L.; Cox, N. J.; Hanis, C. L.; Wacher, N.; Garcia-Mena, J.; Hu, P.; Shriver, M. D.; Kumate, J.; McKeigue, P. M.; Escobedo, J.; Cruz, M.

2013-01-01

Aims/hypothesis We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. Methods We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. Results In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p<10−5) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p<5×10−8) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. Conclusions/interpretation We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes. PMID:21573907

Systemic Oxidative Stress Biomarkers in Chronic Periodontitis: A Meta-Analysis

PubMed Central

Liu, Zhiqiang; Liu, Yan; Song, Yiqing; Zhang, Xi; Wang, Songlin; Wang, Zuomin

2014-01-01

Oxidative stress biomarkers have been observed in peripheral blood of chronic periodontitis patients; however, their associations with periodontitis were not consistent. This meta-analysis was performed to clarify the associations between chronic periodontitis and oxidative biomarkers in systemic circulation. Electronic searches of PubMed and Embase databases were performed until October 2014 and articles were selected to meet inclusion criteria. Data of oxidative biomarkers levels in peripheral blood of periodontitis patients and periodontal healthy controls were extracted to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) by using random-effects model. Of 31 eligible articles, 16 articles with available data were included in meta-analysis. Our results showed that periodontitis patients had significantly lower levels of total antioxidant capacity (SMD = −2.02; 95% CI: −3.08, −0.96; P = 0.000) and higher levels of malondialdehyde (SMD = 0.99; 95% CI: 0.12, 1.86; P = 0.026) and nitric oxide (SMD = 4.98; 95% CI: 2.33, 7.63; P = 0.000) than periodontal healthy control. Superoxide dismutase levels between two groups were not significantly different (SMD = −1.72; 95% CI: −3.50, 0.07; P = 0.059). In conclusion, our meta-analysis showed that chronic periodontitis is significantly associated with circulating levels of three oxidative stress biomarkers, indicating a role of chronic periodontitis in systemic diseases. PMID:25477703

Risk factors for Pseudomonas aeruginosa infections consequences of inappropriate initial antimicrobial therapy: a systematic literature review meta-analysis.

PubMed

Merchant, Sanjay; Proudfoot, Emma M; Quadri, Hafsa N; McElroy, Heather J; Wright, William R; Gupta, Ankur; Sarpong, Eric M

2018-02-15

Treating infections of Gram-negative pathogens, in particular Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region due to inherent and acquired resistance to antimicrobials. This systematic review and meta-analysis provides updated information of the risk factors for P. aeruginosa infections in Asia-Pacific, and consequences (e.g., mortality, costs) of initial inappropriate antimicrobial therapy (IIAT). EMBASE and MEDLINE databases were searched for Asia-Pacific studies reporting the consequences of IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative infections, and risk factors for serious P. aeruginosa infections. A meta-analysis of unadjusted mortality was performed using random-effects model. Twenty-two studies reporting mortality and 13 reporting risk factors were identified. The meta-analysis demonstrated that mortality was significantly lower in patients receiving IAAT versus IIAT, with 67% reduction observed for 28- or 30-day all-cause mortality (OR 0.33; 95% CI 0.20, 0.55; P <0.001). Risk factors for serious P. aeruginosa infection include previous exposure to antimicrobials, mechanical ventilation, and previous hospitalization. The high rates of antimicrobial resistance in Asia-Pacific, as well as increased mortality associated with IIAT and the presence of risk factors for serious infection, highlight the importance of access to newer and appropriate antimicrobials. Copyright © 2018. Published by Elsevier Ltd.

Adjunctive Corticosteroids for Pneumocystis jirovecii Pneumonia in Non-HIV-infected Patients: A Systematic Review and Meta-analysis of Observational Studies.

