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1.
    
Mediation hypothesis testing for a large number of mediators is challenging due to the composite structure of the null hypothesis, H 0 : α β = 0 ${H}_{0}:alpha beta =0$ ( α $alpha $ : effect of the exposure on the mediator after adjusting for confounders; β $beta $ : effect of the mediator on the outcome after adjusting for exposure and confounders). In this paper, we reviewed three classes of methods for large-scale one at a time mediation hypothesis testing. These methods are commonly used for continuous outcomes and continuous mediators assuming there is no exposure-mediator interaction so that the product α β $alpha beta $ has a causal interpretation as the indirect effect. The first class of methods ignores the impact of different structures under the composite null hypothesis, namely, (1) α = 0 , β ≠ 0 $alpha =0,beta ne 0$ ; (2) α ≠ 0 , β = 0 $alpha ne 0,beta =0$ ; and (3) α = β = 0 $alpha =beta =0$ . The second class of methods weights the reference distribution under each case of the null to form a mixture reference distribution. The third class constructs a composite test statistic using the three p values obtained under each case of the null so that the reference distribution of the composite statistic is approximately U ( 0 , 1 ) $U(0,1)$ . In addition to these existing methods, we developed the Sobel-comp method belonging to the second class, which uses a corrected mixture reference distribution for Sobel's test statistic. We performed extensive simulation studies to compare all six methods belonging to these three classes in terms of the false positive rates (FPRs) under the null hypothesis and the true positive rates under the alternative hypothesis. We found that the second class of methods which uses a mixture reference distribution could best maintain the FPRs at the nominal level under the null hypothesis and had the greatest true positive rates under the alternative hypothesis. We applied all methods to study the mediation mechanism of DNA methylation sites in the pathway from adult socioeconomic status to glycated hemoglobin level using data from the Multi-Ethnic Study of Atherosclerosis (MESA). We provide guidelines for choosing the optimal mediation hypothesis testing method in practice and develop an R package medScan available on the CRAN for implementing all the six methods.  相似文献   

2.
    
This article is motivated by a study of lung cancer prediction using breath volatile organic compound (VOC) biomarkers, where the challenge is that the predictors include not only high-dimensional time-dependent or functional VOC features but also the time-independent clinical variables. We consider a high-dimensional logistic regression and propose two different penalties: group spline-penalty or group smooth-penalty to handle the group structures of the time-dependent variables in the model. The new methods have the advantage for the situation where the model coefficients are sparse but change smoothly within the group, compared with other existing methods such as the group lasso and the group bridge approaches. Our methods are easy to implement since they can be turned into a group minimax concave penalty problem after certain transformations. We show that our fitting algorithm possesses the descent property and leads to attractive convergence properties. The simulation studies and the lung cancer application are performed to demonstrate the accuracy and stability of the proposed approaches.  相似文献   

3.
    
Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit‐normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two‐mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator‐outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

4.
    
Objective:Using a novel mediation method that presents unbiased results even in the presence of exposure–mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce.Methods:Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50–64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE).Results:Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37–1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15–1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27–1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health.Conclusions:Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.  相似文献   

5.
    
In genetic association studies, a single marker is often associated with multiple, correlated phenotypes (e.g., obesity and cardiovascular disease, or nicotine dependence and lung cancer). A pervasive question is then whether that marker exerts independent effects on all phenotypes. In this paper, we address this question by assessing whether there is a genetic effect on one phenotype that is not mediated through the other ones, so called direct genetic effect. Answering such question may represent an important step in the elucidation of the underlying biological mechanism. Under rather restrictive conditions, such direct genetic effects are known to be estimable by standard regression methods. Under more lenient conditions, in a prospective or unmatched case-control study, these effects can be estimated by using a previously proposed G-estimation method (Vansteelandt [2009] Epidemiology 20, 851-860). The present paper extends this method to matched case-control studies, and investigates the conditions under which this extension is valid. We illustrate the method on data from a matched case-control study, which we use to elucidate the pathway implications of a detected association between myocardial infarction and a genetic locus in the chromosomal region of the FTO gene.  相似文献   

6.
实施临床路径的意义和方法   总被引：184，自引：10，他引：184  
作者就临床路径的概念和内涵、由来和作用进行了描述；并介绍了临床路径的病种／病例选择和制定的方法、过程；阐述了改革对医院支付方式是实施临床路径的动力，转变医师的服务理念是推行临床路径的关键，各科室的协调与合作是实施临床路径的保证。  相似文献   

7.
目的 综合分析协商、调解、诉讼等医疗纠纷处理方式的使用情况,以期为完善医疗纠纷处理机制提供参考。方法 搜索近年研究医疗纠纷的相关文献,运用Meta分析方法对医疗纠纷案例研究中的数据进行统计和处理,分析各种医疗纠纷处理方式的使用分布情况。结果 在引入医疗纠纷人民调解之前,文献研究中各种处理方式所占比例分别为：双方协商解决65%、卫生行政调解23%、诉讼19%。而在引入医疗纠纷人民调解之后,文献研究中各种处理方式所占比例分别为双方协商解决75%、医疗纠纷人民调解17%、卫生行政调解1%、诉讼6%。结论 医患双方协商解决仍为目前医疗纠纷的主要处理方式,随着医疗纠纷人民调解的逐步发展,多元化的医疗纠纷处理机制将日趋完善。  相似文献   

8.
    
