Identification of confounders in the assessment of the relationship between lead exposure and child development.

PubMed

Tong, I S; Lu, Y

2001-01-01

To explore the best approach to identify and adjust for confounders in epidemiologic practice. In the Port Pirie cohort study, the selection of covariates was based on both a priori and an empirical consideration. In an assessment of the relationship between exposure to environmental lead and child development, change-in-estimate (CE) and significance testing (ST) criteria were compared in identifying potential confounders. The Pearson correlation coefficients were used to evaluate the potential for collinearity between pairs of major quantitative covariates. In multivariate analyses, the effects of confounding factors were assessed with multiple linear regression models. The nature and number of covariates selected varied with different confounder selection criteria and different cutoffs. Four covariates (i.e., quality of home environment, socioeconomic status (SES), maternal intelligence, and parental smoking behaviour) met the conventional CE criterion (> or =10%), whereas 14 variables met the ST criterion (p < or = 0.25). However, the magnitude of the relationship between blood lead concentration and children's IQ differed slightly after adjustment for confounding, using either the CE (partial regression coefficient: -4.4; 95% confidence interval (CI): -0.5 to -8.3) or ST criterion (-4.3; 95% CI: -0.2 to -8.4). Identification and selection of confounding factors need to be viewed cautiously in epidemiologic studies. Either the CE (e.g., > or = 10%) or ST (e.g., p < or = 0.25) criterion may be implemented in identification of a potential confounder if a study sample is sufficiently large, and both the methods are subject to arbitrariness of selecting a cut-off point. In this study, the CE criterion (i.e., > or = 10%) appears to be more stringent than the ST method (i.e., p < or = 0.25) in the identification of confounders. However, the ST rule cannot be used to determine the trueness of confounding because it cannot reflect the causal relationship between the confounder and outcome. This study shows the complexities one can expect to encounter in the identification of and adjustment for confounders.

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

"A Bayesian sensitivity analysis to evaluate the impact of unmeasured confounding with external data: a real world comparative effectiveness study in osteoporosis".

PubMed

Zhang, Xiang; Faries, Douglas E; Boytsov, Natalie; Stamey, James D; Seaman, John W

2016-09-01

Observational studies are frequently used to assess the effectiveness of medical interventions in routine clinical practice. However, the use of observational data for comparative effectiveness is challenged by selection bias and the potential of unmeasured confounding. This is especially problematic for analyses using a health care administrative database, in which key clinical measures are often not available. This paper provides an approach to conducting a sensitivity analyses to investigate the impact of unmeasured confounding in observational studies. In a real world osteoporosis comparative effectiveness study, the bone mineral density (BMD) score, an important predictor of fracture risk and a factor in the selection of osteoporosis treatments, is unavailable in the data base and lack of baseline BMD could potentially lead to significant selection bias. We implemented Bayesian twin-regression models, which simultaneously model both the observed outcome and the unobserved unmeasured confounder, using information from external sources. A sensitivity analysis was also conducted to assess the robustness of our conclusions to changes in such external data. The use of Bayesian modeling in this study suggests that the lack of baseline BMD did have a strong impact on the analysis, reversing the direction of the estimated effect (odds ratio of fracture incidence at 24 months: 0.40 vs. 1.36, with/without adjusting for unmeasured baseline BMD). The Bayesian twin-regression models provide a flexible sensitivity analysis tool to quantitatively assess the impact of unmeasured confounding in observational studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nonlinear Predictive Models for Multiple Mediation Analysis: With an Application to Explore Ethnic Disparities in Anxiety and Depression Among Cancer Survivors.

PubMed

Yu, Qingzhao; Medeiros, Kaelen L; Wu, Xiaocheng; Jensen, Roxanne E

2018-04-02

Mediation analysis allows the examination of effects of a third variable (mediator/confounder) in the causal pathway between an exposure and an outcome. The general multiple mediation analysis method (MMA), proposed by Yu et al., improves traditional methods (e.g., estimation of natural and controlled direct effects) to enable consideration of multiple mediators/confounders simultaneously and the use of linear and nonlinear predictive models for estimating mediation/confounding effects. Previous studies find that compared with non-Hispanic cancer survivors, Hispanic survivors are more likely to endure anxiety and depression after cancer diagnoses. In this paper, we applied MMA on MY-Health study to identify mediators/confounders and quantify the indirect effect of each identified mediator/confounder in explaining ethnic disparities in anxiety and depression among cancer survivors who enrolled in the study. We considered a number of socio-demographic variables, tumor characteristics, and treatment factors as potential mediators/confounders and found that most of the ethnic differences in anxiety or depression between Hispanic and non-Hispanic white cancer survivors were explained by younger diagnosis age, lower education level, lower proportions of employment, less likely of being born in the USA, less insurance, and less social support among Hispanic patients.

Interpretational confounding is due to misspecification, not to type of indicator: comment on Howell, Breivik, and Wilcox (2007).

PubMed

Bollen, Kenneth A

2007-06-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. Copyright 2007 APA, all rights reserved.

Addressing unmeasured confounding in comparative observational research.

PubMed

Zhang, Xiang; Faries, Douglas E; Li, Hu; Stamey, James D; Imbens, Guido W

2018-04-01

Observational pharmacoepidemiological studies can provide valuable information on the effectiveness or safety of interventions in the real world, but one major challenge is the existence of unmeasured confounder(s). While many analytical methods have been developed for dealing with this challenge, they appear under-utilized, perhaps due to the complexity and varied requirements for implementation. Thus, there is an unmet need to improve understanding the appropriate course of action to address unmeasured confounding under a variety of research scenarios. We implemented a stepwise search strategy to find articles discussing the assessment of unmeasured confounding in electronic literature databases. Identified publications were reviewed and characterized by the applicable research settings and information requirements required for implementing each method. We further used this information to develop a best practice recommendation to help guide the selection of appropriate analytical methods for assessing the potential impact of unmeasured confounding. Over 100 papers were reviewed, and 15 methods were identified. We used a flowchart to illustrate the best practice recommendation which was driven by 2 critical components: (1) availability of information on the unmeasured confounders; and (2) goals of the unmeasured confounding assessment. Key factors for implementation of each method were summarized in a checklist to provide further assistance to researchers for implementing these methods. When assessing comparative effectiveness or safety in observational research, the impact of unmeasured confounding should not be ignored. Instead, we suggest quantitatively evaluating the impact of unmeasured confounding and provided a best practice recommendation for selecting appropriate analytical methods. Copyright © 2018 John Wiley & Sons, Ltd.

Adjusting for geographic variation in observational comparative effectiveness studies: a case study of antipsychotics using state Medicaid data.

PubMed

Root, Elisabeth Dowling; Thomas, Deborah S K; Campagna, Elizabeth J; Morrato, Elaine H

2014-08-27

Area-level variation in treatment and outcomes may be a potential source of confounding bias in observational comparative effectiveness studies. This paper demonstrates how to use exploratory spatial data analysis (ESDA) and spatial statistical methods to investigate and control for these potential biases. The case presented compares the effectiveness of two antipsychotic treatment strategies: oral second-generation antipsychotics (SGAs) vs. long-acting paliperiodone palmitate (PP). A new-start cohort study was conducted analyzing patient-level administrative claims data (8/1/2008-4/30/2011) from Missouri Medicaid. ESDA techniques were used to examine spatial patterns of antipsychotic prescriptions and outcomes (hospitalization and emergency department (ED) visits). Likelihood of mental health-related outcomes were compared between patients starting PP (N = 295) and oral SGAs (N = 8,626) using multilevel logistic regression models adjusting for patient composition (demographic and clinical factors) and geographic region. ESDA indicated significant spatial variation in antipsychotic prescription patterns and moderate variation in hospitalization and ED visits thereby indicating possible confounding by geography. In the multilevel models for this antipsychotic case example, patient composition represented a stronger source of confounding than geographic context. Because geographic variation in health care delivery is ubiquitous, it could be a comparative effectiveness research (CER) best practice to test for possible geographic confounding in observational data. Though the magnitude of the area-level geography effects were small in this case, they were still statistically significant and should therefore be examined as part of this observational CER study. More research is needed to better estimate the range of confounding due to geography across different types of observational comparative effectiveness studies and healthcare utilization outcomes.

Doubly robust matching estimators for high dimensional confounding adjustment.

PubMed

Antonelli, Joseph; Cefalu, Matthew; Palmer, Nathan; Agniel, Denis

2018-05-11

Valid estimation of treatment effects from observational data requires proper control of confounding. If the number of covariates is large relative to the number of observations, then controlling for all available covariates is infeasible. In cases where a sparsity condition holds, variable selection or penalization can reduce the dimension of the covariate space in a manner that allows for valid estimation of treatment effects. In this article, we propose matching on both the estimated propensity score and the estimated prognostic scores when the number of covariates is large relative to the number of observations. We derive asymptotic results for the matching estimator and show that it is doubly robust in the sense that only one of the two score models need be correct to obtain a consistent estimator. We show via simulation its effectiveness in controlling for confounding and highlight its potential to address nonlinear confounding. Finally, we apply the proposed procedure to analyze the effect of gender on prescription opioid use using insurance claims data. © 2018, The International Biometric Society.

Does consideration of larger study areas yield more accurate estimates of air pollution health effects? An illustration of the bias-variance trade-off in air pollution epidemiology.

PubMed

Pedersen, Marie; Siroux, Valérie; Pin, Isabelle; Charles, Marie Aline; Forhan, Anne; Hulin, Agnés; Galineau, Julien; Lepeule, Johanna; Giorgis-Allemand, Lise; Sunyer, Jordi; Annesi-Maesano, Isabella; Slama, Rémy

2013-10-01

Spatially-resolved air pollution models can be developed in large areas. The resulting increased exposure contrasts and population size offer opportunities to better characterize the effect of atmospheric pollutants on respiratory health. However the heterogeneity of these areas may also enhance the potential for confounding. We aimed to discuss some analytical approaches to handle this trade-off. We modeled NO2 and PM10 concentrations at the home addresses of 1082 pregnant mothers from EDEN cohort living in and around urban areas, using ADMS dispersion model. Simulations were performed to identify the best strategy to limit confounding by unmeasured factors varying with area type. We examined the relation between modeled concentrations and respiratory health in infants using regression models with and without adjustment or interaction terms with area type. Simulations indicated that adjustment for area limited the bias due to unmeasured confounders varying with area at the costs of a slight decrease in statistical power. In our cohort, rural and urban areas differed for air pollution levels and for many factors associated with respiratory health and exposure. Area tended to modify effect measures of air pollution on respiratory health. Increasing the size of the study area also increases the potential for residual confounding. Our simulations suggest that adjusting for type of area is a good option to limit residual confounding due to area-associated factors without restricting the area size. Other statistical approaches developed in the field of spatial epidemiology are an alternative to control for poorly-measured spatially-varying confounders. © 2013 Elsevier Ltd. All rights reserved.

Which Propensity Score Method Best Reduces Confounder Imbalance? An Example From a Retrospective Evaluation of a Childhood Obesity Intervention.

PubMed

Schroeder, Krista; Jia, Haomiao; Smaldone, Arlene

Propensity score (PS) methods are increasingly being employed by researchers to reduce bias arising from confounder imbalance when using observational data to examine intervention effects. The purpose of this study was to examine PS theory and methodology and compare application of three PS methods (matching, stratification, weighting) to determine which best improves confounder balance. Baseline characteristics of a sample of 20,518 school-aged children with severe obesity (of whom 1,054 received an obesity intervention) were assessed prior to PS application. Three PS methods were then applied to the data to determine which showed the greatest improvement in confounder balance between the intervention and control group. The effect of each PS method on the outcome variable-body mass index percentile change at one year-was also examined. SAS 9.4 and Comprehensive Meta-analysis statistical software were used for analyses. Prior to PS adjustment, the intervention and control groups differed significantly on seven of 11 potential confounders. PS matching removed all differences. PS stratification and weighting both removed one difference but created two new differences. Sensitivity analyses did not change these results. Body mass index percentile at 1 year decreased in both groups. The size of the decrease was smaller in the intervention group, and the estimate of the decrease varied by PS method. Selection of a PS method should be guided by insight from statistical theory and simulation experiments, in addition to observed improvement in confounder balance. For this data set, PS matching worked best to correct confounder imbalance. Because each method varied in correcting confounder imbalance, we recommend that multiple PS methods be compared for ability to improve confounder balance before implementation in evaluating treatment effects in observational data.

Restricted spatial regression in practice: Geostatistical models, confounding, and robustness under model misspecification

USGS Publications Warehouse

Hanks, Ephraim M.; Schliep, Erin M.; Hooten, Mevin B.; Hoeting, Jennifer A.

2015-01-01

In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa.

Adaptive design of visual perception experiments

NASA Astrophysics Data System (ADS)

O'Connor, John D.; Hixson, Jonathan; Thomas, James M., Jr.; Peterson, Matthew S.; Parasuraman, Raja

2010-04-01

Meticulous experimental design may not always prevent confounds from affecting experimental data acquired during visual perception experiments. Although experimental controls reduce the potential effects of foreseen sources of interference, interaction, or noise, they are not always adequate for preventing the confounding effects of unforeseen forces. Visual perception experimentation is vulnerable to unforeseen confounds because of the nature of the associated cognitive processes involved in the decision task. Some confounds are beyond the control of experimentation, such as what a participant does immediately prior to experimental participation, or the participant's attitude or emotional state. Other confounds may occur through ignorance of practical control methods on the part of the experiment's designer. The authors conducted experiments related to experimental fatigue and initially achieved significant results that were, upon re-examination, attributable to a lack of adequate controls. Re-examination of the original results and the processes and events that led to them yielded a second experimental design with more experimental controls and significantly different results. The authors propose that designers of visual perception experiments can benefit from planning to use a test-fix-test or adaptive experimental design cycle, so that unforeseen confounds in the initial design can be remedied.

A comparison of propensity score-based approaches to health service evaluation: a case study of a preoperative physician-led clinic for high-risk surgical patients.

PubMed

Pham, Clarabelle T; Gibb, Catherine L; Mittinty, Murthy N; Fitridge, Robert A; Marshall, Villis R; Karnon, Jonathan D

2016-10-01

A physician-led clinic for the preoperative optimization and management of high-risk surgical patients was implemented in a South Australian public hospital in 2008. This study aimed to estimate the costs and effects of the clinic using a mixed retrospective and prospective observational study design. Alternative propensity score estimation methods were applied to retrospective routinely collected administrative and clinical data, using weighted and matched cohorts. Supplementary survey-based prospective data were collected to inform the analysis of the retrospective data and reduce potential unmeasured confounding. Using weighted cohorts, clinic patients had a significantly longer mean length of stay and higher mean cost. With the matched cohorts, reducing the calliper width resulted in a shorter mean length of stay in the clinic group, but the costs remained significantly higher. The prospective data indicated potential unmeasured confounding in all analyses other than in the most tightly matched cohorts. The application of alternative propensity-based approaches to a large sample of retrospective data, supplemented with a smaller sample of prospective data, informed a pragmatic approach to reducing potential observed and unmeasured confounding in an evaluation of a physician-led preoperative clinic. The need to generate tightly matched cohorts to reduce the potential for unmeasured confounding indicates that significant uncertainty remains around the effects of the clinic. This study illustrates the value of mixed retrospective and prospective observational study designs but also underlines the need to prospectively plan for the evaluation of costs and effects alongside the implementation of significant service innovations. © 2016 John Wiley & Sons, Ltd.

The relationship between urinary tract infection during pregnancy and preeclampsia: causal, confounded or spurious?

PubMed

Karmon, Anatte; Sheiner, Eyal

2008-06-01

Preeclampsia is a major cause of maternal morbidity, although its precise etiology remains elusive. A number of studies suggest that urinary tract infection (UTI) during the course of gestation is associated with elevated risk for preeclampsia, while others have failed to prove such an association. In our medical center, pregnant women who were exposed to at least one UTI episode during pregnancy were 1.3 times more likely to have mild preeclampsia and 1.8 times more likely to have severe preeclampsia as compared to unexposed women. Our results are based on univariate analyses and are not adjusted for potential confounders. This editorial aims to discuss the relationship between urinary tract infection and preeclampsia, as well as examine the current problems regarding the interpretation of this association. Although the relationship between UTI and preeclampsia has been demonstrated in studies with various designs, carried-out in a variety of settings, the nature of this association is unclear. By taking into account timeline, dose-response effects, treatment influences, and potential confounders, as well as by neutralizing potential biases, future studies may be able to clarify the relationship between UTI and preeclampsia by determining if it is causal, confounded, or spurious.

How Confounder Strength Can Affect Allocation of Resources in Electronic Health Records.

PubMed

Lynch, Kristine E; Whitcomb, Brian W; DuVall, Scott L

2018-01-01

When electronic health record (EHR) data are used, multiple approaches may be available for measuring the same variable, introducing potentially confounding factors. While additional information may be gleaned and residual confounding reduced through resource-intensive assessment methods such as natural language processing (NLP), whether the added benefits offset the added cost of the additional resources is not straightforward. We evaluated the implications of misclassification of a confounder when using EHRs. Using a combination of simulations and real data surrounding hospital readmission, we considered smoking as a potential confounder. We compared ICD-9 diagnostic code assignment, which is an easily available measure but has the possibility of substantial misclassification of smoking status, with NLP, a method of determining smoking status that more expensive and time-consuming than ICD-9 code assignment but has less potential for misclassification. Classification of smoking status with NLP consistently produced less residual confounding than the use of ICD-9 codes; however, when minimal confounding was present, differences between the approaches were small. When considerable confounding is present, investing in a superior measurement tool becomes advantageous.

Gene × environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution.

PubMed

Keller, Matthew C

2014-01-01

Candidate gene × environment (G × E) interaction research tests the hypothesis that the effects of some environmental variable (e.g., childhood maltreatment) on some outcome measure (e.g., depression) depend on a particular genetic polymorphism. Because this research is inherently nonexperimental, investigators have been rightly concerned that detected interactions could be driven by confounders (e.g., ethnicity, gender, age, socioeconomic status) rather than by the specified genetic or environmental variables per se. In an attempt to eliminate such alternative explanations for detected G × E interactions, investigators routinely enter the potential confounders as covariates in general linear models. However, this practice does not control for the effects these variables might have on the G × E interaction. Rather, to properly control for confounders, researchers need to enter the covariate × environment and the covariate × gene interaction terms in the same model that tests the G × E term. In this manuscript, I demonstrate this point analytically and show that the practice of improperly controlling for covariates is the norm in the G × E interaction literature to date. Thus, many alternative explanations for G × E findings that investigators had thought were eliminated have not been. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

PubMed

Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

2017-08-24

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Instrumental variable methods in comparative safety and effectiveness research.