PubMed

Fujikura, Yuji; Manabe, Toshie; Kawana, Akihiko; Kohno, Shigeru

2017-02-01

The clinical benefits of adjunctive corticosteroids for Pneumocystis jirovecii (P. jirovecii) pneumonia in patients not infected with the human immunodeficiency virus (HIV) has not been evaluated by meta-analysis. We conducted a systematic review of published studies describing the effects of adjunctive corticosteroids on outcome in non-HIV P. jirovecii pneumonia patients. Two investigators independently searched the PubMed and Cochrane databases for eligible articles written in English. A meta-analysis was performed using a random-effects model for measuring mortality as the primary outcome, and the need for intubation or mechanical ventilation as the secondary outcome. Seven observational studies were eligible. In these studies, adjunctive corticosteroids did not affect mortality in non-HIV patients (odds ratio [OR] 1.26; 95% CI 0.60-2.67) and there was no beneficial effect in patients with severe hypoxemia (PaO 2 <70mmHg) (OR 0.90; 95% CI 0.44-1.83). No significant effect on the secondary outcome was observed (OR 1.34; 95% CI 0.44-4.11). Although the studies were observational, meta-analysis showed that adjunctive corticosteroids did not improve the outcome of P. jirovecii pneumonia in non-HIV patients. The results warrant a randomized controlled trial. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Robustness of meta-analyses in finding gene × environment interactions

PubMed Central

Shi, Gang; Nehorai, Arye

2017-01-01

Meta-analyses that synthesize statistical evidence across studies have become important analytical tools for genetic studies. Inspired by the success of genome-wide association studies of the genetic main effect, researchers are searching for gene × environment interactions. Confounders are routinely included in the genome-wide gene × environment interaction analysis as covariates; however, this does not control for any confounding effects on the results if covariate × environment interactions are present. We carried out simulation studies to evaluate the robustness to the covariate × environment confounder for meta-regression and joint meta-analysis, which are two commonly used meta-analysis methods for testing the gene × environment interaction or the genetic main effect and interaction jointly. Here we show that meta-regression is robust to the covariate × environment confounder while joint meta-analysis is subject to the confounding effect with inflated type I error rates. Given vast sample sizes employed in genome-wide gene × environment interaction studies, non-significant covariate × environment interactions at the study level could substantially elevate the type I error rate at the consortium level. When covariate × environment confounders are present, type I errors can be controlled in joint meta-analysis by including the covariate × environment terms in the analysis at the study level. Alternatively, meta-regression can be applied, which is robust to potential covariate × environment confounders. PMID:28362796

The association between COMT Val158Met polymorphism and migraine risk: A meta-analysis.

PubMed

Liao, Yao-Jun; Jiang, Jing-Ru; Jin, San-Qing

2017-05-01

Background The COMT Val158Met polymorphism has long been regarded as a risk factor for migraine. The possible association between COMT Val158Met polymorphism and migraine has been evaluated in several studies, but the results are not consistent. Therefore, we conduct this meta-analysis to address these issues. Methods The WEB OF SCIENCE and EMBASE databases were searched for eligible studies. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to estimate the strength of the association between COMT Val158Met polymorphism and migraine. Results Five studies with 979 cases and 1870 controls were ultimately included in the present meta-analysis. The overall data showed no significant association between COMT Val158Met polymorphism and migraine in the multiplicative model (OR = 0.97, 95% CI: 0.78-1.21, p = 0.805) and dominant model (OR = 1.05, 95% CI: 0.75-1.48, p = 0.773), neither in the additive model (OR = 0.97, 95% CI: 0.77-1.23, p = 0.817) nor in the recessive model (OR = 0.88, 95% CI: 0.71-1.09, p = 0.246). In subgroup analysis, both for Caucasian and Asian populations, no statistically significant associations were observed in any genetic models. Conclusions Our meta-analysis suggested that the COMT Val158Met polymorphism was not associated with migraine risk.

Stability of person ability measures in people with acquired brain injury in the use of everyday technology: the test-retest reliability of the Management of Everyday Technology Assessment (META).

PubMed

Malinowsky, Camilla; Kassberg, Ann-Charlotte; Larsson-Lund, Maria; Kottorp, Anders

2016-01-01

To evaluate the test-retest reliability of the Management of Everyday Technology Assessment (META) in a sample of people with acquired brain injury (ABI). The META was administered twice within a two-week period to 25 people with ABI. A Rasch measurement model was used to convert the META ordinal raw scores into equal-interval linear measures of each participant's ability to manage everyday technology (ET). Test-retest reliability of the stability of the person ability measures in the META was examined by a standardized difference Z-test and an intra-class correlations analysis (ICC 1). The results showed that the paired person ability measures generated from the META were stable over the test-retest period for 22 of the 25 subjects. The ICC 1 correlation was 0.63, which indicates good overall reliability. The META demonstrated acceptable test-retest reliability in a sample of people with ABI. The results illustrate the importance of using sufficiently challenging ETs (relative to a person's abilities) to generate stable META measurements over time. Implications for Rehabilitation The findings add evidence regarding the test-retest reliability of the person ability measures generated from the observation assessment META in a sample of people with ABI. The META might support professionals in the evaluation of interventions that are designed to improve clients' performance of activities including the ability to manage ET.

SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta-analysis.

PubMed

Soleimani, Robabeh; Salehi, Zivar; Soltanipour, Soheil; Hasandokht, Tolou; Jalali, Mir Mohammad

2018-04-01

Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta-analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta-analysis was conducted using a random-effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta-regression were performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta-analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: -0.43). In the meta-regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta-analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended. © 2017 Wiley Periodicals, Inc.

The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis.

PubMed

Kapoula, Georgia V; Kontou, Panagiota I; Bagos, Pantelis G

2017-10-26

Pneumatic tube system (PTS) is a widely used method of transporting blood samples in hospitals. The aim of this study was to evaluate the effects of the PTS transport in certain routine laboratory parameters as it has been implicated with hemolysis. A systematic review and a meta-analysis were conducted. PubMed and Scopus databases were searched (up until November 2016) to identify prospective studies evaluating the impact of PTS transport in hematological, biochemical and coagulation measurements. The random-effects model was used in the meta-analysis utilizing the mean difference (MD). Heterogeneity was quantitatively assessed using the Cohran's Q and the I2 index. Subgroup analysis, meta-regression analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed for all outcomes. From a total of 282 studies identified by the searching procedure, 24 were finally included in the meta-analysis. The meta-analysis yielded statistically significant results for potassium (K) [MD=0.04 mmol/L; 95% confidence interval (CI)=0.015-0.065; p=0.002], lactate dehydrogenase (LDH) (MD=10.343 U/L; 95% CI=6.132-14.554; p<10-4) and aspartate aminotransferase (AST) (MD=1.023 IU/L; 95% CI=0.344-1.702; p=0.003). Subgroup analysis and random-effects meta-regression analysis according to the speed and distance of the samples traveled via the PTS revealed that there is relation between the rate and the distance of PTS with the measurements of K, LDH, white blood cells and red blood cells. This meta-analysis suggests that PTS may be associated with alterations in K, LDH and AST measurements. Although these findings may not have any significant clinical effect on laboratory results, it is wise that each hospital validates their PTS.

The Effect of Learning Cycle Models on Achievement of Students: A Meta-Analysis Study

ERIC Educational Resources Information Center

Sarac, Hakan

2018-01-01

In the study, a meta-analysis was conducted to determine the effect of the use of the learning cycle model on the achievements of the students. Doctorate and master theses, made between 2007 and 2016, were searched using the keywords in Turkish and English. As a result of the screening, a total of 123 dissertations, which used learning cycle…

A Comprehensive Meta-Analysis of Triple P-Positive Parenting Program Using Hierarchical Linear Modeling: Effectiveness and Moderating Variables

ERIC Educational Resources Information Center

Nowak, Christoph; Heinrichs, Nina

2008-01-01

A meta-analysis encompassing all studies evaluating the impact of the Triple P-Positive Parenting Program on parent and child outcome measures was conducted in an effort to identify variables that moderate the program's effectiveness. Hierarchical linear models (HLM) with three levels of data were employed to analyze effect sizes. The results (N =…

Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis.

PubMed

Furukawa, Toshi A; Schramm, Elisabeth; Weitz, Erica S; Salanti, Georgia; Efthimiou, Orestis; Michalak, Johannes; Watanabe, Norio; Cipriani, Andrea; Keller, Martin B; Kocsis, James H; Klein, Daniel N; Cuijpers, Pim

2016-05-04

Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. CRD42016035886. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

MetaDP: a comprehensive web server for disease prediction of 16S rRNA metagenomic datasets.

PubMed

Xu, Xilin; Wu, Aiping; Zhang, Xinlei; Su, Mingming; Jiang, Taijiao; Yuan, Zhe-Ming

2016-01-01

High-throughput sequencing-based metagenomics has garnered considerable interest in recent years. Numerous methods and tools have been developed for the analysis of metagenomic data. However, it is still a daunting task to install a large number of tools and complete a complicated analysis, especially for researchers with minimal bioinformatics backgrounds. To address this problem, we constructed an automated software named MetaDP for 16S rRNA sequencing data analysis, including data quality control, operational taxonomic unit clustering, diversity analysis, and disease risk prediction modeling. Furthermore, a support vector machine-based prediction model for intestinal bowel syndrome (IBS) was built by applying MetaDP to microbial 16S sequencing data from 108 children. The success of the IBS prediction model suggests that the platform may also be applied to other diseases related to gut microbes, such as obesity, metabolic syndrome, or intestinal cancer, among others (http://metadp.cn:7001/).