The goal of mediation analysis is to identify and explicate the mechanism that underlies a relationship between a risk factor and an outcome via an intermediate variable (mediator). In this paper, we consider the estimation of mediation effects in zero‐inflated (ZI) models intended to accommodate ‘extra’ zeros in count data. Focusing on the ZI negative binomial models, we provide a mediation formula approach to estimate the (overall) mediation effect in the standard two‐stage mediation framework under a key sequential ignorability assumption. We also consider a novel decomposition of the overall mediation effect for the ZI context using a three‐stage mediation model. Estimation of the components of the overall mediation effect requires an assumption involving the joint distribution of two counterfactuals. Simulation study results demonstrate low bias of mediation effect estimators and close‐to‐nominal coverage probability of confidence intervals. We also modify the mediation formula method by replacing ‘exact’ integration with a Monte Carlo integration method. The method is applied to a cohort study of dental caries in very low birth weight adolescents. For overall mediation effect estimation, sensitivity analysis was conducted to quantify the degree to which key assumption must be violated to reverse the original conclusion. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

9.
    
Randomized experiments are often complicated because of treatment noncompliance. This challenge prevents researchers from identifying the mediated portion of the intention‐to‐treated (ITT) effect, which is the effect of the assigned treatment that is attributed to a mediator. One solution suggests identifying the mediated ITT effect on the basis of the average causal mediation effect among compliers when there is a single mediator. However, considering the complex nature of the mediating mechanisms, it is natural to assume that there are multiple variables that mediate through the causal path. Motivated by an empirical analysis of a data set collected in a randomized interventional study, we develop a method to estimate the mediated portion of the ITT effect when both multiple dependent mediators and treatment noncompliance exist. This enables researchers to make an informed decision on how to strengthen the intervention effect by identifying relevant mediators despite treatment noncompliance. We propose a nonparametric estimation procedure and provide a sensitivity analysis for key assumptions. We conduct a Monte Carlo simulation study to assess the finite sample performance of the proposed approach. The proposed method is illustrated by an empirical analysis of JOBS II data, in which a job training intervention was used to prevent mental health deterioration among unemployed individuals.  相似文献   

10.
论2种调解方式结合处理医疗纠纷的新机制   总被引：3，自引：1，他引：3  
医疗纠纷近年成为社会热点之一,目前医疗纠纷的调解主要采取人民调解与行政调解2种方式,通过分析两者的特点,人民调解更具有优势。  相似文献   

11.
This study investigated the mediating mechanisms responsible for the effects of a program designed to reduce intentions to use anabolic steroids, improve nutrition, and increase strength training self-efficacy. Fifteen of 31 high school football teams (N = 1,506 players at baseline) in Oregon and Washington were assigned to receive the intervention. The multicomponent program addressed the social influences promoting ergogenic drug use and engaging students in healthy nutrition and strength training alternative behaviors. Although the results differed across the three dependent variables, the program appeared to work by changing team norms. Unlike prevention of other drugs, changes in knowledge and perceived severity were mediators of program effects in this study.  相似文献   

12.
    
Next generation sequencing technologies have made it possible to investigate the role of rare variants (RVs) in disease etiology. Because RVs associated with disease susceptibility tend to be enriched in families with affected individuals, study designs based on affected sib pairs (ASP) can be more powerful than case–control studies. We construct tests of RV-set association in ASPs for single genomic regions as well as for multiple regions. Single-region tests can efficiently detect a gene region harboring susceptibility variants, while multiple-region extensions are meant to capture signals dispersed across a biological pathway, potentially as a result of locus heterogeneity. Within ascertained ASPs, the test statistics contrast the frequencies of duplicate rare alleles (usually appearing on a shared haplotype) against frequencies of a single rare allele copy (appearing on a nonshared haplotype); we call these allelic parity tests. Incorporation of minor allele frequency estimates from reference populations can markedly improve test efficiency. Under various genetic penetrance models, application of the tests in simulated ASP data sets demonstrates good type I error properties as well as power gains over approaches that regress ASP rare allele counts on sharing state, especially in small samples. We discuss robustness of the allelic parity methods to the presence of genetic linkage, misspecification of reference population allele frequencies, sequencing error and de novo mutations, and population stratification. As proof of principle, we apply single- and multiple-region tests in a motivating study data set consisting of whole exome sequencing of sisters ascertained with early onset breast cancer.  相似文献   

13.
    