PubMed

Brookhart, M Alan; Rassen, Jeremy A; Schneeweiss, Sebastian

2010-06-01

Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial.

Directed acyclic graphs (DAGs): an aid to assess confounding in dental research.

PubMed

Merchant, Anwar T; Pitiphat, Waranuch

2002-12-01

Confounding, a special type of bias, occurs when an extraneous factor is associated with the exposure and independently affects the outcome. In order to get an unbiased estimate of the exposure-outcome relationship, we need to identify potential confounders, collect information on them, design appropriate studies, and adjust for confounding in data analysis. However, it is not always clear which variables to collect information on and adjust for in the analyses. Inappropriate adjustment for confounding can even introduce bias where none existed. Directed acyclic graphs (DAGs) provide a method to select potential confounders and minimize bias in the design and analysis of epidemiological studies. DAGs have been used extensively in expert systems and robotics. Robins (1987) introduced the application of DAGs in epidemiology to overcome shortcomings of traditional methods to control for confounding, especially as they related to unmeasured confounding. DAGs provide a quick and visual way to assess confounding without making parametric assumptions. We introduce DAGs, starting with definitions and rules for basic manipulation, stressing more on applications than theory. We then demonstrate their application in the control of confounding through examples of observational and cross-sectional epidemiological studies.

Childhood Medical and Behavioral Consequences of Maternal Cocaine Use1

PubMed Central

Singer, Lynn; Farkas, Kathleen; Kliegman, Robert

2014-01-01

Reviewed available studies of the impact of fetal cocaine exposure on child medical and developmental outcome, as well as the current status of clinical psychological interventions and research strategies. Current studies are inconclusive but suggest that prenatal exposure to crack-cocaine can have significant effects on the growth and neurological development of the infant, with the potential of later learning and behavioral disabilities. Social-environmental correlates of maternal cocaine use are confounding factors with known negative effects on child outcome. Large, population-based studies using multivariate analyses are needed to determine the independent effects of cocaine on child outcome relative to other confounding variables. PMID:1382125

Factors Influencing Observed Tillage Impacts on Herbicide Transport

USDA-ARS?s Scientific Manuscript database

The widespread use and potential human health effects of the herbicides atrazine and glyphosate have generated interest in establishing how no-tillage impacts loading of these herbicides to runoff water in comparison to other tillage practices. In this study, potentially confounding factors such as ...

Cryptic confounding compounds: A brief consideration of the influences of anthropogenic contaminants on courtship and mating behavior

PubMed Central

Blocker, Tomica D.; Ophir, Alexander G.

2012-01-01

Contaminants, like pesticides, polychlorinated biphenyls (PCBs), dioxins and metals, are persistent and ubiquitous and are known to threaten the environment. Traditionally, scientists have considered the direct physiological risks that these contaminants pose. However, scientists have just begun to integrate ethology and toxicology to investigate the effects that contaminants have on behavior. This review considers the potential for contaminant effects on mating behavior. Here we assess the growing body of research concerning disruptions in sexual differentiation, courtship, sexual receptivity, arousal, and mating. We discuss the implications of these disruptions on conservation efforts and highlight the importance of recognizing the potential for environmental stressors to affect behavioral experimentation. More specifically, we consider the negative implications for anthropogenic contaminants to affect the immediate behavior of animals, and their potential to have cascading and/or long-term effects on the behavioral ecology and evolution of populations. Overall, we aim to raise awareness of the confounding influence that contaminants can have, and promote caution when interpreting results where the potential for cryptic affects are possible. PMID:24244068

Effects of categorization method, regression type, and variable distribution on the inflation of Type-I error rate when categorizing a confounding variable.

PubMed

Barnwell-Ménard, Jean-Louis; Li, Qing; Cohen, Alan A

2015-03-15

The loss of signal associated with categorizing a continuous variable is well known, and previous studies have demonstrated that this can lead to an inflation of Type-I error when the categorized variable is a confounder in a regression analysis estimating the effect of an exposure on an outcome. However, it is not known how the Type-I error may vary under different circumstances, including logistic versus linear regression, different distributions of the confounder, and different categorization methods. Here, we analytically quantified the effect of categorization and then performed a series of 9600 Monte Carlo simulations to estimate the Type-I error inflation associated with categorization of a confounder under different regression scenarios. We show that Type-I error is unacceptably high (>10% in most scenarios and often 100%). The only exception was when the variable categorized was a continuous mixture proxy for a genuinely dichotomous latent variable, where both the continuous proxy and the categorized variable are error-ridden proxies for the dichotomous latent variable. As expected, error inflation was also higher with larger sample size, fewer categories, and stronger associations between the confounder and the exposure or outcome. We provide online tools that can help researchers estimate the potential error inflation and understand how serious a problem this is. Copyright © 2014 John Wiley & Sons, Ltd.

The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

PubMed Central

Smith, Eric G.

2015-01-01

Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is straightforward.  The method's routine usefulness, however, has not yet been established, nor has the method been fully validated. Rapid further investigation of this novel method is clearly indicated, given the potential value of its quantitative or qualitative output. PMID:25580226

A systematic literature review on the efficacy–effectiveness gap: comparison of randomized controlled trials and observational studies of glucose-lowering drugs

PubMed Central

Ankarfeldt, Mikkel Z; Adalsteinsson, Erpur; Groenwold, Rolf HH; Ali, M Sanni; Klungel, Olaf H

2017-01-01

Aim To identify a potential efficacy–effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. Methods A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome. Medline, Embase, Current Content, and Biosis were searched. Information on effect estimates, baseline characteristics of the study population, publication year, study duration, and number of patients, and for observational studies, characteristics related to confounding adjustment and selection- and information bias were extracted. Results From 312 hits, 11 RCTs and 7 observational studies comparing GLP-1 with insulin, and from 474 hits, 16 RCTs and 4 observational studies comparing DPP-4i with sulfonylurea were finally included. No differences were observed in baseline characteristics of the study populations (age, sex, body mass index, time since diagnosis of type 2 diabetes mellitus, and HbA1c) or effect sizes across study designs. Mean effect sizes ranged from −0.43 to 0.91 and from −0.80 to 1.13 in RCTs and observational studies, respectively, comparing GLP-1 with insulin, and from −0.13 to 2.70 and −0.20 to 0.30 in RCTs and observational studies, respectively, comparing DPP-4i and sulfonylurea. Generally, the identified observational studies held potential flaws with regard to confounding adjustment and selection- and information bias. Conclusions Neither potential drivers of effectiveness nor an efficacy–effectiveness gap were identified. However, the limited number of studies and potential problems with confounding adjustment, selection- and information bias in the observational studies, may have hidden a true efficacy-effectiveness gap. PMID:28176959

Use of instrumental variables in the analysis of generalized linear models in the presence of unmeasured confounding with applications to epidemiological research.

PubMed

Johnston, K M; Gustafson, P; Levy, A R; Grootendorst, P

2008-04-30

A major, often unstated, concern of researchers carrying out epidemiological studies of medical therapy is the potential impact on validity if estimates of treatment are biased due to unmeasured confounders. One technique for obtaining consistent estimates of treatment effects in the presence of unmeasured confounders is instrumental variables analysis (IVA). This technique has been well developed in the econometrics literature and is being increasingly used in epidemiological studies. However, the approach to IVA that is most commonly used in such studies is based on linear models, while many epidemiological applications make use of non-linear models, specifically generalized linear models (GLMs) such as logistic or Poisson regression. Here we present a simple method for applying IVA within the class of GLMs using the generalized method of moments approach. We explore some of the theoretical properties of the method and illustrate its use within both a simulation example and an epidemiological study where unmeasured confounding is suspected to be present. We estimate the effects of beta-blocker therapy on one-year all-cause mortality after an incident hospitalization for heart failure, in the absence of data describing disease severity, which is believed to be a confounder. 2008 John Wiley & Sons, Ltd

Controlling for seasonal patterns and time varying confounders in time-series epidemiological models: a simulation study.

PubMed

Perrakis, Konstantinos; Gryparis, Alexandros; Schwartz, Joel; Le Tertre, Alain; Katsouyanni, Klea; Forastiere, Francesco; Stafoggia, Massimo; Samoli, Evangelia

2014-12-10

An important topic when estimating the effect of air pollutants on human health is choosing the best method to control for seasonal patterns and time varying confounders, such as temperature and humidity. Semi-parametric Poisson time-series models include smooth functions of calendar time and weather effects to control for potential confounders. Case-crossover (CC) approaches are considered efficient alternatives that control seasonal confounding by design and allow inclusion of smooth functions of weather confounders through their equivalent Poisson representations. We evaluate both methodological designs with respect to seasonal control and compare spline-based approaches, using natural splines and penalized splines, and two time-stratified CC approaches. For the spline-based methods, we consider fixed degrees of freedom, minimization of the partial autocorrelation function, and general cross-validation as smoothing criteria. Issues of model misspecification with respect to weather confounding are investigated under simulation scenarios, which allow quantifying omitted, misspecified, and irrelevant-variable bias. The simulations are based on fully parametric mechanisms designed to replicate two datasets with different mortality and atmospheric patterns. Overall, minimum partial autocorrelation function approaches provide more stable results for high mortality counts and strong seasonal trends, whereas natural splines with fixed degrees of freedom perform better for low mortality counts and weak seasonal trends followed by the time-season-stratified CC model, which performs equally well in terms of bias but yields higher standard errors. Copyright © 2014 John Wiley & Sons, Ltd.

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

PubMed

Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

2016-06-03

Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. 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/

Instrumental variable methods in comparative safety and effectiveness research†

PubMed Central

Brookhart, M. Alan; Rassen, Jeremy A.; Schneeweiss, Sebastian

2010-01-01

Summary Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial. PMID:20354968

Psychosocial Assessment of Self-Harm Patients and Risk of Repeat Presentation: An Instrumental Variable Analysis Using Time of Hospital Presentation.

PubMed

Carroll, Robert; Metcalfe, Chris; Steeg, Sarah; Davies, Neil M; Cooper, Jayne; Kapur, Nav; Gunnell, David

2016-01-01

Clinical guidelines have recommended psychosocial assessment of self-harm patients for years, yet estimates of its impact on the risk of repeat self-harm vary. Assessing the association of psychosocial assessment with risk of repeat self-harm is challenging due to the effects of confounding by indication. We analysed data from a cohort study of 15,113 patients presenting to the emergency departments of three UK hospitals to investigate the association of psychosocial assessment with risk of repeat hospital presentation for self-harm. Time of day of hospital presentation was used as an instrument for psychosocial assessment, attempting to control for confounding by indication. Conventional regression analysis suggested psychosocial assessment was not associated with risk of repeat self-harm within 12 months (Risk Difference (RD) 0.00 95% confidence interval (95%CI) -0.01 to 0.02). In contrast, IV analysis suggested risk of repeat self-harm was reduced by 18% (RD -0.18, 95%CI -0.32 to -0.03) in those patients receiving a psychosocial assessment. However, the instrument of time of day did not remove all potential effects of confounding by indication, suggesting the IV effect estimate may be biased. We found that psychosocial assessments reduce risk of repeat self-harm. This is in-line with other non-randomised studies based on populations in which allocation to assessment was less subject to confounding by indication. However, as our instrument did not fully balance important confounders across time of day, the IV effect estimate should be interpreted with caution.

Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls.

PubMed

Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R

2017-06-05

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. Published by Elsevier Ltd.

Outcome modelling strategies in epidemiology: traditional methods and basic alternatives

PubMed Central

Greenland, Sander; Daniel, Rhian; Pearce, Neil

2016-01-01

Abstract Controlling for too many potential confounders can lead to or aggravate problems of data sparsity or multicollinearity, particularly when the number of covariates is large in relation to the study size. As a result, methods to reduce the number of modelled covariates are often deployed. We review several traditional modelling strategies, including stepwise regression and the ‘change-in-estimate’ (CIE) approach to deciding which potential confounders to include in an outcome-regression model for estimating effects of a targeted exposure. We discuss their shortcomings, and then provide some basic alternatives and refinements that do not require special macros or programming. Throughout, we assume the main goal is to derive the most accurate effect estimates obtainable from the data and commercial software. Allowing that most users must stay within standard software packages, this goal can be roughly approximated using basic methods to assess, and thereby minimize, mean squared error (MSE). PMID:27097747

The Effects of Teacher Behaviors on Students' Inclination to Inquire and Lifelong Learning

ERIC Educational Resources Information Center

Loes, Chad N.; Saichaie, Kem; Padget, Ryan D.; Pascarella, Ernest T.

2012-01-01

This study estimated the effects of teacher organization, clarity, classroom challenge and faculty expectations, support, and prompt feedback on students' inclination to inquire and lifelong learning during the first year of college. Controlling for a battery of potential confounding influences, teacher organization was positively associated with…

Poppers, Kaposi's sarcoma, and HIV infection: empirical example of a strong confounding effect?

PubMed

Morabia, A

1995-01-01

Are there empirical examples of strong confounding effects? Textbooks usually show examples of weak confounding or use hypothetical examples of strong confounding to illustrate the paradoxical consequences of not separating out the effect of the studied exposure from that of second factor acting as a confounder. HIV infection is a candidate strong confounder of the spuriously high association reported between consumption of poppers, a sexual stimulant, and risk of Kaposi's sarcoma in the early phase of the AIDS epidemic. To examine this hypothesis, assumptions must be made on the prevalence of HIV infection among cases of Kaposi's sarcoma and on the prevalence of heavy popper consumption according to HIV infection in cases and controls. Results show that HIV infection may have confounded the poppers-Kaposi's sarcoma association. However, it cannot be ruled out that HIV did not qualify as a confounder because it was either an intermediate variable or an effect modifier of the association between popper inhalation and Kaposi's sarcoma. This example provides a basis to discuss the mechanism by which confounding occurs as well as the practical importance of confounding in epidemiologic research.

An epidemiological and toxicological evaluation of the carcinogenicity of man-made vitreous fiber, with a consideration of coexposures.

PubMed

Wong, O; Musselman, R P

1994-01-01

Exposure to man-made mineral (or vitreous) fiber (MMMF or MMVF) is a potential health concern in both occupational and environmental settings. Previous epidemiologic studies have reported a small increase of lung cancer among workers exposed to MMVF. Most of these studies were cohort studies and lacked information on fiber concentration, occupational coexposures, and cigarette smoking. Some of the coexposures were known human lung carcinogens and could have accounted for the small lung cancer excess. In a recently completed epidemiologic case-control study of lung cancer in MMVF workers exposed to slag wool fibers, we analyzed lung cancer risk in relation to cumulative fiber exposure (concentration and duration) and smoking history and controlled for other coexposures such as asbestos contamination. No increased lung cancer risk with exposure to slag wool fibers was found. As expected, however, we detected a strong confounding effect of smoking. The findings from this epidemiologic study were consistent with the results of recently completed toxicologic studies, which found that slag wool fibers of dimension classically associated with tumor induction ("Stanton" fibers) do not stay in the lung in sufficient quantity or time to induce tumors in animals. In this paper we emphasize the importance of confounding effects due to coexposures and provide guidelines to estimate the magnitude of potential confounding effects of coexposures such as smoking.

Confounding by dietary pattern of the inverse association between alcohol consumption and type 2 diabetes risk

USDA-ARS?s Scientific Manuscript database

Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as ...

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk

USDA-ARS?s Scientific Manuscript database

Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome this limitation. To examine confounding by dietary pattern as well as ...

Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

PubMed

Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

2017-01-01

Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

Association between age associated cognitive decline and health related quality of life among Iranian older individuals.

PubMed

Kazazi, Leila; Foroughan, Mahshid; Nejati, Vahid; Shati, Mohsen

2018-04-01

Age associated cognitive decline or normal cognitive aging is related with lower levels of functioning in real life, and may interfere with maintaining independence and health related quality of life (HRQL). In this study, health related quality of life and cognitive function in community-dwelling older adults were evaluated with the aim of exploring the association between them by adjusting for potential confounders. This cross-sectional study, was implemented on 425 community-dwelling older adults aged 60 and over, between August 2016 and October 2016 in health centers of the municipality of Tehran, Iran, using Mini Mental State Examination (MMSE) to assess cognitive function and Short Form-36 scales (SF-36) to assess HRQL. The relation between HRQL and cognitive function was evaluated by Pearson's correlation coefficient, and the impact of cognitive function on HRQL adjusted for potential confounders was estimated by linear regression model. All analyses were done using SPSS, version 22.0. A positive significant correlation between cognitive function and quality of life (r=0.434; p<0.001) and its dimensions was observed. Two variables of educational level (B=2.704; 95% CI: 2.09 to 3.30; p<0.001) and depression (B=2.554; 95% CI: 2.00 to 3.10; p<0.001) were assumed as potential confounder by changing effect measure after entering the model. After adjusting for potential confounders in regression model, the association between MMSE scores and quality of life persisted (B=2.417; 95% CI: 1.86 to 2.96; p<0.001). The results indicate that cognitive function was associated with HRQL in older adults with age associated cognitive function. Two variables of educational level and depression can affect the relation between cognitive decline and HRQL.

Associations between Responsible Beverage Service Laws and Binge Drinking and Alcohol-Impaired Driving

ERIC Educational Resources Information Center

Linde, Ann C.; Toomey, Traci L.; Wolfson, Julian; Lenk, Kathleen M.; Jones-Webb, Rhonda; Erickson, Darin J.

2016-01-01

We explored potential associations between the strength of state Responsible Beverage Service (RBS) laws and self-reported binge drinking and alcohol-impaired driving in the U.S. A multi-level logistic mixed-effects model was used, adjusting for potential confounders. Analyses were conducted on the overall BRFSS sample and drinkers only. Seven…

Residential proximity to electromagnetic field sources and birth weight: Minimizing residual confounding using multiple imputation and propensity score matching.

PubMed

de Vocht, Frank; Lee, Brian

2014-08-01

Studies have suggested that residential exposure to extremely low frequency (50 Hz) electromagnetic fields (ELF-EMF) from high voltage cables, overhead power lines, electricity substations or towers are associated with reduced birth weight and may be associated with adverse birth outcomes or even miscarriages. We previously conducted a study of 140,356 singleton live births between 2004 and 2008 in Northwest England, which suggested that close residential proximity (≤ 50 m) to ELF-EMF sources was associated with reduced average birth weight of 212 g (95%CI: -395 to -29 g) but not with statistically significant increased risks for other adverse perinatal outcomes. However, the cohort was limited by missing data for most potentially confounding variables including maternal smoking during pregnancy, which was only available for a small subgroup, while also residual confounding could not be excluded. This study, using the same cohort, was conducted to minimize the effects of these problems using multiple imputation to address missing data and propensity score matching to minimize residual confounding. Missing data were imputed using multiple imputation using chained equations to generate five datasets. For each dataset 115 exposed women (residing ≤ 50 m from a residential ELF-EMF source) were propensity score matched to 1150 unexposed women. After doubly robust confounder adjustment, close proximity to a residential ELF-EMF source remained associated with a reduction in birth weight of -116 g (95% confidence interval: -224:-7 g). No effect was found for proximity ≤ 100 m compared to women living further away. These results indicate that although the effect size was about half of the effect previously reported, close maternal residential proximity to sources of ELF-EMF remained associated with suboptimal fetal growth. Copyright © 2014 Elsevier Ltd. All rights reserved.