The computational analysis and modelling of substitution effects on hydrolysis of formanilides in acidic aqueous solutions

NASA Astrophysics Data System (ADS)

Lukeš, Vladimír; Škorňa, Peter; Michalík, Martin; Klein, Erik

2017-11-01

Various para, meta and ortho substituted formanilides have been theoretically studied. For trans and cis-isomers of non-substituted formanilide, the calculated B3LYP vibration normal modes were analyzed. Substituent effect on the selected normal modes was described and the comparison with the available experimental data is presented. The calculated B3LYP proton affinities were correlated with Hammett constants, Fujita-Nishioka equation and the rate constants of the hydrolysis in 1 M HCl. Found linear dependences allow predictions of dissociation constants (pKBH+) and hydrolysis rate constants. Obtained results indicate that protonation of amide group may represent the rate determining step of acid catalyzed hydrolysis.

Unmasking the masked Universe: the 2M++ catalogue through Bayesian eyes

NASA Astrophysics Data System (ADS)

Lavaux, Guilhem; Jasche, Jens

2016-01-01

This work describes a full Bayesian analysis of the Nearby Universe as traced by galaxies of the 2M++ survey. The analysis is run in two sequential steps. The first step self-consistently derives the luminosity-dependent galaxy biases, the power spectrum of matter fluctuations and matter density fields within a Gaussian statistic approximation. The second step makes a detailed analysis of the three-dimensional large-scale structures, assuming a fixed bias model and a fixed cosmology. This second step allows for the reconstruction of both the final density field and the initial conditions at z = 1000 assuming a fixed bias model. From these, we derive fields that self-consistently extrapolate the observed large-scale structures. We give two examples of these extrapolation and their utility for the detection of structures: the visibility of the Sloan Great Wall, and the detection and characterization of the Local Void using DIVA, a Lagrangian based technique to classify structures.

The relation between insulin-like growth factor I levels and cognition in healthy elderly: a meta-analysis.

PubMed

Arwert, L I; Deijen, J B; Drent, M L

2005-12-01

Insulin-like growth factor I (IGF-I) levels and cognitive functioning decrease with aging. Several studies report positive correlations between IGF-I levels and cognitive functioning in healthy elderly. However, because of controversial data no definitive conclusions can be drawn concerning the relation between IGF-I and cognition. Therefore, we carried out a meta-analysis on studies that report on the relation between IGF-I and cognition in healthy elderly. We searched the electronic databases for articles about IGF-I and cognition. Studies from 1985 to January 2005 are included. Two reviewers independently extracted data on study design and cognitive outcomes. Thirteen studies on IGF-I and cognition in elderly, with a total number of 1981 subjects, met the inclusion criteria. On the data from these studies meta-analyses were carried out by means of the program Comprehensive Meta-analysis using a random effects model. Pooled effects show that IGF-I levels in healthy elderly have a positive correlation with cognitive functioning, which appeared to be mainly measured with the mini mental state examination (MMSE). The effect size is 0.6, which indicates the presence of a large positive relationship between IGF and cognition in healthy elderly. These meta-analyses showed an overall relationship between IGF-I levels and cognitive functioning in healthy elderly. Further studies should be performed to clarify the role of IGF-I substitution in preserving cognitive functions with aging.

Testing moderation in network meta-analysis with individual participant data.

PubMed

Dagne, Getachew A; Brown, C Hendricks; Howe, George; Kellam, Sheppard G; Liu, Lei

2016-07-10

Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis.