Tom Ten Have made many contributions to causal inference and biostatistics before his untimely death. This paper reviews Tom's contributions and discusses potential related future research directions. We focus on Tom's contributions to longitudinal/repeated measures categorical data analysis and particularly his contributions to causal inference. Tom's work on causal inference was primarily in the areas of estimating the effect of receiving treatment in randomized trials with nonadherence and mediation analysis. A related area to mediation analysis he was working on at the time of his death was posttreatment effect modification with applications to designing adaptive treatment strategies. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

14.
    
Objectives:Shift work may be associated with an increased incidence of respiratory infections. However, underlying mechanisms are unclear. Therefore, our aim was to examine the mediating role of sleep, physical activity, and diet in the association between shift work and respiratory infections.Methods:This prospective cohort study included 396 shift and non-shift workers employed in hospitals. At baseline, sleep duration and physical activity were measured using actigraphy and sleep/activity diaries, sleep quality was reported, and frequency of meal and snack consumption was measured using food diaries. In the following six months, participants used a smartphone application to report their influenza-like illness/acute respiratory infection (ILI/ARI) symptoms daily. Mediation analysis of sleep, physical activity, and diet as potential mediators of the effect of shift work on ILI/ARI incidence rate was performed using structural equation modeling with negative binomial and logistic regression.Results:Shift workers had a 23% [incidence rate ratio (IRR) 1.23, 95% CI 1.01–1.49] higher incidence rate of ILI/ARI than non-shift workers. After adding the potential mediators to the model, this reduced to 15% (IRR 1.15, 95% CI 0.94–1.40). The largest mediating (ie, indirect) effect was found for poor sleep quality, with shift workers having 29% more ILI/ARI episodes via the pathway of poorer sleep quality (IRR 1.29, 95% CI 1.02–1.95).Conclusions:Compared to non-shift workers, shift workers had a higher incidence rate of ILI/ARI that was partly mediated by poorer sleep quality. Therefore, it may be relevant for future research to focus on perceived sleep quality as an underlying mechanism in the relation between shift work and increased infection susceptibility.  相似文献   

15.
The purpose of this investigation was to determine if the Aban Aya Youth Project, a culturally grounded intervention, produced differences in changes over time in core intervening variables (i.e., communal value orientation, empathy, violence avoidance efficacy beliefs) and whether these variables mediated intervention effects on the development of youth violent behavior. Fifth grade cohorts at 12 schools were randomly assigned to one of two intervention conditions or an attention placebo control condition and followed longitudinally through eighth grade. A total of 668 students (49% male) participated in the study. Mediation analyses suggested that both program conditions (as compared to the control condition) led to steeper increases over time in empathy which, in turn were related to reductions in the likelihood of violent behavior over time. No other significant program effects were detected, although changes over time in violence avoidance efficacy were associated with reduced likelihood of violent behavior. Findings are discussed in terms of theory development, program development and points of refinement of the Aban Aya Youth Project and implications for future research.  相似文献   

16.
    
Chronic diseases develop via complex pathways, depending on the degree of exposure to risk factors from early in life and childhood onward. Metabolic syndrome has multiple risk factors, including genetic factors, inappropriate diet, and insufficient physical activity. This study classified health-related behavior classes in childhood and adolescents and analyzed the direct and indirect effects of each class on the metabolic risk in inflammation-mediated pathways. We identified the health-related lifestyle classes based on health-related behavior indicators in subjects aged 3–15 years who participated in the Ewha Birth and Growth Cohort Study by using a latent class analysis. A mediation analysis was performed to access the direct and indirect effects of each class on the continuous metabolic syndrome score (cMetS), with the inflammatory index used as a mediating factor. Subjects were classified into inactive and positive lifestyle classes according to their characteristics. In the inactive lifestyle class, interleukin (IL)-6 and cMetS had a significant association. The study confirmed that IL-6 exerts a significant indirect effect between inactive lifestyle and cMetS. This result supports previous studies. Since the health behaviors of children and adolescents can affect the likelihood of subsequent metabolic syndrome, appropriate health behavior interventions for this period are needed.  相似文献   

17.
In the present study a German-speaking scale for measuring parental mediation of television is tested and various factors influencing television mediation are investigated. 252 German-speaking Swiss parents of children aged 3 to 14 answered questions about their mediation behavior and possible determinants. The results confirm international research findings. Active and restrictive mediation as well as coviewing are identified as important mediation styles in German-speaking Switzerland. Though in detail the mediation styles show different determinant patterns, altogether parental attitudes toward television, family interaction patterns, and children's age prove to be central determinants of television mediation styles. Sociodemographic and structural factors seem to become less important.  相似文献   

18.