A flexible, interpretable framework for assessing sensitivity to unmeasured confounding.

PubMed

Dorie, Vincent; Harada, Masataka; Carnegie, Nicole Bohme; Hill, Jennifer

2016-09-10

When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-parameter sensitivity analysis strategy that assesses sensitivity of posterior distributions of treatment effects to choices of sensitivity parameters. This results in an easily interpretable framework for testing for the impact of an unmeasured confounder that also limits the number of modeling assumptions. We evaluate our approach in a large-scale simulation setting and with high blood pressure data taken from the Third National Health and Nutrition Examination Survey. The model is implemented as open-source software, integrated into the treatSens package for the R statistical programming language. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Hypothyroidism and carpal tunnel syndrome: a meta-analysis.

PubMed

Shiri, Rahman

2014-12-01

This study aimed to assess the magnitude of the association between hypothyroidism and carpal tunnel syndrome (CTS). Eighteen studies were included in a random-effects meta-analysis. A meta-analysis of the studies that did not control their estimates for any confounder showed an association between a thyroid disease (hypo- or hyperthyroidism) and CTS (N = 9,573, effect size [ES] = 1.32 (95% confidence interval [CI], 1.04-1.68) and between hypothyroidism and CTS (N = 64,531, ES = 2.15 [95% CI, 1.64-2.83]). When a meta-analysis limited to the studies that controlled their estimates for some potential confounders, the association between a thyroid disease and CTS disappeared (N = 4,799, ES = 1.17 [95% CI, 0.71-1.92], I(2) = 0%), and the effect size for hypothyroidism largely attenuated (N = 71,133, ES = 1.44 [95% CI, 1.27-1.63], I(2) = 0%). Moreover, there was evidence of publication bias. This meta-analysis found only a modest association between hypothyroidism and CTS. Confounding and publication bias may still account for part of the remaining excess risk. © 2014 Wiley Periodicals, Inc.

Using Ensemble-Based Methods for Directly Estimating Causal Effects: An Investigation of Tree-Based G-Computation

ERIC Educational Resources Information Center

Austin, Peter C.

2012-01-01

Researchers are increasingly using observational or nonrandomized data to estimate causal treatment effects. Essential to the production of high-quality evidence is the ability to reduce or minimize the confounding that frequently occurs in observational studies. When using the potential outcome framework to define causal treatment effects, one…

The Effects of Age on Second Language Grammar and Speech Production

ERIC Educational Resources Information Center

Huang, Becky H.

2014-01-01

The current study examined the age of learning effect on second language (L2) acquisition. The research goals of the study were twofold: to test whether there is an independent age effect controlling for other potentially confounding variables, and to clarify the age effect across L2 grammar and speech production domains. The study included 118…

Fortune Is Fickle: Null-Effects of Disfluency on Learning Outcomes

ERIC Educational Resources Information Center

Rummer, Ralf; Schweppe, Judith; Schwede, Annett

2016-01-01

Recently, Diemand-Yauman et al. "Cognition," 118, 114-118 (2011) demonstrated that learning with disfluent (hard-to-read) materials is more effective than learning with easy-to-read materials--a study that has since stipulated a number of follow-up studies (with mixed results). However, there is a potential confound in the original…

Effect of macronutrients and fiber on postprandial glycemic responses and meal glycemic index and glycemic load value determinations

USDA-ARS?s Scientific Manuscript database

Introduction: Meal or dietary glycemic index (GI) and glycemic load (GL) values from dietary questionnaires are calculated using GI values of individual foods and for GL after adjusting for serving size. Partially unaddressed is the potential confounding effect of different amounts and proportions o...

Assessing the impact of nano- and micro-scale zerovalent iron particles on soil microbial activities: particle reactivity interferes with assay conditions and interpretation of genuine microbial effects.

PubMed

Cullen, Laurence G; Tilston, Emma L; Mitchell, Geoff R; Collins, Chris D; Shaw, Liz J

2011-03-01

The effects of nano-scale and micro-scale zerovalent iron (nZVI and mZVI) particles on general (dehydrogenase and hydrolase) and specific (ammonia oxidation potential, AOP) activities mediated by the microbial community in an uncontaminated soil were examined. nZVI (diameter 12.5 nm; 10 mg g⁻¹ soil) apparently inhibited AOP and nZVI and mZVI apparently stimulated dehydrogenase activity but had minimal influence on hydrolase activity. Sterile experiments revealed that the apparent inhibition of AOP could not be interpreted as such due to the confounding action of the particles, whereas, the nZVI-enhanced dehydrogenase activity could represent the genuine response of a stimulated microbial population or an artifact of ZVI reactivity. Overall, there was no evidence for negative effects of nZVI or mZVI on the processes studied. When examining the impact of redox active particles such as ZVI on microbial oxidation-reduction reactions, potential confounding effects of the test particles on assay conditions should be considered. Copyright © 2010 Elsevier Ltd. All rights reserved.

An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

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

Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A.

2007-07-01

We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extentmore » to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.« less

Examining the Error of Mis-Specifying Nonlinear Confounding Effect with Application on Accelerometer-Measured Physical Activity

ERIC Educational Resources Information Center

Lee, Paul H.

2017-01-01

Purpose: Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. Methods: We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the…

Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

ERIC Educational Resources Information Center

Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

2016-01-01

A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

Examining the Error of Mis-Specifying Nonlinear Confounding Effect With Application on Accelerometer-Measured Physical Activity.

PubMed

Lee, Paul H

2017-06-01

Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the estimation of a causal relationship between the exposure and outcome in 3 ways: using a linear term, binning into 5 equal-size categories, or using a restricted cubic spline of the confounder. Continuous, binary, and survival outcomes were simulated. We examined the confounder across varying measurement error. In addition, we performed a real data analysis examining the 3 strategies to handle the nonlinear effects of accelerometer-measured physical activity in the National Health and Nutrition Examination Survey 2003-2006 data. The mis-specification of a nonlinear confounder had little impact on causal effect estimation for continuous outcomes. For binary and survival outcomes, this mis-specification introduced bias, which could be eliminated using spline adjustment only when there is small measurement error of the confounder. Real data analysis showed that the associations between high blood pressure, high cholesterol, and diabetes and mortality adjusted for physical activity with restricted cubic spline were about 3% to 11% larger than their counterparts adjusted with a linear term. For continuous outcomes, confounders with nonlinear effects can be adjusting with a linear term. Spline adjustment should be used for binary and survival outcomes on confounders with small measurement error.

Comparison of methods for the analysis of relatively simple mediation models.

PubMed

Rijnhart, Judith J M; Twisk, Jos W R; Chinapaw, Mai J M; de Boer, Michiel R; Heymans, Martijn W

2017-09-01

Statistical mediation analysis is an often used method in trials, to unravel the pathways underlying the effect of an intervention on a particular outcome variable. Throughout the years, several methods have been proposed, such as ordinary least square (OLS) regression, structural equation modeling (SEM), and the potential outcomes framework. Most applied researchers do not know that these methods are mathematically equivalent when applied to mediation models with a continuous mediator and outcome variable. Therefore, the aim of this paper was to demonstrate the similarities between OLS regression, SEM, and the potential outcomes framework in three mediation models: 1) a crude model, 2) a confounder-adjusted model, and 3) a model with an interaction term for exposure-mediator interaction. Secondary data analysis of a randomized controlled trial that included 546 schoolchildren. In our data example, the mediator and outcome variable were both continuous. We compared the estimates of the total, direct and indirect effects, proportion mediated, and 95% confidence intervals (CIs) for the indirect effect across OLS regression, SEM, and the potential outcomes framework. OLS regression, SEM, and the potential outcomes framework yielded the same effect estimates in the crude mediation model, the confounder-adjusted mediation model, and the mediation model with an interaction term for exposure-mediator interaction. Since OLS regression, SEM, and the potential outcomes framework yield the same results in three mediation models with a continuous mediator and outcome variable, researchers can continue using the method that is most convenient to them.

If it is published in the peer-reviewed literature, it must be true?

PubMed

Wagner, Louis K

2014-10-01

Epidemiological research correlating cancer rates in a population of patients with radiation doses from medical X-rays is fraught with confounding factors that obfuscate the likelihood that any positive relationship is causal. This is a review of four studies involving some of those confounding factors. Comparisons of findings with other studies not encumbered by similar confounding factors can enhance assertions of causation between medical X-rays and cancer rates. Even so, such assertions rest significantly on opinions of researchers regarding the degree of consistency between findings among various studies. The question as to what degree any findings truly represent cause and effect will likely still meet with controversy. The importance of these findings to medicine should therefore not lie in any controversy regarding causation, but in what the findings potentially mean with regard to benefit and risk for patients and the professional practice of medicine.

A Study to Determine if Pharmaceutical Cost is Related to Diagnostic Complexity for the Treatment of Essential Hypertension Patients at Womack Army Community Hospital

DTIC Science & Technology

1987-05-01

angiotensin without actually measuring sodium electrolyte levels), and pancreatic disease (to remove potential confounding effects of diabetes ...side effects such as muscle weakness, polyuria and an increased propensity toward cardiac arrhythmias. When uric acid (UA) levels increase to 6.0 mg per

Theoretical Basis of the Test-Negative Study Design for Assessment of Influenza Vaccine Effectiveness

PubMed Central

Sullivan, Sheena G.; Tchetgen Tchetgen, Eric J.; Cowling, Benjamin J.

2016-01-01

Influenza viruses undergo frequent antigenic changes. As a result, the viruses circulating change within and between seasons, and the composition of the influenza vaccine is updated annually. Thus, estimation of the vaccine's effectiveness is not constant across seasons. In order to provide annual estimates of the influenza vaccine's effectiveness, health departments have increasingly adopted the “test-negative design,” using enhanced data from routine surveillance systems. In this design, patients presenting to participating general practitioners with influenza-like illness are swabbed for laboratory testing; those testing positive for influenza virus are defined as cases, and those testing negative form the comparison group. Data on patients' vaccination histories and confounder profiles are also collected. Vaccine effectiveness is estimated from the odds ratio comparing the odds of testing positive for influenza among vaccinated patients and unvaccinated patients, adjusting for confounders. The test-negative design is purported to reduce bias associated with confounding by health-care-seeking behavior and misclassification of cases. In this paper, we use directed acyclic graphs to characterize potential biases in studies of influenza vaccine effectiveness using the test-negative design. We show how studies using this design can avoid or minimize bias and where bias may be introduced with particular study design variations. PMID:27587721

Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

PubMed

Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R

2016-12-01

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

PubMed

Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

2012-01-02

In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

PubMed Central

Källén, Bengt

2012-01-01

In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes. PMID:22190949

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls.

PubMed

Simon, Naomi M; Walton, Zandra E; Bui, Eric; Prescott, Jennifer; Hoge, Elizabeth; Keshaviah, Aparna; Schwarz, Noah; Dryman, Taylor; Ojserkis, Rebecca A; Kovachy, Benjamin; Mischoulon, David; Worthington, John; De Vivo, Immaculata; Fava, Maurizio; Wong, Kwok-Kin

2015-08-01

Leukocyte telomere length (LTL) is a marker of cellular turnover and oxidative stress. Studies suggest major depressive disorder (MDD) is associated with oxidative stress, but examinations of MDD and LTL have yielded mixed results, likely because of differences in measurement methods and unmeasured confounding. This study examined LTL and telomerase activity in 166 individuals with MDD compared to 166 age- and gender-matched matched controls free of any psychiatric disorder, using well-validated assays and clinical assessment methods, and controlling for a range of potential confounders. Subjects aged 18 to 70 were evaluated by trained raters and provided blood for LTL and telomerase activity measurement. LTL was assayed using Southern blot and replicated with qPCR, and telomerase activity was assayed with a repeat amplification protocol using a commercial kit. There was no significant difference in telomere length for individuals with MDD [mean (SD)=9.1 (3.0)kbp] compared to controls [mean(SD)=8.9(2.5)kbp] measured by Southern blot (p=0.65) or by confirmatory qPCR (p=0.91) assays. Controlling for potential confounders did not alter the results. Telomerase activity did not differ by MDD diagnosis overall (p=0.40), but the effect of MDD was significantly modified by gender (t(299)=2.67, p=0.0079) even after controlling for potential confounders, with telomerase activity significantly greater only in males with MDD versus controls. Our well-characterized, well-powered examination of concurrently assessed telomere length and telomerase activity in individuals with clinically significant, chronic MDD and matched controls failed to provide strong evidence of an association of MDD with shorter LTL, while telomerase activity was higher in men with MDD [corrected]. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sensitivity analysis for direct and indirect effects in the presence of exposure-induced mediator-outcome confounders

PubMed Central

Chiba, Yasutaka

2014-01-01

Questions of mediation are often of interest in reasoning about mechanisms, and methods have been developed to address these questions. However, these methods make strong assumptions about the absence of confounding. Even if exposure is randomized, there may be mediator-outcome confounding variables. Inference about direct and indirect effects is particularly challenging if these mediator-outcome confounders are affected by the exposure because in this case these effects are not identified irrespective of whether data is available on these exposure-induced mediator-outcome confounders. In this paper, we provide a sensitivity analysis technique for natural direct and indirect effects that is applicable even if there are mediator-outcome confounders affected by the exposure. We give techniques for both the difference and risk ratio scales and compare the technique to other possible approaches. PMID:25580387

Assessment of Confounders in Comparative Effectiveness Studies From Secondary Databases.

PubMed

Franklin, Jessica M; Schneeweiss, Sebastian; Solomon, Daniel H

2017-03-15

Secondary clinical databases are an important and growing source of data for comparative effectiveness research (CER) studies. However, measurement of confounders, such as biomarker values or patient-reported health status, in secondary clinical databases may not align with the initiation of a new treatment. In many published CER analyses of registry data, investigators assessed confounders based on the first questionnaire in which the new exposure was recorded. However, it is known that adjustment for confounders measured after the start of exposure can lead to biased treatment effect estimates. In the present study, we conducted simulations to compare assessment strategies for a dynamic clinical confounder in a registry-based comparative effectiveness study of 2 therapies. As expected, we found that adjustment for the confounder value at the time of the first questionnaire after the start of exposure creates a biased estimate the total effect of exposure choice on outcome when the confounder mediates part of the effect. However, adjustment for the prior value can also be badly biased when measured long before exposure initiation. Thus, investigators should carefully consider the timing of confounder measurements relative to exposure initiation and the rate of change in the confounder in order to choose the most relevant measure for each patient. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Effects of Fraternity and Sorority Membership in the Fourth Year of College: A Detrimental or Value-Added Component of Undergraduate Education?

ERIC Educational Resources Information Center

Hevel, Michael S.; Martin, Georgianna L.; Weeden, Dustin D.; Pascarella, Ernest T.

2015-01-01

We use a longitudinal national dataset to explore the direct and conditional effects of fraternity/sorority membership on students' educational outcomes in the 4th year of college. Controlling for a variety of potentially confounding variables, including pretest measures of the outcomes, we find no direct effect of fraternity/sorority membership…

Sample size calculations for case-control studies

Cancer.gov

This R package can be used to calculate the required samples size for unconditional multivariate analyses of unmatched case-control studies. The sample sizes are for a scalar exposure effect, such as binary, ordinal or continuous exposures. The sample sizes can also be computed for scalar interaction effects. The analyses account for the effects of potential confounder variables that are also included in the multivariate logistic model.

Diagnostics for Confounding of Time-varying and Other Joint Exposures.

PubMed

Jackson, John W

2016-11-01

The effects of joint exposures (or exposure regimes) include those of adhering to assigned treatment versus placebo in a randomized controlled trial, duration of exposure in a cohort study, interactions between exposures, and direct effects of exposure, among others. Unlike the setting of a single point exposure (e.g., propensity score matching), there are few tools to describe confounding for joint exposures or how well a method resolves it. Investigators need tools that describe confounding in ways that are conceptually grounded and intuitive for those who read, review, and use applied research to guide policy. We revisit the implications of exchangeability conditions that hold in sequentially randomized trials, and the bias structure that motivates the use of g-methods, such as marginal structural models. From these, we develop covariate balance diagnostics for joint exposures that can (1) describe time-varying confounding, (2) assess whether covariates are predicted by prior exposures given their past, the indication for g-methods, and (3) describe residual confounding after inverse probability weighting. For each diagnostic, we present time-specific metrics that encompass a wide class of joint exposures, including regimes of multivariate time-varying exposures in censored data, with multivariate point exposures as a special case. We outline how to estimate these directly or with regression and how to average them over person-time. Using a simulated example, we show how these metrics can be presented graphically. This conceptually grounded framework can potentially aid the transparent design, analysis, and reporting of studies that examine joint exposures. We provide easy-to-use tools to implement it.

DIFFERENCES IN STEROID MEASUREMENTS FOLLOWING ADULT AND HATCHLING EXPOSURE TO THE PHYTOESTROGEN APIGENIN

EPA Science Inventory

Weak estrogens, such as those produced by plants, may comprise the majority of the total estrogen load in exposed populations. Because of
their potential to produce confounding estrogenic and anti-estrogenic effects in competition with endogenous estradiol, several questions

Effect of water potential and void ratio on erodibility for agricultural soils

USDA-ARS?s Scientific Manuscript database

Soil erodibility has confounded researchers for decades. Difficulties arise with initiation of motion, pore-water status, physical, and perhaps biological, material properties and type of applied energy (i.e. rainfall, runoff, freeze/thaw, wind). Though specific tests have been developed to determin...

Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.

PubMed

Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M; Langbehn, Doug R; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J

2016-01-11

 Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.

The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions.