PubMed

Anandan, C; Nurmatov, U; Sheikh, A

2009-06-01

There is conflicting evidence on the use of omega 3 and omega 6 supplementation for the prevention of allergic diseases. We conducted a systematic review evaluating the effectiveness of omega 3 and 6 oils for the primary prevention of sensitization and development of allergic disorders. We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double-blind randomized controlled trials. Two authors independently assessed articles for inclusion. Meta-analyses were undertaken using fixed effects modelling, or random effects modelling in the event of detecting significant heterogeneity. Of the 3129 articles identified, 10 reports (representing six unique studies) satisfied the inclusion criteria. Four studies compared omega 3 supplements with placebo and two studies compared omega 6 supplements with placebo. There was no clear evidence of benefit in relation to reduced risk of allergic sensitization or a favourable immunological profile. Meta-analyses failed to identify any consistent or clear benefits associated with use of omega 3 [atopic eczema: RR = 1.10 (95% CI 0.78-1.54); asthma: RR = 0.81 (95% CI 0.53-1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34-1.89) or food allergy RR = 0.51 (95% CI 0.10-2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56-1.16)] for the prevention of clinical disease. Contrary to the evidence from basic science and epidemiological studies, our systematic review and meta-analysis suggests that supplementation with omega 3 and omega 6 oils is probably unlikely to play an important role as a strategy for the primary prevention of sensitization or allergic disease.

[Comparison between one-step and two-step space closing methods of sliding mechanics using three-dimensional finite element].

PubMed

Han, Yaohui; Mou, Lan; Xu, Gengchi; Yang, Yiqiang; Ge, Zhenlin

2015-03-01

To construct a three-dimensional finite element model comparing between one-step and two-step methods in torque control of anterior teeth during space closure. Dicom image data including maxilla and upper teeth were obtained though cone-beam CT. A three-dimensional model was set up and the maxilla, upper teeth and periodontium were separated using Mimics software. The models were instantiated using Pro/Engineer software, and Abaqus finite element analysis software was used to simulate the sliding mechanics by loading 1.47 Nforce on traction hooks with different heights (2, 4, 6, 8, 10, 12 and 14 mm, respectively) in order to compare the initial displacement between six maxillary anterior teeth (one-step method) and four maxillary anterior teeth (two-step method). When moving anterior teeth bodily, initial displacements of central incisors in two-step method and in one-step method were 29.26 × 10⁻⁶ mm and 15.75 × 10⁻⁶ mm, respectively. The initial displacements of lateral incisors in two-step method and in one-step method were 46.76 × 10(-6) mm and 23.18 × 10(-6) mm, respectively. Under the same amount of light force, the initial displacement of anterior teeth in two-step method was doubled compared with that in one-step method. The root and crown of the canine couldn't obtain the same amount of displacement in one-step method. Two-step method could produce more initial displacement than one-step method. Therefore, two-step method was easier to achieve torque control of the anterior teeth during space closure.

Evidence-based mapping of design heterogeneity prior to meta-analysis: a systematic review and evidence synthesis.

PubMed

Althuis, Michelle D; Weed, Douglas L; Frankenfeld, Cara L

2014-07-23

Assessment of design heterogeneity conducted prior to meta-analysis is infrequently reported; it is often presented post hoc to explain statistical heterogeneity. However, design heterogeneity determines the mix of included studies and how they are analyzed in a meta-analysis, which in turn can importantly influence the results. The goal of this work is to introduce ways to improve the assessment and reporting of design heterogeneity prior to statistical summarization of epidemiologic studies. In this paper, we use an assessment of sugar-sweetened beverages (SSB) and type 2 diabetes (T2D) as an example to show how a technique called 'evidence mapping' can be used to organize studies and evaluate design heterogeneity prior to meta-analysis.. Employing a systematic and reproducible approach, we evaluated the following elements across 11 selected cohort studies: variation in definitions of SSB, T2D, and co-variables, design features and population characteristics associated with specific definitions of SSB, and diversity in modeling strategies. Evidence mapping strategies effectively organized complex data and clearly depicted design heterogeneity. For example, across 11 studies of SSB and T2D, 7 measured diet only once (with 7 to 16 years of disease follow-up), 5 included primarily low SSB consumers, and 3 defined the study variable (SSB) as consumption of either sugar or artificially-sweetened beverages. This exercise also identified diversity in analysis strategies, such as adjustment for 11 to 17 co-variables and a large degree of fluctuation in SSB-T2D risk estimates depending on variables selected for multivariable models (2 to 95% change in the risk estimate from the age-adjusted model). Meta-analysis seeks to understand heterogeneity in addition to computing a summary risk estimate. This strategy effectively documents design heterogeneity, thus improving the practice of meta-analysis by aiding in: 1) protocol and analysis planning, 2) transparent reporting of differences in study designs, and 3) interpretation of pooled estimates. We recommend expanding the practice of meta-analysis reporting to include a table that summarizes design heterogeneity. This would provide readers with more evidence to interpret the summary risk estimates.