Objective

This study investigated variables that may mediate the relationship between advertising susceptibility and adolescent preference for and consumption of sugar-sweetened beverages (SSBs), with the goal of informing inoculation-based mitigation approaches grounded in media literacy and messaging resistance.

Design

The study utilized data from a nationally representative sample of US adolescents (ages 12–17 years, n?=?1,657) from the National Cancer Institute's Family Life, Activity, Sun, Health, and Eating survey.

Main Outcome Measure

Variables of interest were SSB preference and consumption, advertising susceptibility, perceived self-efficacy to make good nutritional choices, perceived SSB consumption by peers, and attitude toward SSBs. Exposure to obesogenic environments was examined as a moderator.

Analysis

Direct and mediated associations between advertising susceptibility and SSB preference were estimated through a series of regression and mediation analyses.

Results

Advertising susceptibility was a strong predictor of SSB preference (unstandardized B?=?.29, SE?=?.026, P < .001), which, in turn, was a strong predictor of consumption (unstandardized B?=?.10, SE?=?.01, P < .001), controlling for potential mediators. The only statistically significant mediator of this association was perceived peer consumption (unstandardized B?=?.38, SE?=?.08, P < .001), which was stronger for adolescents with higher exposure to obesogenic environments.

Conclusions and Implications

This study offers developers of inoculation-based strategies additional insight into levers that could be targeted for building adolescent resistance to advertising effects.  相似文献   

19.
    
Glioblastoma multiforme (GBM), the most common type of malignant brain tumor, is highly fatal. Limited understanding of its rapid progression necessitates additional approaches that integrate what is known about the genomics of this cancer. Using a discovery set (n = 348) and a validation set (n = 174) of GBM patients, we performed genome‐wide analyses that integrated mRNA and micro‐RNA expression data from GBM as well as associated survival information, assessing coordinated variability in each as this reflects their known mechanistic functions. Cox proportional hazards models were used for the survival analyses, and nonparametric permutation tests were performed for the micro‐RNAs to investigate the association between the number of associated genes and its prognostication. We also utilized mediation analyses for micro‐RNA‐gene pairs to identify their mediation effects. Genome‐wide analyses revealed a novel pattern: micro‐RNAs related to more gene expressions are more likely to be associated with GBM survival (P = 4.8 × 10?5). Genome‐wide mediation analyses for the 32,660 micro‐RNA‐gene pairs with strong association (false discovery rate [FDR] < 0.01%) identified 51 validated pairs with significant mediation effect. Of the 51 pairs, miR‐223 had 16 mediation genes. These 16 mediation genes of miR‐223 were also highly associated with various other micro‐RNAs and mediated their prognostic effects as well. We further constructed a gene signature using the 16 genes, which was highly associated with GBM survival in both the discovery and validation sets (P = 9.8 × 10?6). This comprehensive study discovered mediation effects of micro‐RNA to gene expression and GBM survival and provided a new analytic framework for integrative genomics.  相似文献   

20.
    
BACKGROUND: Frailty is associated with adverse health outcomes, and vitamin D (VD) deficiency may be a risk factor. We aimed to identify frailty trajectories and examine the mediating effect of physical activity (PA) on the association between VD deficiency and frailty trajectories. METHODS: We included 2997 participants aged 60 to 85 years from ELSA. VD was measured using serum 25-hydroxyvitamin D [25(OH)D] (sufficient: >50; insufficient: 30–50; deficient: <30 nmol/L). Frailty was assessed by a 60-item frailty index, and PA was measured on the basis of total energy expenditure. Frailty trajectories were identified using group-based trajectory modeling, and the mediation effect of PA was tested using causal mediation analysis. RESULTS: Three distinct frailty trajectories emerged: “Non-frail” (66.48%), “Pre-frail to frail” (25.67%) and “Frail to severely frail” (7.85%). VD deficiency was associated with the “Pre-frail to frail” (OR = 1.51, 95% CI: 1.14, 1.98) and “Frail to severely frail” trajectories (OR = 2.29, 95% CI: 1.45, 3.62). PA only mediated 48.4% (95% CI: 17.1%–270.8%) of the association between VD deficiency and the “Pre-frail to frail” trajectory. CONCLUSIONS: Vitamin D deficiency is associated with the onset and worsening of frailty in older adults, and reduced PA may mediate its impact on the transition from pre-frailty to frailty.  相似文献   

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