PubMed

Gemmell, Isla; Dunn, Graham

2011-03-01

In a partially randomized preference trial (PRPT) patients with no treatment preference are allocated to groups at random, but those who express a preference receive the treatment of their choice. It has been suggested that the design can improve the external and internal validity of trials. We used computer simulation to illustrate the impact that an unmeasured confounder could have on the results and conclusions drawn from a PRPT. We generated 4000 observations ("patients") that reflected the distribution of the Beck Depression Index (DBI) in trials of depression. Half were randomly assigned to a randomized controlled trial (RCT) design and half were assigned to a PRPT design. In the RCT, "patients" were evenly split between treatment and control groups; whereas in the preference arm, to reflect patient choice, 87.5% of patients were allocated to the experimental treatment and 12.5% to the control. Unadjusted analyses of the PRPT data consistently overestimated the treatment effect and its standard error. This lead to Type I errors when the true treatment effect was small and Type II errors when the confounder effect was large. The PRPT design is not recommended as a method of establishing an unbiased estimate of treatment effect due to the potential influence of unmeasured confounders. Copyright © 2011 John Wiley & Sons, Ltd.

Effects of psychosocial work factors on lifestyle changes: a cohort study.

PubMed

Allard, Karin Olofsson; Thomsen, Jane Frølund; Mikkelsen, Sigurd; Rugulies, Reiner; Mors, Ole; Kærgaard, Anette; Kolstad, Henrik A; Kaerlev, Linda; Andersen, Johan Hviid; Hansen, Ase Marie; Bonde, Jens Peter

2011-12-01

To evaluate the effect of the demand-control-support model, the effort-reward imbalance model, and emotional demands on smoking, alcohol consumption, physical activity, and body mass index. This is a 2-year prospective cohort study of 3224 public sector employees. Measures were assessed with questionnaires. Multiple regression analyses were used to predict changes in lifestyle factors. Low reward predicted smoking, low-decision latitude predicted being inactive, and high demands predicted high-alcohol consumption but only for men at follow-up even after controlling for potential confounders. There were no other significant findings in the expected direction except for some of the confounders. We found only limited and inconsistent support for the hypothesis that a poor psychosocial work environment is associated with an adverse lifestyle.

Do Fraternities and Sororities Still Enhance Socially Responsible Leadership? Evidence from the Fourth Year of College

ERIC Educational Resources Information Center

Hevel, Michael S.; Martin, Georgianna L.; Pascarella, Ernest T.

2014-01-01

We use a longitudinal national dataset to explore the effects of fraternity and sorority membership on students' socially responsible leadership in the fourth year of college. Controlling for a variety of potentially confounding variables, we find no net effect. These findings run counter to an earlier study based on the same students that found…

Effects of coffee consumption on glucose tolerance, serum glucose and insulin levels--a cross-sectional analysis.

PubMed

Bidel, S; Hu, G; Sundvall, J; Kaprio, J; Tuomilehto, J

2006-01-01

Coffee has several metabolic effects that could reduce the risk of type 2 diabetes. Our objective was to examine the effects of coffee consumption on glucose tolerance, glucose and insulin levels. A subsample of subjects aged 45 to 64 years in 1987 and in 1992 from the population-based FINRISK study (12,287 individuals) was invited to receive the standard oral glucose tolerance test at baseline. Plasma samples were taken after an overnight fast, and a two-hour oral glucose tolerance test was administered. Fasting and two-hour plasma glucose and insulin were measured in 2434 subjects with data on coffee use and potential confounders. After adjustment for potential confounding factors (age, body mass index, systolic blood pressure, occupational, commuting and leisure time physical activity, alcohol and tea drinking, smoking), coffee consumption was significantly and inversely associated with fasting glucose, two-hour plasma glucose, and fasting insulin in both men and women. Coffee consumption was significantly and inversely associated with impaired fasting glucose, impaired glucose regulation, and hyperinsulinemia among both men and women and with isolated impaired glucose tolerance among women. In this cross-sectional analysis, coffee showed positive effects on several glycemia markers.

The Conservative Corner of the Liberal Academy? Fraternity/Sorority Membership, Politics, and Activism

ERIC Educational Resources Information Center

Hevel, Michael S.; Weeden, Dustin D.; Pasquesi, Kira; Pascarella, Ernest T.

2015-01-01

We use a longitudinal dataset to explore the effect of fraternity/sorority membership on political orientation and social/political activism. After controlling for a variety of potentially confounding variables, including pretests on the dependent variables, fraternity and sorority members were significantly less liberal that their unaffiliated…

Measuring Systematic Long-Term Trajectories of School Effectiveness Improvement

ERIC Educational Resources Information Center

Valenzuela, Juan Pablo; Bellei, Cristián; Allende, Claudio

2016-01-01

The objective of this study was to identify trajectories of school improvement experienced by Chilean elementary schools over the last decade. Using econometric analysis and controlling for potential confounding factors, we created an index of school performance combining outcome indicators focused on different school dimensions, and estimated the…

Epidemiologic methods in clinical trials.

PubMed

Rothman, K J

1977-04-01

Epidemiologic methods developed to control confounding in non-experimental studies are equally applicable for experiments. In experiments, most confounding is usually controlled by random allocation of subjects to treatment groups, but randomization does not preclude confounding except for extremely large studies, the degree of confounding expected being inversely related to the size of the treatment groups. In experiments, as in non-experimental studies, the extent of confounding for each risk indicator should be assessed, and if sufficiently large, controlled. Confounding is properly assessed by comparing the unconfounded effect estimate to the crude effect estimate; a common error is to assess confounding by statistical tests of significance. Assessment of confounding involves its control as a prerequisite. Control is most readily and cogently achieved by stratification of the data, though with many factors to control simultaneously, multivariate analysis or a combination of multivariate analysis and stratification might be necessary.

Cardiovascular health, traffic-related air pollution and noise: are associations mutually confounded? A systematic review.

PubMed

Tétreault, Louis-François; Perron, Stéphane; Smargiassi, Audrey

2013-10-01

This review assessed the confounding effect of one traffic-related exposure (noise or air pollutants) on the association between the other exposure and cardiovascular outcomes. A systematic review was conducted with the databases Medline and Embase. The confounding effects in studies were assessed by using change in the estimate with a 10 % cutoff point. The influence on the change in the estimate of the quality of the studies, the exposure assessment methods and the correlation between road noise and air pollutions were also assessed. Nine publications were identified. For most studies, the specified confounders produced changes in estimates <10 %. The correlation between noise and pollutants, the quality of the study and of the exposure assessment do not seem to influence the confounding effects. Results from this review suggest that confounding of cardiovascular effects by noise or air pollutants is low, though with further improvements in exposure assessment, the situation may change. More studies using pollution indicators specific to road traffic are needed to properly assess if noise and air pollution are subjected to confounding.

Visual search for emotional expressions: Effect of stimulus set on anger and happiness superiority.

PubMed

Savage, Ruth A; Becker, Stefanie I; Lipp, Ottmar V

2016-01-01

Prior reports of preferential detection of emotional expressions in visual search have yielded inconsistent results, even for face stimuli that avoid obvious expression-related perceptual confounds. The current study investigated inconsistent reports of anger and happiness superiority effects using face stimuli drawn from the same database. Experiment 1 excluded procedural differences as a potential factor, replicating a happiness superiority effect in a procedure that previously yielded an anger superiority effect. Experiments 2a and 2b confirmed that image colour or poser gender did not account for prior inconsistent findings. Experiments 3a and 3b identified stimulus set as the critical variable, revealing happiness or anger superiority effects for two partially overlapping sets of face stimuli. The current results highlight the critical role of stimulus selection for the observation of happiness or anger superiority effects in visual search even for face stimuli that avoid obvious expression related perceptual confounds and are drawn from a single database.

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk.

PubMed

Imamura, Fumiaki; Lichtenstein, Alice H; Dallal, Gerard E; Meigs, James B; Jacques, Paul F

2009-07-01

The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of > or =9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.

Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study.

PubMed

Paganini-Hill, Annlia; Kawas, Claudia H; Corrada, María M

2007-04-01

To examine the effects of non-alcoholic beverage and caffeine consumption on all-cause mortality in older adults. The Leisure World Cohort Study is a prospective study of residents of a California retirement community. A baseline postal health survey included details on coffee, tea, milk, soft drink, and chocolate consumption. Participants were followed for 23 years (1981-2004). Risk ratios (RRs) of death were calculated using Cox regression for 8644 women and 4980 men (median age at entry, 74 years) and adjusted for age, gender, and multiple potential confounders. Caffeine consumption exhibited a U-shaped mortality curve. Moderate caffeine consumers had a significantly reduced risk of death (multivariable-adjusted RR=0.94, 95% CI: 0.89, 0.99 for 100-199 mg/day and RR=0.90, 95% CI: 0.85, 0.94 for 200-399 mg/day compared with those consuming <50 mg/day). Individuals who drank more than 1 can/week of artificially sweetened (but not sugar-sweetened) soft drink (cola and other) had an 8% increased risk (95% CI: 1.01-1.16). Neither milk nor tea had a significant effect on mortality after multivariable adjustment. Moderate caffeine consumption appeared beneficial in reducing risk of death. Attenuation in the observed associations between mortality and intake of tea and milk with adjustment for potential confounders suggests that such consumption identifies those with other mortality-associated lifestyle and health risks. The increased death risk with consumption of artificially sweetened, but not sugar-sweetened, soft drinks suggests an effect of the sweetener rather than other components of the soft drinks, although residual confounding remains a possibility.

Working on Sundays–effects on safety, health, and work-life balance.

PubMed

Wirtz, Anna; Nachreiner, Friedhelm; Rolfes, Katharina

2011-05-01

Several attributes of the work schedule can increase the risk of occupational injuries and accidents, health impairments, and reduced social participation. Although previous studies mainly focused on the effects of shiftwork and long working hours on employee health and safety, there is little evidence of a potential negative impact of working Sundays on the incidence of occupational accidents, health impairments, and work-life balance. A representative sample of employed workers in 31 member and associated states of the European Union (n = 23,934) served as the database for a cross-sectional analysis. The sample was collected via face-to-face interviews in the year 2005. The association of the risks of occupational accidents, health impairments, and decreases in work-life balance with working Sundays was calculated using logistic regression models, controlling for potential confounders, such as shiftwork, workload, and demographic characteristics. The results indicated that working one or more Sundays/month was associated with increase both in the risk of reporting one or more health impairments (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.06-1.29) and poorer work-life balance (OR: 1.15, 95% CI: 1.02-1.28). These effects remained after controlling for potentially confounding factors, such as other work schedule attributes, intensity of physical and mental workload, and individual characteristics. Furthermore, working Sundays was also related to increased risk of occupational accidents within the last year (OR: 1.34, 95% CI: 1.03-1.73). Controlling again for individual, workload, and working-time characteristics, a significant association with accident risk, however, remained only in work sectors with low a priori risk of occupational accidents (OR: 1.40, 95% CI: 1.02-1.91), although the increased risk could be observed for both medium and high a priori risk sectors working Sundays (without controlling for additional confounders). The results thus indicate that the detrimental effects of working Sundays on safety, health, and social well-being should be taken into account when designing work schedules. The potential hazards to employees' safety, health, and work-life balance, in particular, should be considered in discussions concerning extending work on Sundays in certain sectors, e.g., retail.

Coping with confounds in multivoxel pattern analysis: what should we do about reaction time differences? A comment on Todd, Nystrom & Cohen 2013.

PubMed

Woolgar, Alexandra; Golland, Polina; Bode, Stefan

2014-09-01

Multivoxel pattern analysis (MVPA) is a sensitive and increasingly popular method for examining differences between neural activation patterns that cannot be detected using classical mass-univariate analysis. Recently, Todd et al. ("Confounds in multivariate pattern analysis: Theory and rule representation case study", 2013, NeuroImage 77: 157-165) highlighted a potential problem for these methods: high sensitivity to confounds at the level of individual participants due to the use of directionless summary statistics. Unlike traditional mass-univariate analyses where confounding activation differences in opposite directions tend to approximately average out at group level, group level MVPA results may be driven by any activation differences that can be discriminated in individual participants. In Todd et al.'s empirical data, factoring out differences in reaction time (RT) reduced a classifier's ability to distinguish patterns of activation pertaining to two task rules. This raises two significant questions for the field: to what extent have previous multivoxel discriminations in the literature been driven by RT differences, and by what methods should future studies take RT and other confounds into account? We build on the work of Todd et al. and compare two different approaches to remove the effect of RT in MVPA. We show that in our empirical data, in contrast to that of Todd et al., the effect of RT on rule decoding is negligible, and results were not affected by the specific details of RT modelling. We discuss the meaning of and sensitivity for confounds in traditional and multivoxel approaches to fMRI analysis. We observe that the increased sensitivity of MVPA comes at a price of reduced specificity, meaning that these methods in particular call for careful consideration of what differs between our conditions of interest. We conclude that the additional complexity of the experimental design, analysis and interpretation needed for MVPA is still not a reason to favour a less sensitive approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Overview of potential procedural and participant-related confounds for neuroimaging of the resting state

PubMed Central

Duncan, Niall W.; Northoff, Georg

2013-01-01

Studies of intrinsic brain activity in the resting state have become increasingly common. A productive discussion of what analysis methods are appropriate, of the importance of physiologic correction and of the potential interpretations of results has been ongoing. However, less attention has been paid to factors other than physiologic noise that may confound resting-state experiments. These range from straightforward factors, such as ensuring that participants are all instructed in the same manner, to more obscure participant-related factors, such as body weight. We provide an overview of such potentially confounding factors, along with some suggested approaches for minimizing their impact. A particular theme that emerges from the overview is the range of systematic differences between types of study groups (e.g., between patients and controls) that may influence resting-state study results. PMID:22964258

Physical work load and psychological stress of daily activities as predictors of disability pension due to musculoskeletal disorders.

PubMed

Ropponen, Annina; Svedberg, Pia; Koskenvuo, Markku; Silventoinen, Karri; Kaprio, Jaakko

2014-06-01

Physical work loading and psychological stress commonly co-occur in working life, hence potentially having an interrelationship that may affect work incapacity. This prospective cohort study aimed to investigate the effect of stability and change in physical work loading and stress on the risk of disability pension (DP) due to musculoskeletal diagnoses (MSD), while accounting for familial confounding in these associations. Data on 12,455 twins born before 1958 were surveyed of their physical work loading and psychological stress of daily activities in 1975 and 1981. The follow-up data was collected from pension registers until 2004. Cox proportional hazards regression models were used. During the follow up, 893 participants were granted DP due to MSD. Stable high (hazard ratio, HR, 2.21), but also increased physical work loading (HR 2.05) and high psychological stress (HR 2.22) were associated with increased risk for DP, and had significant interaction (p=0.032). The associations were confirmed when accounting for several confounding factors. Stable high but also increased physical work loading and psychological stress of daily activities between two timepoints with 6 years apart confirms their predictive role for an increased risk of DP. Both physical work loading and psychological stress seem to be independent from various confounding factors hence suggesting direct effect on risk for DP providing potential for occupational health care to early identification of persons at risk. © 2014 the Nordic Societies of Public Health.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis

PubMed Central

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L.; Chen, Lin S.

2017-01-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is “mediation” by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are “cis-mediators” of trans-eQTLs, including those “cis-hubs” involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types. PMID:29021290

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

PubMed

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

Psychotic experiences and risk of self-injurious behaviour in the general population: a systematic review and meta-analysis.

PubMed

Honings, S; Drukker, M; Groen, R; van Os, J

2016-01-01

Recent studies suggest that psychotic experiences (PE) in the general population are associated with an increased risk of self-injurious behaviour. Both the magnitude of this association and the level of adjustment for confounders vary among studies. A meta-analysis was performed to integrate the available evidence. The influence of possible confounders, including variably defined depression, was assessed. A systematic review and meta-analysis was conducted including general population studies reporting on the risk of self-injurious behaviour in individuals with PE. Studies were identified by a systematic search strategy in Pubmed, PsycINFO and Embase. Reported effect sizes were extracted and meta-analytically pooled. The risk of self-injurious behaviour was 3.20 times higher in individuals with PE compared with those without. Subanalyses showed that PE were associated with self-harm, suicidal ideation as well as suicidal attempts. All studies had scope for considerable residual confounding; effect sizes adjusted for depression were significantly smaller than effect sizes unadjusted for depression. In the longitudinal studies, adjustment for psychopathology resulted in a 74% reduction in excess risk. PE are associated with self-injurious behaviour, suggesting they have potential as passive markers of suicidality. However, the association is confounded and several methodological issues remain, particularly how to separate PE from the full range of connected psychopathology in determining any specific association with self-injurious behaviour. Given evidence that PE represent an indicator of severity of non-psychotic psychopathology, the association between PE and self-injurious behaviour probably reflects a greater likelihood of self-injurious behaviour in more severe states of mental distress.

Examining the role of unmeasured confounding in mediation analysis with genetic and genomic applications.

PubMed

Lutz, Sharon M; Thwing, Annie; Schmiege, Sarah; Kroehl, Miranda; Baker, Christopher D; Starling, Anne P; Hokanson, John E; Ghosh, Debashis

2017-07-19

In mediation analysis if unmeasured confounding is present, the estimates for the direct and mediated effects may be over or under estimated. Most methods for the sensitivity analysis of unmeasured confounding in mediation have focused on the mediator-outcome relationship. The Umediation R package enables the user to simulate unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships in order to see how the results of the mediation analysis would change in the presence of unmeasured confounding. We apply the Umediation package to the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study to examine the role of unmeasured confounding due to population stratification on the effect of a single nucleotide polymorphism (SNP) in the CHRNA5/3/B4 locus on pulmonary function decline as mediated by cigarette smoking. Umediation is a flexible R package that examines the role of unmeasured confounding in mediation analysis allowing for normally distributed or Bernoulli distributed exposures, outcomes, mediators, measured confounders, and unmeasured confounders. Umediation also accommodates multiple measured confounders, multiple unmeasured confounders, and allows for a mediator-exposure interaction on the outcome. Umediation is available as an R package at https://github.com/SharonLutz/Umediation A tutorial on how to install and use the Umediation package is available in the Additional file 1.

Peer influence as a potential magnifier of ADHD diagnosis.

PubMed

Aronson, Brian

2016-11-01

The prevalence of Attention Deficit and Hyperactivity Disorder (ADHD) is growing in America, but its cause is unclear. Scholars have identified many environmental factors that can cause or confound ADHD diagnosis, but epidemiological studies that try to control for confounding factors still find evidence that rates of ADHD diagnosis are increasing. As a preliminary explanation to ADHD's increasing prevalence, this article examines whether core ADHD diagnostic traits are subject to peer influence. If ADHD diagnosis can be confounded by peer influence, there are several mechanisms that could have caused increased rates of diagnosis. With data drawn from two schools across three waves in the National Longitudinal Survey of Adolescent Health (n = 2193), the author uses a stochastic actor oriented model to estimate the effect of peer influence on inattention, controlling for alternative network and behavioral causes. Results indicate that respondents have a strong likelihood to modify their self-reports of inattention, a core ADHD trait, to resemble that of their friends. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does Pollution Increase School Absences? NBER Working Paper No. 13252

ERIC Educational Resources Information Center

Currie, Janet; Hanushek, Eric; Kahn, E. Megan; Neidell, Matthew; Rivkin, Steven

2007-01-01

We examine the effect of air pollution on school absences using unique administrative data for elementary and middle school children in the 39 largest school districts in Texas. These data are merged with information from monitors maintained by the Environmental Protection Agency. To control for potentially confounding factors, we adopt a…

Adolescent Substance Use, Sleep, and Academic Achievement: Evidence of Harm Due to Caffeine

ERIC Educational Resources Information Center

James, Jack E.; Kristjansson, Alfgeir Logi; Sigfusdottir, Inga Dora

2011-01-01

Using academic achievement as the key outcome variable, 7377 Icelandic adolescents were surveyed for cigarette smoking, alcohol use, daytime sleepiness, caffeine use, and potential confounders. Structural equation modeling (SEM) was used to examine direct and indirect effects of measured and latent variables in two models: the first with caffeine…

Maternal smoking during pregnancy and children's cognitive and physical development: a causal risk factor?

PubMed

Gilman, Stephen E; Gardener, Hannah; Buka, Stephen L

2008-09-01

There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959-1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of -85.63 g associated with smoking of >or=20 cigarettes daily during pregnancy (95% confidence interval: -131.91, -39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking.

Stratification for the propensity score compared with linear regression techniques to assess the effect of treatment or exposure.

PubMed

Senn, Stephen; Graf, Erika; Caputo, Angelika

2007-12-30

Stratifying and matching by the propensity score are increasingly popular approaches to deal with confounding in medical studies investigating effects of a treatment or exposure. A more traditional alternative technique is the direct adjustment for confounding in regression models. This paper discusses fundamental differences between the two approaches, with a focus on linear regression and propensity score stratification, and identifies points to be considered for an adequate comparison. The treatment estimators are examined for unbiasedness and efficiency. This is illustrated in an application to real data and supplemented by an investigation on properties of the estimators for a range of underlying linear models. We demonstrate that in specific circumstances the propensity score estimator is identical to the effect estimated from a full linear model, even if it is built on coarser covariate strata than the linear model. As a consequence the coarsening property of the propensity score-adjustment for a one-dimensional confounder instead of a high-dimensional covariate-may be viewed as a way to implement a pre-specified, richly parametrized linear model. We conclude that the propensity score estimator inherits the potential for overfitting and that care should be taken to restrict covariates to those relevant for outcome. Copyright (c) 2007 John Wiley & Sons, Ltd.

Why Do Thin People Have Elevated All-Cause Mortality? Evidence on Confounding and Reverse Causality in the Association of Adiposity and COPD from the British Women’s Heart and Health Study

PubMed Central

Dale, Caroline; Nüesch, Eveline; Prieto-Merino, David; Choi, Minkyoung; Amuzu, Antoinette; Ebrahim, Shah; Casas, Juan P.; Davey-Smith, George

2015-01-01

Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women’s Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3 – 3.1 versus OR = 1.2; 95% CI 0.7 – 1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding. PMID:25884834

Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

PubMed

O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

2011-12-01

When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study

PubMed Central

Paganini-Hill, Annlia; Kawas, Claudia H; Corrada, María M

2007-01-01

Objective To examine the effects of non-alcoholic beverage and caffeine consumption on all-cause mortality in older adults. Methods The Leisure World Cohort Study is a prospective study of residents of a California retirement community. A baseline postal health survey included details on coffee, tea, milk, soft drink, and chocolate consumption. Participants were followed for 23 years (1981–2004). Risk ratios (RRs) of death were calculated using Cox regression for 8644 women and 4980 men (median age at entry, 74 years) and adjusted for age, gender and multiple potential confounders. Results Caffeine consumption exhibited a U-shaped mortality curve. Moderate caffeine consumers had a significantly reduced risk of death (multivariable-adjusted RR=0.94, 95% CI: 0.90, 0.99 for 100–199 mg/day and RR=0.90, 95% CI: 0.85, 0.94 for 200–399 mg/day compared with those consuming <50 mg/day). Individuals who drank more than 1 can/week of artificially sweetened (but not sugar-sweetened) soft drink (cola and other) had a 8% increased risk (95% CI: 1.01–1.16). Neither milk nor tea had a significant effect on mortality after multivariable adjustment. Conclusions Moderate caffeine consumption appeared beneficial in risking risk of death. Attenuation in the observed associations between mortality and intake of tea and milk with adjustment for potential confounders suggests that such consumption identifies those with other mortality-associated lifestyle and health risks. The increased death risk with consumption of artificially sweetened, but not sugar-sweetened, soft drinks suggests an effect of the sweetener rather than other components of the soft drinks, although residual confounding remains a possibility. PMID:17275898

Early school attainment in late-preterm infants.

PubMed

Peacock, Philip J; Henderson, John; Odd, David; Emond, Alan

2012-02-01

To investigate whether infants born late-preterm have poorer school attainment compared to those born at term. This study used data from the Avon Longitudinal Study of Parents and Children. Key stage one (KS1) school assessment results were obtained from local education authorities. Logistic regression models were used to investigate the effect of gestation, that is, late-preterm (32-36 weeks) versus term (37-41 weeks), on success in KS1 teacher assessments. Regression models were adjusted for potential confounders, including maternal education and markers of socioeconomic status. There were 12 089 term infants and 734 late-preterm infants. 71% of late-preterm children were successful in KS1 assessments compared to 79% of those born at term (OR 0.64 (95% CI 0.53 to 0.78); p<0.001). This difference persisted on adjusting for potential confounders (OR 0.74 (95% CI 0.59 to 0.92); p=0.007). Children born late-preterm are less likely to be successful in early school assessments than those born at term. This group of vulnerable children warrants closer surveillance for early identification of potential educational failure.

Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality

PubMed Central

Perin, Jamie; Walker, Neff

2015-01-01

Background Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. Objectives Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. Design We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18–23 months, 24–35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta-analysis with random survey effects. Results We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth intervals less than 18 months, standard regression adjustment for confounding factors estimated a risk ratio for neonatal mortality of 2.28 (95% confidence interval: 2.18–2.37). This same effect estimated within mother is 1.57 (95% confidence interval: 1.52–1.63), a decline of almost one-third in the effect on neonatal mortality. Conclusions Neonatal, infant, and child mortality are strongly and significantly related to preceding birth interval, where births within a short interval of time after the previous birth have increased mortality. Previous analyses have demonstrated this relationship on average across all births; however, women who have short spaces between births are different from women with long spaces. Among women 35 years and older where a comparison of birth spaces within mother is possible, we find a much reduced although still significant effect of short birth spaces on child mortality. PMID:26562139

Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality.

PubMed

Perin, Jamie; Walker, Neff

2015-01-01

Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18-23 months, 24-35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta-analysis with random survey effects. We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth intervals less than 18 months, standard regression adjustment for confounding factors estimated a risk ratio for neonatal mortality of 2.28 (95% confidence interval: 2.18-2.37). This same effect estimated within mother is 1.57 (95% confidence interval: 1.52-1.63), a decline of almost one-third in the effect on neonatal mortality. Neonatal, infant, and child mortality are strongly and significantly related to preceding birth interval, where births within a short interval of time after the previous birth have increased mortality. Previous analyses have demonstrated this relationship on average across all births; however, women who have short spaces between births are different from women with long spaces. Among women 35 years and older where a comparison of birth spaces within mother is possible, we find a much reduced although still significant effect of short birth spaces on child mortality.

Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

PubMed

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

2017-08-17

To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

Fiber typing in aging muscle.

PubMed

Purves-Smith, Fennigje M; Sgarioto, Nicolas; Hepple, Russell T

2014-04-01

It is accepted widely that fast-twitch muscle fibers are preferentially impacted in aging muscle, yet we hypothesize that this is not valid when aging muscle atrophy becomes severe. In this review, we summarize the evidence of fiber type-specific effect in aging muscle and the potential confounding roles of fibers coexpressing multiple myosin heavy-chain isoforms and their histochemical identification.

Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake

USDA-ARS?s Scientific Manuscript database

The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric ...

Dorsal Stream Deficits Suggest Hidden Dyslexia among Deaf Poor Readers: Correlated Evidence from Reduced Perceptual Speed and Elevated Coherent Motion Detection Thresholds

ERIC Educational Resources Information Center

Samar, V.J.; Parasnis, I.

2005-01-01

Prelingual deafness and developmental dyslexia have confounding developmental effects on reading acquisition. Therefore, standard reading assessment methods for diagnosing dyslexia in hearing people are ineffective for use with deaf people. Recently, Samar, Parasnis, and Berent (2002) reported visual evoked potential evidence that deaf poor…

Modeling Gene-Environment Interactions With Quasi-Natural Experiments.

PubMed

Schmitz, Lauren; Conley, Dalton

2017-02-01

This overview develops new empirical models that can effectively document Gene × Environment (G×E) interactions in observational data. Current G×E studies are often unable to support causal inference because they use endogenous measures of the environment or fail to adequately address the nonrandom distribution of genes across environments, confounding estimates. Comprehensive measures of genetic variation are incorporated into quasi-natural experimental designs to exploit exogenous environmental shocks or isolate variation in environmental exposure to avoid potential confounders. In addition, we offer insights from population genetics that improve upon extant approaches to address problems from population stratification. Together, these tools offer a powerful way forward for G×E research on the origin and development of social inequality across the life course. © 2015 Wiley Periodicals, Inc.

Theoretical Basis of the Test-Negative Study Design for Assessment of Influenza Vaccine Effectiveness.

PubMed

Sullivan, Sheena G; Tchetgen Tchetgen, Eric J; Cowling, Benjamin J

2016-09-01

Influenza viruses undergo frequent antigenic changes. As a result, the viruses circulating change within and between seasons, and the composition of the influenza vaccine is updated annually. Thus, estimation of the vaccine's effectiveness is not constant across seasons. In order to provide annual estimates of the influenza vaccine's effectiveness, health departments have increasingly adopted the "test-negative design," using enhanced data from routine surveillance systems. In this design, patients presenting to participating general practitioners with influenza-like illness are swabbed for laboratory testing; those testing positive for influenza virus are defined as cases, and those testing negative form the comparison group. Data on patients' vaccination histories and confounder profiles are also collected. Vaccine effectiveness is estimated from the odds ratio comparing the odds of testing positive for influenza among vaccinated patients and unvaccinated patients, adjusting for confounders. The test-negative design is purported to reduce bias associated with confounding by health-care-seeking behavior and misclassification of cases. In this paper, we use directed acyclic graphs to characterize potential biases in studies of influenza vaccine effectiveness using the test-negative design. We show how studies using this design can avoid or minimize bias and where bias may be introduced with particular study design variations. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Generalizability of dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk

USDA-ARS?s Scientific Manuscript database

Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome this limitation. To examine confounding by dietary pattern as well as ...

Homophily and Contagion Are Generically Confounded in Observational Social Network Studies

PubMed Central

Shalizi, Cosma Rohilla; Thomas, Andrew C.

2012-01-01

The authors consider processes on social networks that can potentially involve three factors: homophily, or the formation of social ties due to matching individual traits; social contagion, also known as social influence; and the causal effect of an individual’s covariates on his or her behavior or other measurable responses. The authors show that generically, all of these are confounded with each other. Distinguishing them from one another requires strong assumptions on the parametrization of the social process or on the adequacy of the covariates used (or both). In particular the authors demonstrate, with simple examples, that asymmetries in regression coefficients cannot identify causal effects and that very simple models of imitation (a form of social contagion) can produce substantial correlations between an individual’s enduring traits and his or her choices, even when there is no intrinsic affinity between them. The authors also suggest some possible constructive responses to these results. PMID:22523436

Acceptance of homosexuality through education? Investigating the role of education, family background and individual characteristics in the United Kingdom.

PubMed

la Roi, Chaïm; Mandemakers, Jornt J

2018-03-01

Higher educated people tend to be more accepting of homosexuality than lower educated people. This has inspired claims that education leads to a higher acceptance of homosexuality. Alternatively, the association between education and acceptance of homosexuality could be confounded by (un)observed family background and stable individual characteristics. This study investigated the association between education and acceptance of homosexuality and the role of potential confounders in a unique longitudinal sample of British siblings. Multilevel and fixed effects analyses show that both perspectives apply. A large part of the association between education and acceptance of homosexuality could be attributed to family background and observed individual characteristics (one third), as well as unobserved individual characteristics (an additional third), but the positive association remains. Findings are discussed in light of existing explanations regarding the effect of education on the acceptance of homosexuality. Copyright © 2017 Elsevier Inc. All rights reserved.

Invited Commentary: Beware the Test-Negative Design.

PubMed

Westreich, Daniel; Hudgens, Michael G

2016-09-01

In this issue of the Journal, Sullivan et al. (Am J Epidemiol. 2016;184(5):345-353) carefully examine the theoretical justification for use of the test-negative design, a common observational study design, in assessing the effectiveness of influenza vaccination. Using modern causal inference methods (in particular, directed acyclic graphs), they describe different threats to the validity of inferences drawn about the effect of vaccination from test-negative design studies. These threats include confounding, selection bias, and measurement error in either the exposure or the outcome. While confounding and measurement error are common in observational studies, the potential for selection bias inherent in the test-negative design brings into question the validity of inferences drawn from such studies. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mediation Analysis: A Practitioner's Guide.

PubMed

VanderWeele, Tyler J

2016-01-01

This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

Potential sources of bias in the use of Escherichia coli to measure waterborne diarrhoea risk in low-income settings.

PubMed

Ercumen, Ayse; Arnold, Benjamin F; Naser, Abu Mohd; Unicomb, Leanne; Colford, John M; Luby, Stephen P

2017-01-01

Escherichia coli is the standard water quality indicator for diarrhoea risk. Yet, the association between E. coli and diarrhoea is inconsistent across studies without a systematic assessment of methodological differences behind this variation. Most studies measure water quality cross-sectionally with diarrhoea, risking exposure misclassification and reverse causation. Studies use different recall windows for self-reported diarrhoea; longer periods increase potential outcome misclassification through misrecall. Control of confounding is inconsistent across studies. Additionally, diarrhoea measured in unblinded intervention trials can present courtesy bias. We utilised measurements from a randomised trial of water interventions in Bangladesh to assess how these factors affect the E. coli-diarrhoea association. We compared cross-sectional versus prospective measurements of water quality and diarrhoea, 2-versus 7-day symptom recall periods, estimates with and without controlling for confounding and using measurements from control versus intervention arms of the trial. In the control arm, 2-day diarrhoea prevalence, measured prospectively 1 month after water quality, significantly increased with log 10 E. coli (PR = 1.50, 1.02-2.20). This association weakened when we used 7-day recall (PR = 1.18, 0.88-1.57), cross-sectional measurements of E. coli and diarrhoea (PR = 1.11, 0.79-1.56) or did not control for confounding (PR = 1.20, 0.88-1.62). Including data from intervention arms led to less interpretable associations, potentially due to courtesy bias, effect modification and/or reverse causation. By systematically addressing potential sources of bias, our analysis demonstrates a clear relationship between E. coli in drinking water and diarrhoea, suggesting that the continued use of E. coli as an indicator of waterborne diarrhoea risk is justified. © 2016 John Wiley & Sons Ltd.

Keeping children safe at home: protocol for three matched case–control studies of modifiable risk factors for falls

PubMed Central

Kendrick, Denise; Stewart, Jane; Clacy, Rose; Coffey, Frank; Cooper, Nicola; Coupland, Carol; Hayes, Mike; McColl, Elaine; Reading, Richard; Sutton, Alex; M L Towner, Elizabeth; Craig Watson, Michael

2012-01-01

Background Childhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children. Objectives To estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity. Design Three multicentre case–control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0–4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences. Main outcome measures Falls on stairs, on one level and from furniture. Discussion As the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children. PMID:22628151

Parkinson’s Disease and PD Medications Have Distinct Signatures of the Gut Microbiome

PubMed Central

Hill-Burns, Erin M.; Debelius, Justine W.; Morton, James T.; Wissemann, William T.; Lewis, Matthew R.; Wallen, Zachary D.; Peddada, Shyamal D.; Factor, Stewart A.; Molho, Eric; Zabetian, Cyrus P.; Knight, Rob; Payami, Haydeh

2017-01-01

Background There is mounting evidence for a connection between the gut and Parkinson’s disease (PD). Dysbiosis of gut microbiota could explain several features of PD. Objective To determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. Methods 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. Results Independent microbial signatures were detected for PD (P=4E-5), subjects’ region of residence within the United States (P=3E-3), age (P=0.03), sex (P=1E-3) and dietary fruits/vegetables (P=0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P=4E-4), anticholinergics (P=5E-3), and possibly carbidopa/levodopa (P=0.05). We found significantly altered abundance of Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways including metabolism of plant-derived compounds and xenobiotics degradation. Conclusion PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. PMID:28195358

JIM-13-0560 R1: Propensity scores for confounder adjustment when assessing the effects of medical interventions using non-experimental study designs

PubMed Central

Stürmer, Til; Wyss, Richard; Glynn, Robert J.; Brookhart, M. Alan

2014-01-01

Treatment effects, especially when comparing two or more therapeutic alternatives as in comparative effectiveness research, are likely to be heterogeneous across age, gender, co-morbidities, and co-medications. Propensity scores (PSs), an alternative to multivariable outcome models to control for measured confounding, have specific advantages in the presence of heterogeneous treatment effects. Implementing PSs using matching or weighting allows us to estimate different overall treatment effects in differently defined populations. Heterogeneous treatment effects can also be due to unmeasured confounding concentrated in those treated contrary to prediction. Sensitivity analyses based on PSs can help to assess such unmeasured confounding. PSs should be considered a primary or secondary analytic strategy in non-experimental medical research, including pharmacoepidemiology and non-experimental comparative effectiveness research. PMID:24520806

Recognizing potential barriers to setting and achieving effective rehabilitation goals for patients with persistent pain.

PubMed

Schmidt, Stephen G

2016-07-01

Although the process of goal setting in rehabilitation of individuals with persistent pain is considered a fundamental and requisite skill, it is frequently reported as a challenging element of clinical practice. Factors which may contribute to the complexity of goal setting include the potential for unrecognized shifts in cognitive function, psychological comorbidities, and the social context of both providers and patients. This review aims to describe factors which may confound the process of setting and achieving collaborative rehabilitation goals using a biopsychosocial framework and to provide recommendations to enhance goal setting effectiveness.

Confounder Detection in High-Dimensional Linear Models Using First Moments of Spectral Measures.

PubMed

Liu, Furui; Chan, Laiwan

2018-06-12

In this letter, we study the confounder detection problem in the linear model, where the target variable [Formula: see text] is predicted using its [Formula: see text] potential causes [Formula: see text]. Based on an assumption of a rotation-invariant generating process of the model, recent study shows that the spectral measure induced by the regression coefficient vector with respect to the covariance matrix of [Formula: see text] is close to a uniform measure in purely causal cases, but it differs from a uniform measure characteristically in the presence of a scalar confounder. Analyzing spectral measure patterns could help to detect confounding. In this letter, we propose to use the first moment of the spectral measure for confounder detection. We calculate the first moment of the regression vector-induced spectral measure and compare it with the first moment of a uniform spectral measure, both defined with respect to the covariance matrix of [Formula: see text]. The two moments coincide in nonconfounding cases and differ from each other in the presence of confounding. This statistical causal-confounding asymmetry can be used for confounder detection. Without the need to analyze the spectral measure pattern, our method avoids the difficulty of metric choice and multiple parameter optimization. Experiments on synthetic and real data show the performance of this method.

The link between early onset drinking and early onset alcohol-impaired driving in young males.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2014-05-01

Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

Gender effects in gaming research: a case for regression residuals?

PubMed

Pfister, Roland

2011-10-01

Numerous recent studies have examined the impact of video gaming on various dependent variables, including the players' affective reactions, positive as well as detrimental cognitive effects, and real-world aggression. These target variables are typically analyzed as a function of game characteristics and player attributes-especially gender. However, findings on the uneven distribution of gaming experience between males and females, on the one hand, and the effect of gaming experience on several target variables, on the other hand, point at a possible confound when gaming experiments are analyzed with a standard analysis of variance. This study uses simulated data to exemplify analysis of regression residuals as a potentially beneficial data analysis strategy for such datasets. As the actual impact of gaming experience on each of the various dependent variables differs, the ultimate benefits of analysis of regression residuals entirely depend on the research question, but it offers a powerful statistical approach to video game research whenever gaming experience is a confounding factor.

Eliminating Survivor Bias in Two-stage Instrumental Variable Estimators.

PubMed

Vansteelandt, Stijn; Walter, Stefan; Tchetgen Tchetgen, Eric

2018-07-01

Mendelian randomization studies commonly focus on elderly populations. This makes the instrumental variables analysis of such studies sensitive to survivor bias, a type of selection bias. A particular concern is that the instrumental variable conditions, even when valid for the source population, may be violated for the selective population of individuals who survive the onset of the study. This is potentially very damaging because Mendelian randomization studies are known to be sensitive to bias due to even minor violations of the instrumental variable conditions. Interestingly, the instrumental variable conditions continue to hold within certain risk sets of individuals who are still alive at a given age when the instrument and unmeasured confounders exert additive effects on the exposure, and moreover, the exposure and unmeasured confounders exert additive effects on the hazard of death. In this article, we will exploit this property to derive a two-stage instrumental variable estimator for the effect of exposure on mortality, which is insulated against the above described selection bias under these additivity assumptions.

Why Do White Americans Oppose Race-Targeted Policies? Clarifying the Impact of Symbolic Racism

PubMed Central

Rabinowitz, Joshua L.; Sears, David O.; Sidanius, Jim; Krosnick, Jon A.

2009-01-01

Measures of symbolic racism (SR) have often been used to tap racial prejudice toward Blacks. However, given the wording of questions used for this purpose, some of the apparent effects on attitudes toward policies to help Blacks may instead be due to political conservatism, attitudes toward government, and/or attitudes toward redistributive government policies in general. Using data from national probability sample surveys and an experiment, we explored whether SR has effects even when controlling for these potential confounds and whether its effects are specific to policies involving Blacks. Holding constant conservatism and attitudes toward limited government, SR predicted Whites' opposition to policies designed to help Blacks and more weakly predicted attitudes toward social programs whose beneficiaries were racially ambiguous. An experimental manipulation of policy beneficiaries revealed that SR predicted policy attitudes when Blacks were the beneficiary but not when women were. These findings are consistent with the claim that SR's association with racial policy preferences is not due to these confounds. PMID:20161542

Effects of anesthesia on the cerebral capillary blood flow in young and old mice

NASA Astrophysics Data System (ADS)

Moeini, Mohammad; Tabatabaei, Maryam S.; Bélanger, Samuel; Avti, Pramod; Castonguay, Alexandre; Pouliot, Philippe; Lesage, Frédéric

2015-03-01

Despite recent findings on the possible role of age-related cerebral microvasculature changes in cognition decline, previous studies of capillary blood flow in aging (using animal models) are scarce and limited to anesthetized conditions. Since anesthesia can have different effects in young and old animals, it may introduce a confounding effect in aging studies. The present study aimed to eliminate the potential confound introduced by anesthesia by measuring capillary blood flow parameters in both awake conditions and under isoflurane anesthesia. We used 2-photon laser scanning fluorescence microscopy to measure capillary diameter, red blood cell velocity and flux, hematocrit and capillary volumetric flow in individual capillaries in the barrel cortex of 6- and 24-month old C57Bl/6 mice. It was observed that microvascular properties are significantly affected by anesthesia leading to different trends in capillary blood flow parameters with aging when measured under awake or anesthetized conditions. The findings in this study suggest taking extra care in interpreting aging studies from anesthetized animals.

Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

PubMed

Costa-Nunes, João P; Cline, Brandon H; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W M; Strekalova, Tatyana

2015-01-01

Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.

Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

PubMed Central

Costa-Nunes, João P.; Cline, Brandon H.; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W. M.

2015-01-01

Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. PMID:26064929

Interpreting large-scale experiments on effects of trawling on benthic fauna: an empirical test of the potential effects of spatial confounding in experiments without replicated control and trawled areas.

PubMed

Lindegarth; Valentinsson; Hansson; Ulmestrand

2000-03-15

Disturbances due to trawling and dredging is a serious threat to assemblages of benthic marine animals. We tested hypotheses about effects of trawling on benthic assemblages in a manipulative field experiment, using gear and intensities relevant to future management of trawling in a Swedish fjord. Three trawled and three control sites were sampled at several times before and after trawling was initiated. This paper describes how conclusions about effects of trawling might differ between experiments involving replicate sites and experiments using only one trawled and one control site, as in several recent studies. Analyses of selected taxa showed that abundances of many species changed differently among control sites. Differences in temporal change between pairs of single trawled and control sites were also frequent. Neither the quantitative nor the qualitative nature of differences between treatments could, however, be coherently interpreted among the different combinations of trawled and control sites. This is consistent with results obtained from analyses using all sites, which showed no consistent effects of trawling on any of these taxa. These results provide empirical evidence that spatial confounding may cause serious problems to formal interpretation of experiments, which use only one control and one trawled area. Such potential problems can best be solved by ensuring that the study incorporates more than one control site.

Breast milk and cognitive development—the role of confounders: a systematic review

PubMed Central

Walfisch, Asnat; Sermer, Corey; Cressman, Alex; Koren, Gideon

2013-01-01

Objectives The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ. Design Systematic review of the literature. Setting and participants Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included. Primary and secondary outcome measures Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants’ age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well. Results 84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive—diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%). Conclusions Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously control for all important confounders. Alternatively, study designs using sibling cohorts discordant for breastfeeding may yield more robust conclusions. PMID:23975102

Maternal Smoking during Pregnancy and Children's Cognitive and Physical Development: A Causal Risk Factor?

PubMed Central

Gardener, Hannah; Buka, Stephen L.

2008-01-01

There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959–1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of −85.63 g associated with smoking of ≥20 cigarettes daily during pregnancy (95% confidence interval: −131.91, −39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking. PMID:18653646

The differential effects of tangible rewards and praise on intrinsic motivation: A comparison of cognitive evaluation theory and operant theory.

PubMed

Carton, J S

1996-01-01

Substantial research indicates that tangible rewards, such as money, prizes, and tokens, decrease response rates by undermining intrinsic motivation. In contrast, praise appears to increase response rates by enhancing intrinsic motivation. Based on their interpretation of available evidence, many social-cognitive researchers warn not to use tangible rewards in applied settings and to use praise instead. Furthermore, they suggest that the differential effects of the two types of rewards on intrinsic motivation cannot be explained using principles of operant psychology. Cognitive evaluation theory provides one of the most recent and widely cited social-cognitive explanations for the different effects of the two types of rewards on intrinsic motivation (Deci & Ryan, 1985). However, a review of existing research found little support for the explanations based on this theory and revealed three potential confounding effects: (a) temporal contiguity, (b) the number of reward administrations, and (c) discriminative stimuli associated with reward availability. These three confounding factors provide explanations for the effects of tangible rewards and praise on intrinsic motivation that are consistent with principles of operant psychology.

The differential effects of tangible rewards and praise on intrinsic motivation: A comparison of cognitive evaluation theory and operant theory

PubMed Central

Carton, John S.

1996-01-01

Substantial research indicates that tangible rewards, such as money, prizes, and tokens, decrease response rates by undermining intrinsic motivation. In contrast, praise appears to increase response rates by enhancing intrinsic motivation. Based on their interpretation of available evidence, many social-cognitive researchers warn not to use tangible rewards in applied settings and to use praise instead. Furthermore, they suggest that the differential effects of the two types of rewards on intrinsic motivation cannot be explained using principles of operant psychology. Cognitive evaluation theory provides one of the most recent and widely cited social-cognitive explanations for the different effects of the two types of rewards on intrinsic motivation (Deci & Ryan, 1985). However, a review of existing research found little support for the explanations based on this theory and revealed three potential confounding effects: (a) temporal contiguity, (b) the number of reward administrations, and (c) discriminative stimuli associated with reward availability. These three confounding factors provide explanations for the effects of tangible rewards and praise on intrinsic motivation that are consistent with principles of operant psychology. PMID:22478261

A framework for a critical assessment of the quality of epidemiological studies of driver health and accident risk.

PubMed

Elvik, Rune

2011-11-01

A large number of studies have tried to assess how various aspects of driver health influence driver involvement in accidents. The objective of this paper is to provide a framework for a critical assessment of the quality these studies from a methodological point of view. Examples are given of how various sources of bias and confounding can produce study findings that are highly misleading. Ten potential sources of error and bias in epidemiological studies of the contribution of driver health impairments to road accidents are discussed: (1) Poor description of the medical conditions whose effects are studied (measurement error). (2) Inadequate control for the effects of exposure on accident rate. (3) Sampling endogeneity with respect to assessment for fitness to drive (outcome-based sampling; self-selection bias). (4) Combined exposure to several risk factors. (5) Poor control for potentially confounding factors. (6) Failure to specify potentially moderating factors (interaction effects). (7) Failure to consider a severity gradient with respect to the effect of health impairments. (8) Failure to specify the compliance of drivers with medical treatments or treatment effectiveness. (9) No data on the population prevalence of various health conditions. (10) The use of multiple study approaches and methods making the comparison and synthesis of findings difficult. Examples are given of how all these items may influence the findings of a single study or make synthesising findings from multiple studies difficult. A checklist for assessing study quality is provided. Copyright © 2011 Elsevier Ltd. All rights reserved.

The assessment of cortisol in human hair: associations with sociodemographic variables and potential confounders.

PubMed

Dettenborn, L; Tietze, A; Kirschbaum, C; Stalder, T

2012-11-01

To inform the future use of hair cortisol measurement, we have investigated influences of potential confounding variables (natural hair colour, frequency of hair washes, age, sex, oral contraceptive (OC) use and smoking status) on hair cortisol levels. The main study sample comprised 360 participants (172 women) covering a wide range of ages (1-91 years; mean = 25.95). In addition, to more closely examine influences of natural hair colour and young age on hair cortisol levels, two additional samples comprising 69 participants with natural blond or dark brown hair (hair colour sample) as well as 28 young children and 34 adults (young age sample) were recruited. Results revealed a lack of an effect for natural hair colour, OC use, and smoking status on hair cortisol levels (all p's >0.10). No influence of frequency of hair washes was seen for proximal hair segments (p = 0.335) but for the third hair segment indicating lower cortisol content (p = 0.008). We found elevated hair cortisol levels in young children and older adults (p < 0.001). Finally, men showed higher hair cortisol levels than women (p = 0.002). The present data indicate that hair cortisol measurement provides a useful tool in stress-related psychobiological research when applied with the consideration of possible confounders including age and sex.

Validation sampling can reduce bias in health care database studies: an illustration using influenza vaccination effectiveness.

PubMed

Nelson, Jennifer Clark; Marsh, Tracey; Lumley, Thomas; Larson, Eric B; Jackson, Lisa A; Jackson, Michael L

2013-08-01

Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased owing to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias. We applied two such methods, namely imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method's ability to reduce bias using the control time period before influenza circulation. Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not use the validation sample confounders. Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from health care database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which the data can be imputed or reweighted using the additional validation sample information. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation sampling can reduce bias in healthcare database studies: an illustration using influenza vaccination effectiveness

PubMed Central

Nelson, Jennifer C.; Marsh, Tracey; Lumley, Thomas; Larson, Eric B.; Jackson, Lisa A.; Jackson, Michael

2014-01-01

Objective Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased due to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias. Study Design and Setting We applied two such methods, imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method’s ability to reduce bias using the control time period prior to influenza circulation. Results Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not utilize the validation sample confounders. Conclusion Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from healthcare database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which data can be imputed or reweighted using the additional validation sample information. PMID:23849144

The Discriminatory Ability of the Fibromyalgia Rapid Screening Tool (FiRST): An International Study in Spain and Four Latin American Countries.

PubMed

Collado, Antonio; Torres, Xavier; Messina, Osvaldo D; Vidal, Luis F; Clark, Patricia; Ríos, Carlos; Solé, Emília; Arias, Anna; Perrot, Serge; Salomon, Patricia A

2016-05-01

To assess the transcultural equivalency of the Spanish version of the Fibromyalgia Rapid Screening Tool (FiRST) and its discriminatory ability in different Latin American samples. Validation study. Departments of Rheumatology in general hospitals and private centers; fibromyalgia unit in a university hospital. 350 chronic pain patients from Spain, Argentina, Mexico, Peru, and Ecuador. The cultural relevance of the Spanish version of the FiRST was evaluated. The ability of the FiRST as a screening tool for fibromyalgia was assessed by logistic regression analysis. To determine the degree to which potential confounders, such as differences in demographics, pain, affective distress, catastrophizing, and disability, might affect the discriminatory ability, the tool was reassessed by hierarchical multivariate logistic regression. Slightly different versions of the FiRST were recommended for use in each Latin American subsample. The FiRST showed acceptable criterion validity and was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, low specificities were observed in samples from Spain and Mexico. The Spanish version of the FiRST may be used as a screening tool for fibromyalgia in several Latin American subsamples, even in those patients with high scores on potential confounders. In Spain and Mexico, the low specificity of the FiRST suggests, however, that it would be best used to support a suspected diagnosis of fibromyalgia, rather than to exclude the diagnosis. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Increased popliteal circumferential wall tension induced by orthostatic body posture is associated with local atherosclerotic plaques.

PubMed

Gemignani, Tiago; Azevedo, Renata C; Higa, Celina M; Coelho, Otávio R; Matos-Souza, José R; Nadruz, Wilson

2012-09-01

Lower limb arteries are exposed to higher hemodynamic burden in erectile posture. This study evaluated the effects of body posture on popliteal, carotid and brachial circumferential wall tension (CWT) and investigated the relationship between local CWT and atherosclerotic plaques in subjects with cardiovascular risk factors. Two hundred and three subjects (118 women and 85 men) with cardiovascular risk factors (smoking, hypertension or diabetes mellitus) underwent clinical and laboratory analysis and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Arteries were evaluated by ultrasound analysis, while CWT was calculated according to Laplace's law. Among the enrolled participants, 47%, 29% and none presented popliteal, carotid and brachial plaques, respectively. Carotid CWT measurements were not associated with local plaques after adjustment for potential confounders. Conversely, general linear model and logistic regression analyses adjusted for potential confounders demonstrated that peak orthostatic CWT was the only local hemodynamic parameter showing significant relationship with popliteal plaques in the whole sample. In gender-specific analyses, although positively correlated with popliteal plaques in both genders, local peak orthostatic CWT exhibited an independent association with popliteal plaques after adjustment for potential confounders only in women. Popliteal CWT measured in orthostatic posture, rather than in supine position, is associated with popliteal atherosclerotic plaques, particularly in women. These findings suggest that erectile posture might play a role in the atherogenesis of leg arteries by modifying local hemodynamic forces and that there may be gender differences in this regard. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Inhibitory Control in Siblings Discordant for Exposure to Maternal Smoking during Pregnancy

ERIC Educational Resources Information Center

Micalizzi, Lauren; Marceau, Kristine; Brick, Leslie A.; Palmer, Rohan H.; Todorov, Alexandre A.; Heath, Andrew C.; Evans, Allison; Knopik, Valerie S.

2018-01-01

Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e., genetic and environmental) confounds, preclude concluding causal effects…

Perceived fairness of pay among people with and without disabilities: a propensity score matched analysis of working Australians.

PubMed

Milner, Allison; Aitken, Zoe; Krnjacki, Lauren; Bentley, Rebecca; Blakely, Tony; LaMontagne, Anthony D; Kavanagh, Anne M

2015-09-01

Equity and fairness at work are associated with a range of organizational and health outcomes. Past research suggests that workers with disabilities experience inequity in the workplace. It is difficult to conclude whether the presence of disability is the reason for perceived unfair treatment due to the possible confounding of effect estimates by other demographic or socioeconomic factors. The data source was the Household, Income, and Labor Dynamics in Australia (HILDA) survey (2001-2012). Propensity for disability was calculated from logistic models including gender, age, education, country of birth, and father's occupational skill level as predictors. We then used nearest neighbor (on propensity score) matched analysis to match workers with disabilities to workers without disability. Results suggest that disability is independently associated with lower fairness of pay after controlling for confounding factors in the propensity score matched analysis; although results do suggest less than half a standard deviation difference, indicating small effects. Similar results were apparent in standard multivariable regression models and alternative propensity score analyses (stratification, covariate adjustment using the propensity score, and inverse probability of treatment weighting). Whilst neither multivariable regression nor propensity scores adjust for unmeasured confounding, and there remains the potential for other biases, similar results for the two methodological approaches to confounder adjustment provide some confidence of an independent association of disability with perceived unfairness of pay. Based on this, we suggest that the disparity in the perceived fairness of pay between people with and without disabilities may be explained by worse treatment of people with disabilities in the workplace.

Effect of breast feeding on intelligence in children: prospective study, sibling pairs analysis, and meta-analysis.

PubMed

Der, Geoff; Batty, G David; Deary, Ian J

2006-11-04

To assess the importance of maternal intelligence, and the effect of controlling for it and other important confounders, in the link between breast feeding and children's intelligence. Examination of the effect of breast feeding on cognitive ability and the impact of a range of potential confounders, in particular maternal IQ, within a national database. Additional analyses compared pairs of siblings from the sample who were and were not breast fed. The results are considered in the context of other studies that have also controlled for parental intelligence via meta-analysis. 1979 US national longitudinal survey of youth. Data on 5475 children, the offspring of 3161 mothers in the longitudinal survey. IQ in children measured by Peabody individual achievement test. The mother's IQ was more highly predictive of breastfeeding status than were her race, education, age, poverty status, smoking, the home environment, or the child's birth weight or birth order. One standard deviation advantage in maternal IQ more than doubled the odds of breast feeding. Before adjustment, breast feeding was associated with an increase of around 4 points in mental ability. Adjustment for maternal intelligence accounted for most of this effect. When fully adjusted for a range of relevant confounders, the effect was small (0.52) and non-significant (95% confidence interval -0.19 to 1.23). The results of the sibling comparisons and meta-analysis corroborated these findings. Breast feeding has little or no effect on intelligence in children. While breast feeding has many advantages for the child and mother, enhancement of the child's intelligence is unlikely to be among them.

The relationship between hand hygiene and health care-associated infection: it’s complicated

PubMed Central

McLaws, Mary-Louise

2015-01-01

The reasoning that improved hand hygiene compliance contributes to the prevention of health care-associated infections is widely accepted. It is also accepted that high hand hygiene alone cannot impact formidable risk factors, such as older age, immunosuppression, admission to the intensive care unit, longer length of stay, and indwelling devices. When hand hygiene interventions are concurrently undertaken with other routine or special preventive strategies, there is a potential for these concurrent strategies to confound the effect of the hand hygiene program. The result may be an overestimation of the hand hygiene intervention unless the design of the intervention or analysis controls the effect of the potential confounders. Other epidemiologic principles that may also impact the result of a hand hygiene program include failure to consider measurement error of the content of the hand hygiene program and the measurement error of compliance. Some epidemiological errors in hand hygiene programs aimed at reducing health care-associated infections are inherent and not easily controlled. Nevertheless, the inadvertent omission by authors to report these common epidemiological errors, including concurrent infection prevention strategies, suggests to readers that the effect of hand hygiene is greater than the sum of all infection prevention strategies. Worse still, this omission does not assist evidence-based practice. PMID:25678805

Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa).

PubMed

Zuccolo, Luisa; DeRoo, Lisa A; Wills, Andrew K; Davey Smith, George; Suren, Pål; Roth, Christine; Stoltenberg, Camilla; Magnus, Per

2016-12-23

Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

Multigenerational effects of parental prenatal exposure to famine on adult offspring cognitive function

PubMed Central

Li, Jie; Na, Lixin; Ma, Hao; Zhang, Zhe; Li, Tianjiao; Lin, Liqun; Li, Qiang; Sun, Changhao; Li, Ying

2015-01-01

The effects of prenatal nutrition on adult cognitive function have been reported for one generation. However, human evidence for multigenerational effects is lacking. We examined whether prenatal exposure to the Chinese famine of 1959–61 affects adult cognitive function in two consecutive generations. In this retrospective family cohort study, we investigated 1062 families consisting of 2124 parents and 1215 offspring. We assessed parental and offspring cognitive performance by means of a comprehensive test battery. Generalized linear regression model analysis in the parental generation showed that prenatal exposure to famine was associated with a 8.1 (95% CI 5.8 to 10.4) second increase in trail making test part A, a 7.0 (1.5 to 12.5) second increase in trail making test part B, and a 5.5 (−7.3 to −3.7) score decrease in the Stroop color-word test in adulthood, after adjustment for potential confounders. In the offspring generation, linear mixed model analysis found no significant association between parental prenatal exposure to famine and offspring cognitive function in adulthood after adjustment for potential confounders. In conclusion, prenatal exposure to severe malnutrition is negatively associated with visual- motor skill, mental flexibility, and selective attention in adulthood. However, these associations are limited to only one generation. PMID:26333696

A Male Advantage for Spatial and Object but Not Verbal Working Memory Using the N-Back Task

ERIC Educational Resources Information Center

Lejbak, Lisa; Crossley, Margaret; Vrbancic, Mirna

2011-01-01

Sex-related differences have been reported for performance and neural substrates on some working memory measures that carry a high cognitive load, including the popular n-back neuroimaging paradigm. Despite some evidence of a sex effect on the task, the influence of sex on performance represents a potential confound in neuroimaging research. The…

Effects of Cognitive Load on Trust

DTIC Science & Technology

2013-10-01

that may be affected by load  Build a parsing tool to extract relevant features  Statistical analysis of results (by load components) Achieved...for a business application. Participants assessed potential job candidates and reviewed the applicants’ virtual resume which included standard...substantially different from each other that would make any confounding problems or other issues. Some statistics of the Australian data collection are

Moral Emotion Attributions and Personality Traits as Long-Term Predictors of Antisocial Conduct in Early Adulthood: Findings from a 20-Year Longitudinal Study

ERIC Educational Resources Information Center

Krettenauer, Tobias; Asendorpf, Jens B.; Nunner-Winkler, Gertrud

2013-01-01

The study investigated long-term relations between moral emotion attributions in childhood and adolescence and antisocial conduct in early adulthood while taking into account potentially confounding personality factors. Specifically, onset of prediction, unique and indirect effects of moral emotion attributions were examined. In a longitudinal…

Environmental confounding in gene-environment interaction studies.

PubMed

Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

2013-07-01

We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

Refining adverse drug reaction signals by incorporating interaction variables identified using emergent pattern mining.

PubMed

Reps, Jenna M; Aickelin, Uwe; Hubbard, Richard B

2016-02-01

To develop a framework for identifying and incorporating candidate confounding interaction terms into a regularised cox regression analysis to refine adverse drug reaction signals obtained via longitudinal observational data. We considered six drug families that are commonly associated with myocardial infarction in observational healthcare data, but where the causal relationship ground truth is known (adverse drug reaction or not). We applied emergent pattern mining to find itemsets of drugs and medical events that are associated with the development of myocardial infarction. These are the candidate confounding interaction terms. We then implemented a cohort study design using regularised cox regression that incorporated and accounted for the candidate confounding interaction terms. The methodology was able to account for signals generated due to confounding and a cox regression with elastic net regularisation correctly ranking the drug families known to be true adverse drug reactions above those that are not. This was not the case without the inclusion of the candidate confounding interaction terms, where confounding leads to a non-adverse drug reaction being ranked highest. The methodology is efficient, can identify high-order confounding interactions and does not require expert input to specify outcome specific confounders, so it can be applied for any outcome of interest to quickly refine its signals. The proposed method shows excellent potential to overcome some forms of confounding and therefore reduce the false positive rate for signal analysis using longitudinal data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perceived Discrimination among African American Adolescents and Allostatic Load: A Longitudinal Analysis with Buffering Effects

PubMed Central

Brody, Gene H.; Lei, Man-Kit; Chae, David H.; Yu, Tianyi; Kogan, Steven M.; Beach, Steven R. H.

2013-01-01

This study was designed to examine the prospective relations of perceived racial discrimination with allostatic load (AL), along with a possible buffer of the association. A sample of 331 African Americans in the rural South provided assessments of perceived discrimination from ages 16 to 18 years. When youths were 18, caregivers reported parental emotional support, and youths assessed peer emotional support. AL and potential confounder variables were assessed when youths were 20. Latent Growth Mixture Modeling identified two perceived discrimination classes: high and stable and low and increasing. Adolescents in the high and stable class evinced heightened AL even with confounder variables controlled. The racial discrimination to AL link was not significant for young adults who received high emotional support. PMID:24673162

A causal examination of the effects of confounding factors on multimetric indices

USGS Publications Warehouse

Schoolmaster, Donald R.; Grace, James B.; Schweiger, E. William; Mitchell, Brian R.; Guntenspergen, Glenn R.

2013-01-01

The development of multimetric indices (MMIs) as a means of providing integrative measures of ecosystem condition is becoming widespread. An increasingly recognized problem for the interpretability of MMIs is controlling for the potentially confounding influences of environmental covariates. Most common approaches to handling covariates are based on simple notions of statistical control, leaving the causal implications of covariates and their adjustment unstated. In this paper, we use graphical models to examine some of the potential impacts of environmental covariates on the observed signals between human disturbance and potential response metrics. Using simulations based on various causal networks, we show how environmental covariates can both obscure and exaggerate the effects of human disturbance on individual metrics. We then examine from a causal interpretation standpoint the common practice of adjusting ecological metrics for environmental influences using only the set of sites deemed to be in reference condition. We present and examine the performance of an alternative approach to metric adjustment that uses the whole set of sites and models both environmental and human disturbance effects simultaneously. The findings from our analyses indicate that failing to model and adjust metrics can result in a systematic bias towards those metrics in which environmental covariates function to artificially strengthen the metric–disturbance relationship resulting in MMIs that do not accurately measure impacts of human disturbance. We also find that a “whole-set modeling approach” requires fewer assumptions and is more efficient with the given information than the more commonly applied “reference-set” approach.

Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection

PubMed Central

Cheng, Shao-Bin; Lin, Ping-Ting; Liu, Hsiao-Tien; Peng, Yi-Shan; Huang, Shih-Chien

2016-01-01

Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5′-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β = −2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β = −162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov. PMID:27051670

Interviewer effects on non-response propensity in longitudinal surveys: a multilevel modelling approach

PubMed Central

Vassallo, Rebecca; Durrant, Gabriele B; Smith, Peter W F; Goldstein, Harvey

2015-01-01

The paper investigates two different multilevel approaches, the multilevel cross-classified and the multiple-membership models, for the analysis of interviewer effects on wave non-response in longitudinal surveys. The models proposed incorporate both interviewer and area effects to account for the non-hierarchical structure, the influence of potentially more than one interviewer across waves and possible confounding of area and interviewer effects arising from the non-random allocation of interviewers across areas. The methods are compared by using a data set: the UK Family and Children Survey. PMID:25598587

Concurrent and Sustained Cumulative Effects of Adolescent Marijuana Use on Subclinical Psychotic Symptoms.

PubMed

Bechtold, Jordan; Hipwell, Alison; Lewis, David A; Loeber, Rolf; Pardini, Dustin

2016-08-01

Adolescents who regularly use marijuana may be at heightened risk of developing subclinical and clinical psychotic symptoms. However, this association could be explained by reverse causation or other factors. To address these limitations, the current study examined whether adolescents who engage in regular marijuana use exhibit a systematic increase in subclinical psychotic symptoms that persists during periods of sustained abstinence. The sample comprised 1,009 boys who were recruited in 1st and 7th grades. Self-reported frequency of marijuana use, subclinical psychotic symptoms, and several time-varying confounds (e.g., other substance use, internalizing/externalizing problems) were recorded annually from age 13 to 18. Fixed-effects (within-individual change) models examined whether adolescents exhibited an increase in their subclinical psychotic symptoms as a function of their recent and/or cumulative history of regular marijuana use and whether these effects were sustained following abstinence. Models controlled for all time-stable factors (default) and several time-varying covariates as potential confounds. For each year adolescent boys engaged in regular marijuana use, their expected level of subsequent subclinical psychotic symptoms rose by 21% and their expected odds of experiencing subsequent subclinical paranoia or hallucinations rose by 133% and 92%, respectively. The effect of prior regular marijuana use on subsequent subclinical psychotic symptoms persisted even when adolescents stopped using marijuana for a year. These effects were after controlling for all time-stable and several time-varying confounds. No support was found for reverse causation. These results suggest that regular marijuana use may significantly increase the risk that an adolescent will experience persistent subclinical psychotic symptoms.

Comparison of Statistical Approaches Dealing with Time-dependent Confounding in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W.; Tremlett, Helen

2017-01-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models (MSCMs) are frequently used to deal with such confounding. To avoid some of the problems of fitting MSCM, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as MSCM in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995 – 2008). PMID:27659168

Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies.

PubMed

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W; Tremlett, Helen

2018-06-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as marginal structural Cox model in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995-2008).

On the definition of a confounder

PubMed Central

VanderWeele, Tyler J.; Shpitser, Ilya

2014-01-01

Summary The causal inference literature has provided a clear formal definition of confounding expressed in terms of counterfactual independence. The causal inference literature has not, however, produced a clear formal definition of a confounder, as it has given priority to the concept of confounding over that of a confounder. We consider a number of candidate definitions arising from various more informal statements made in the literature. We consider the properties satisfied by each candidate definition, principally focusing on (i) whether under the candidate definition control for all “confounders” suffices to control for “confounding” and (ii) whether each confounder in some context helps eliminate or reduce confounding bias. Several of the candidate definitions do not have these two properties. Only one candidate definition of those considered satisfies both properties. We propose that a “confounder” be defined as a pre-exposure covariate C for which there exists a set of other covariates X such that effect of the exposure on the outcome is unconfounded conditional on (X, C) but such that for no proper subset of (X, C) is the effect of the exposure on the outcome unconfounded given the subset. A variable that helps reduce bias but not eliminate bias we propose referring to as a “surrogate confounder.” PMID:25544784

Major Depressive Disorder and Impulsive Reactivity to Emotion: Toward a Dual Process View of Depression

PubMed Central

Carver, Charles S.; Johnson, Sheri L.; Joormann, Jutta

2012-01-01

Objective Dual process theories of behavior have been used to suggest that vulnerability to depression involves elevated reactivity to emotions. This study tests that idea, examining self-reported reactivity. Design Comparison between persons with at least one lifetime episode of major depressive disorder (lifetime MDD) and those without this diagnosis, controlling for symptoms of alcohol use (a potential externalizing confound) and current symptoms of depression (a potential state-dependent confound). Methods Undergraduates (N = 120) completed a clinical interview to diagnose lifetime MDD and a series of self-reports bearing on diverse aspects of self-control, including reactivity to emotion. Thirty-four were diagnosed with lifetime MDD; 86 did not meet criteria for MDD. The groups were then compared on three factors underlying the scales assessing self-control. Results The MDD group had higher scores than controls on the two factors that reflect impulsive reactivity to diverse emotions, including emotions that are positive in valence. These effects were not explained by associations with either externalizing symptoms or current depressive symptoms. Conclusions Reflexive reactivity to emotions characterizes depression, in addition to some externalizing problems, and it may deserve study as a potential transdiagnostic feature. PMID:23865405

Structural confounding of area-level deprivation and segreation: an empirical example

EPA Science Inventory

The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

Statistical primer: propensity score matching and its alternatives.

PubMed

Benedetto, Umberto; Head, Stuart J; Angelini, Gianni D; Blackstone, Eugene H

2018-06-01

Propensity score (PS) methods offer certain advantages over more traditional regression methods to control for confounding by indication in observational studies. Although multivariable regression models adjust for confounders by modelling the relationship between covariates and outcome, the PS methods estimate the treatment effect by modelling the relationship between confounders and treatment assignment. Therefore, methods based on the PS are not limited by the number of events, and their use may be warranted when the number of confounders is large, or the number of outcomes is small. The PS is the probability for a subject to receive a treatment conditional on a set of baseline characteristics (confounders). The PS is commonly estimated using logistic regression, and it is used to match patients with similar distribution of confounders so that difference in outcomes gives unbiased estimate of treatment effect. This review summarizes basic concepts of the PS matching and provides guidance in implementing matching and other methods based on the PS, such as stratification, weighting and covariate adjustment.

Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome.

PubMed

Hill-Burns, Erin M; Debelius, Justine W; Morton, James T; Wissemann, William T; Lewis, Matthew R; Wallen, Zachary D; Peddada, Shyamal D; Factor, Stewart A; Molho, Eric; Zabetian, Cyrus P; Knight, Rob; Payami, Haydeh

2017-05-01

There is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD. The objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. A total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. Independent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation. PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia.

PubMed

Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

2016-01-01

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent "time effects" in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered.

An introduction to instrumental variables analysis: part 1.

PubMed

Bennett, Derrick A

2010-01-01

There are several examples in the medical literature where the associations of treatment effects predicted by observational studies have been refuted by evidence from subsequent large-scale randomised trials. This is because of the fact that non-experimental studies are subject to confounding - and confounding cannot be entirely eliminated even if all known confounders have been measured in the study as there may be unknown confounders. The aim of this 2-part methodological primer is to introduce an emerging methodology for estimating treatment effects using observational data in the absence of good randomised evidence known as the method of instrumental variables. Copyright © 2010 S. Karger AG, Basel.

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding

PubMed Central

Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James

2014-01-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding.

PubMed

MacKenzie, Todd A; Tosteson, Tor D; Morden, Nancy E; Stukel, Therese A; O'Malley, A James

2014-06-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival.

What Have the Difference Scores Not Been Telling Us? A Critique of the Use of Self-Ideal Discrepancy in the Assessment of Body Image and Evaluation of an Alternative Data-Analytic Framework

ERIC Educational Resources Information Center

Cafri, Guy; van den Berg, Patricia; Brannick, Michael T.

2010-01-01

Difference scores are often used as a means of assessing body image satisfaction using silhouette scales. Unfortunately, difference scores suffer from numerous potential methodological problems, including reduced reliability, ambiguity, confounded effects, untested constraints, and dimensional reduction. In this article, the methodological…

Child maltreatment and educational attainment in young adulthood: results from the Ontario Child Health Study.

PubMed

Tanaka, Masako; Georgiades, Katholiki; Boyle, Michael H; MacMillan, Harriet L

2015-01-01

There is increasing evidence for the adverse effects of child maltreatment on academic performance; however, most of these studies used selective samples and did not account for potential confounding or mediating factors. We examined the relationship between child physical abuse (PA; severe and non-severe) and sexual abuse (SA) and educational attainment (years of education, failure to graduate from high school) with a Canadian community sample. We used data from the Ontario Child Health Study (N = 1,893), a province-wide longitudinal survey. Potential confounding variables (family socio-demographic and parental capacity) and child-level characteristics were assessed in 1983, and child abuse was determined in 2000-2001 based on retrospective self-report. Results showed that PA and SA were associated with several factors indicative of social disadvantage in childhood. Multilevel regression analyses for years of education revealed a significant estimate for severe PA based on the unadjusted model (-0.60 years, 95% CI = [-0.45, -0.76]); estimates for non-severe PA (0.05 years, CI = [-0.15, 0.26]) and SA (-0.25 years, CI = [-0.09, -0.42]) were not significant. In the adjusted full model, the only association to reach significance was between severe PA and reduced years of education (-0.31 years, CI = [-0.18, -0.44]). Multilevel regression analyses for failure to graduate from high school showed significant unadjusted estimates for severe PA (OR = 1.77, 95% CI = [1.21, 2.58]) and non-severe PA (OR = 1.61, CI = [1.01, 2.57]); SA was not associated with this outcome (OR = 1.40, CI = [0.94, 2.07]). In the adjusted full models, there were no significant associations between child abuse variables and failure to graduate. The magnitude of effect of PA on both outcomes was reduced largely by child individual characteristics. These findings generally support earlier research, indicating the adverse effects of child maltreatment on educational attainment. Of particular note, severe PA was associated with reduced years of education after accounting for a comprehensive set of potential confounding variables and child characteristics. © The Author(s) 2014.

A New Method for Partial Correction of Residual Confounding in Time-Series and Other Observational Studies.

PubMed

Flanders, W Dana; Strickland, Matthew J; Klein, Mitchel

2017-05-15

Methods exist to detect residual confounding in epidemiologic studies. One requires a negative control exposure with 2 key properties: 1) conditional independence of the negative control and the outcome (given modeled variables) absent confounding and other model misspecification, and 2) associations of the negative control with uncontrolled confounders and the outcome. We present a new method to partially correct for residual confounding: When confounding is present and our assumptions hold, we argue that estimators from models that include a negative control exposure with these 2 properties tend to be less biased than those from models without it. Using regression theory, we provide theoretical arguments that support our claims. In simulations, we empirically evaluated the approach using a time-series study of ozone effects on asthma emergency department visits. In simulations, effect estimators from models that included the negative control exposure (ozone concentrations 1 day after the emergency department visit) had slightly or modestly less residual confounding than those from models without it. Theory and simulations show that including the negative control can reduce residual confounding, if our assumptions hold. Our method differs from available methods because it uses a regression approach involving an exposure-based indicator rather than a negative control outcome to partially correct for confounding. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association of Combined Patterns of Tobacco and Cannabis Use in Adolescence With Psychotic Experiences

PubMed Central

Gage, Suzanne H.; Heron, Jon; Hickman, Matthew; Lewis, Glyn; Munafò, Marcus R.; Zammit, Stanley

2018-01-01

Importance There is concern about potentially causal effects of tobacco use on psychosis, but epidemiological studies have been less robust in attempts to minimize effects of confounding than studies of cannabis use have been. Objectives To examine the association of patterns of cigarette and cannabis use with preceding and subsequent psychotic experiences, and to compare effects of confounding across these patterns. Design, Setting, and Participants This cohort study used data from the Avon Longitudinal Study of Parents and Children, which initially consisted of 14 062 children. Data were collected periodically from September 6, 1990, with collection ongoing, and analyzed from August 8, 2016, through June 14, 2017. Cigarette and cannabis use data were summarized using longitudinal latent class analysis to identify longitudinal classes of substance use. Associations between classes and psychotic experiences at age 18 years were assessed. Exposures Depending on the analysis model, exposures were longitudinal classes of substance use or psychotic experiences at age 12 years. Main Outcomes and Measures Logistic regression was used to examine the associations between substance use longitudinal classes and subsequent onset of psychotic experiences. Results Longitudinal classes were derived using 5300 participants (56.1% female) who had at least 3 measures of cigarette and cannabis use from ages 14 to 19 years. Prior to adjusting for a range of potential confounders, there was strong evdience that early-onset cigarette-only use (4.3%), early-onset cannabis use (3.2%), and late-onset cannabis use (11.9%) (but not later-onset cigarette-only use [14.8%]) latent classes were associated with increased psychotic experiences compared with nonusers (65.9%) (omnibus P < .001). After adjusting for confounders, the association for early-onset cigarette-only use attenuated substantially (unadjusted odds ratio [OR], 3.03; 95% CI, 1.13-8.14; adjusted OR, 1.78; 95% CI, 0.54-5.88), whereas those for early-onset cannabis use (adjusted OR, 3.70; 95% CI, 1.66-8.25) and late-onset cannabis use (adjusted OR, 2.97; 95% CI, 1.63-5.40) remained consistent. Conclusions and Relevance In this study, our findings indicate that while individuals who use cannabis or cigarettes during adolescence have an increased risk of subsequent psychotic experiences, epidemiological evidence is substantively more robust for cannabis use than it is for tobacco use. PMID:29344610

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology.

PubMed

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant ( p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation.

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

PubMed Central

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant (p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation. PMID:28824498

The effects of housework on the health of retired older adults: a preliminary investigation from the Tongji-Dongfeng cohort study, China.

PubMed

Wen, Xiaopiao; Liang, Yuan; Zhu, Jiang; Wu, Tangchun

2013-01-01

The aim of the current study was to explore the relationship between housework and health of retired older adults, and to provide new evidences and clues for the effects of housework on health. The data came from the baseline survey of the Tongji-Dongfeng Cohort Study with 25,501 participants. The independent variable was housework including child care, elder care, grocery shopping & cooking, and washing clothes & cleaning house. The dependent variable was self-reported two-week illness. Age, education, marital status, smoking and drinking were used as potential confounding variables. There are gender differences in the four types of housework, with higher prevalence among women than among men. The prevalence of two-week illness in women was higher than that in men. After adjusting for potential confounding variables, the four types of housework had almost no significant effects on two-week illness, except for washing clothes & cleaning house with a negative effect for women (OR = 1.17, 95% CI 1.06-1.29). The association of housework with health, especially of child care, elder care, and grocery shopping & cooking without significance and of washing clothes & cleaning house with significance for women, would provide a valuable clue for in-depth study of housework, namely the effects of housework on health would be subdivided into the dimensions of psychological and social activity besides physical activity, and it may not be suitable to simply classify housework as a kind of exercise.

Selection and Socialization Effects in Early Adolescent Alcohol Use: A Propensity Score Analysis

PubMed Central

Scalco, Matthew D.; Trucco, Elisa M.; Coffman, Donna L.; Colder, Craig R.

2015-01-01

The robust correlation between peer and adolescent alcohol use (AU) has been taken as evidence for both socialization and selection processes in the etiology of adolescent AU. Accumulating evidence from studies using a diverse range of methodological and statistical approaches suggests that both processes are involved. A major challenge in testing whether peer AU predicts an adolescent's drinking (socialization) or whether an adolescent's drinking predicts peer AU (selection) is the myriad of potentially confounding factors that might lead to an overestimation of socialization and selection effects. After creating AU transition groups based on peer and adolescent AU across two waves (N = 765; age = 10-15; 53% female), we test whether transitions into AU by adolescents and peers predict later peer and adolescent AU respectively, using (1) propensity score analysis to balance transition groups on 26 potential confounds, (2) a longitudinal design with three waves to establish temporal precedence, and (3) both adolescent (target) and peer self-report of peer AU to disentangle effects attributable to shared reporter bias. Both selection and socialization were supported using both peer self-report of AU and adolescent-report of peer AU. Although cross-sectional analyses suggested peer self-reported models were associated with smaller effects than perceived peer AU, longitudinal analyses suggest a similar sized effect across reporter of peer AU for both selection and socialization. The implications of these findings for the etiology and treatment of adolescent AU are discussed. PMID:25601099

Gardening and age-related weight gain: Results from a cross-sectional survey of Denver residents.

PubMed

Litt, Jill S; Lambert, Jeffrey Richard; Glueck, Deborah H

2017-12-01

This study examined whether gardening modifies the association between age and body mass index (BMI). We used data from the Neighborhood Environments and Health Survey, which was conducted in Denver (N = 469) between 2006 and 2007. We fit two general linear mixed models. The base model had BMI in kg/m 2 as the outcome, and age, an indicator variable for non-gardening status and the age-by-non-gardening status interaction as predictors. The adjusted model included as covariates the potential confounders of education, ethnicity and self-reported health. We assessed self-selection bias and confounding. BMI was 27.18 kg/m 2 for non-gardeners, 25.62 kg/m 2 for home gardeners, and 24.17 kg/m 2 for community gardeners. In the base model, a statistically significant association was observed between age and BMI for non-gardeners but not for the combined community and home gardening group (F = 9.27, ndf = 1, ddf = 441, p = 0.0025). In the adjusted model, the association between age and BMI in non-gardeners was not statistically significant (F = 1.72, ndf = 1, ddf = 431, p = 0.1908). Gardeners differed on social and demographic factors when compared to non-gardeners. The results from the base model are consistent with the hypothesis that gardening might offset age-related weight gain. However, the cross-sectional design does not permit differentiation of true causal effects from the possible effects of bias and confounding. As a follow-up study, to remove bias and confounding, we are conducting a randomized clinical trial of community gardening in Denver.

Normality of upper and lower peripheral pulse transit time of normotensive and hypertensive children.

PubMed

Foo, Jong Yong Abdiel

2007-08-01

The ankle-brachial index (ABI) is known to be indicative of sub-clinical peripheral arterial diseases that are correlated with cardiovascular disease risk factors like atherosclerosis or ischemic extremity. Due to its occluding measurement nature, this may not be appealing to less cooperative patients when multiple prolonged screening is required. A simple and non-intrusive approach termed pulse transit time ratio (PTTR) has recently shown to be potential surrogate marker for the prolonged ABI measurement. Other studies have also suggested that subjects with hypertension have stiffer arterial wall and thereby can confound transit time related parameters. Thus, it becomes important to understand the PTTR normality and difference of hypertensive children when compared to those measured from normotensive children. About 55 normotensive (39 male; aged 8.4 +/- 2.3 yr) and 4 hypertensive (4 male; aged 5-10 yr) Caucasian children were recruited from the same geographical location. A customized device was used to compute pulse transit time related measurements. Since the PTTR approach produced a delta value that was similar to that of ABI, possible inter-subject physiologic differences had limited confounding effects on the derived PTTR parameter. The obtained transit time measurements from the hypertensive children had lower pulse transit time value when compared to their normotensive counterparts. However, the statistical analysis indicated that they had insignificant PTTR difference (p > 0.01) from those seen in the normotensive children. The findings herein suggest that stiffer arterial wall may have confounding effects on the derived transit time related measurements but it is limited on the PTTR parameter. Similar to the ABI approach, PTTR may be only confounded by abnormal local changes in either of the measured peripheral arterial wall. Hence, the PTTR technique shows promise to be an ABI marker from this perspective.

A Framework for Estimating Causal Effects in Latent Class Analysis: Is There a Causal Link Between Early Sex and Subsequent Profiles of Delinquency?

PubMed Central

Lanza, Stephanie T.; Coffman, Donna L.

2013-01-01

Prevention scientists use latent class analysis (LCA) with increasing frequency to characterize complex behavior patterns and profiles of risk. Often, the most important research questions in these studies involve establishing characteristics that predict membership in the latent classes, thus describing the composition of the subgroups and suggesting possible points of intervention. More recently, prevention scientists have begun to adopt modern methods for drawing causal inference from observational data because of the bias that can be introduced by confounders. This same issue of confounding exists in any analysis of observational data, including prediction of latent class membership. This study demonstrates a straightforward approach to causal inference in LCA that builds on propensity score methods. We demonstrate this approach by examining the causal effect of early sex on subsequent delinquency latent classes using data from 1,890 adolescents in 11th and 12th grade from wave I of the National Longitudinal Study of Adolescent Health. Prior to the statistical adjustment for potential confounders, early sex was significantly associated with delinquency latent class membership for both genders (p=0.02). However, the propensity score adjusted analysis indicated no evidence for a causal effect of early sex on delinquency class membership (p=0.76) for either gender. Sample R and SAS code is included in an Appendix in the ESM so that prevention scientists may adopt this approach to causal inference in LCA in their own work. PMID:23839479

A framework for estimating causal effects in latent class analysis: is there a causal link between early sex and subsequent profiles of delinquency?

PubMed

Butera, Nicole M; Lanza, Stephanie T; Coffman, Donna L

2014-06-01

Prevention scientists use latent class analysis (LCA) with increasing frequency to characterize complex behavior patterns and profiles of risk. Often, the most important research questions in these studies involve establishing characteristics that predict membership in the latent classes, thus describing the composition of the subgroups and suggesting possible points of intervention. More recently, prevention scientists have begun to adopt modern methods for drawing causal inference from observational data because of the bias that can be introduced by confounders. This same issue of confounding exists in any analysis of observational data, including prediction of latent class membership. This study demonstrates a straightforward approach to causal inference in LCA that builds on propensity score methods. We demonstrate this approach by examining the causal effect of early sex on subsequent delinquency latent classes using data from 1,890 adolescents in 11th and 12th grade from wave I of the National Longitudinal Study of Adolescent Health. Prior to the statistical adjustment for potential confounders, early sex was significantly associated with delinquency latent class membership for both genders (p = 0.02). However, the propensity score adjusted analysis indicated no evidence for a causal effect of early sex on delinquency class membership (p = 0.76) for either gender. Sample R and SAS code is included in an Appendix in the ESM so that prevention scientists may adopt this approach to causal inference in LCA in their own work.

Spatial variation in mortality risk for haematological malignancies near a petrochemical refinery: a population-based case-control study

PubMed Central

Di Salvo, Francesca; Meneghini, Elisabetta; Vieira, Veronica; Baili, Paolo; Mariottini, Mauro; Baldini, Marco; Micheli, Andrea; Sant, Milena

2015-01-01

Introduction The study investigated the geographic variation of mortality risk for hematological malignancies (HMs) in order to identify potential high-risk areas near an Italian petrochemical refinery. Material and methods A population-based case-control study was conducted and residential histories for 171 cases and 338 sex- and age-matched controls were collected. Confounding factors were obtained from interviews with consenting relatives for 109 HM deaths and 267 controls. To produce risk mortality maps, two different approaches were applied. We mapped (1) adptive kernel density relative risk estimation (KDE) for case-control studies which estimates a spatial relative risk function using the ratio between cases and controls’ densities, and (2) estimated odds ratios for case-control study data using generalized additive models (GAMs) to smooth the effect of location, a proxy for exposure, while adjusting for confounding variables. Results No high-risk areas for HM mortality were identified among all subjects (men and women combined), by applying both approaches. Using the adaptive KDE approach, we found a significant increase in death risk only among women in a large area 2–6 km southeast of the refinery and the application of GAMs also identified a similarly-located significant high-risk area among women only (global p-value<0.025). Potential confounding risk factors we considered in the GAM did not alter the results. Conclusion Both approaches identified a high-risk area close to the refinery among women only. Those spatial methods are useful tools for public policy management to determine priority areas for intervention. Our findings suggest several directions for further research in order to identify other potential environmental exposures that may be assessed in forthcoming studies based on detailed exposure modeling. PMID:26073202

Evaluation of Non-Lethal Effects of N2 Bubbles on Marine Mammal Health and the Potential Role of Immune Activity in Facilitating the Development of Dive Related Injury

DTIC Science & Technology

2015-09-30

control for confounding effects of changing physiological status. Cortisol will be measured using a commercial enzyme immunoassay ( EIA ) and plasma...complement activity in plasma and serum has been tested using zymosan (Sigma Aldrich) which is a known activator of complement. Validation of the EIA ...expected to be underway by November 2015. Data collection for objective 3 will occur during project year 2. RESULTS EIA kits for seal

Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

PubMed Central

Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

2015-01-01

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered. PMID:26759790

Mothers' spanking of 3-year-old children and subsequent risk of children's aggressive behavior.

PubMed

Taylor, Catherine A; Manganello, Jennifer A; Lee, Shawna J; Rice, Janet C

2010-05-01

The goal was to examine the association between the use of corporal punishment (CP) against 3-year-old children and subsequent aggressive behavior among those children. Respondents (N = 2461) participated in the Fragile Families and Child Well-being Study (1998-2005), a population-based, birth cohort study of children born in 20 large US cities. Maternal reports of CP, children's aggressive behaviors at 3 and 5 years of age, and a host of key demographic features and potential confounding factors, including maternal child physical maltreatment, psychological maltreatment, and neglect, intimate partner aggression victimization, stress, depression, substance use, and consideration of abortion, were assessed. Frequent use of CP (ie, mother's use of spanking more than twice in the previous month) when the child was 3 years of age was associated with increased risk for higher levels of child aggression when the child was 5 years of age (adjusted odds ratio: 1.49 [95% confidence interval: 1.2-1.8]; P < .0001), even with controlling for the child's level of aggression at age 3 and the aforementioned potential confounding factors and key demographic features. Despite American Academy of Pediatrics recommendations to the contrary, most parents in the United States approve of and have used CP as a form of child discipline. The current findings suggest that even minor forms of CP, such as spanking, increase risk for increased child aggressive behavior. Importantly, these findings cannot be attributed to possible confounding effects of a host of other maternal parenting risk factors.

Association between Exposure to Electromagnetic Fields from High Voltage Transmission Lines and Neurobehavioral Function in Children

PubMed Central

Huang, Jiongli; Tang, Tiantong; Hu, Guocheng; Zheng, Jing; Wang, Yuyu; Wang, Qiang; Su, Jing; Zou, Yunfeng; Peng, Xiaowu

2013-01-01

Background Evidence for a possible causal relationship between exposure to electromagnetic fields (EMF) emitted by high voltage transmission (HVT) lines and neurobehavioral dysfunction in children is insufficient. The present study aims to investigate the association between EMF exposure from HVT lines and neurobehavioral function in children. Methods Two primary schools were chosen based on monitoring data of ambient electromagnetic radiation. A cross-sectional study with 437 children (9 to 13 years old) was conducted. Exposure to EMF from HVT lines was monitored at each school. Information was collected on possible confounders and relevant exposure predictors using standardized questionnaires. Neurobehavioral function in children was evaluated using established computerized neurobehavioral tests. Data was analyzed using multivariable regression models adjusted for relevant confounders. Results After controlling for potential confounding factors, multivariable regression revealed that children attending a school near 500 kV HVT lines had poorer performance on the computerized neurobehavioral tests for Visual Retention and Pursuit Aiming compared to children attending a school that was not in close proximity to HVT lines. Conclusions The results suggest long-term low-level exposure to EMF from HVT lines might have a negative impact on neurobehavioral function in children. However, because of differences in results only for two of four tests achieved statistical significance and potential limitations, more studies are needed to explore the effects of exposure to extremely low frequency EMF on neurobehavioral function and development in children. PMID:23843999

Youth unemployment and functional somatic symptoms in adulthood: results from the Northern Swedish cohort.

PubMed

Brydsten, Anna; Hammarström, Anne; Strandh, Mattias; Johansson, Klara

2015-10-01

Little is known about the possible long-term health consequences of youth unemployment. Research indicates that unemployment may lead to socioeconomic downward mobility and mental health problems, but we still lack knowledge of the long-term health consequences of youth unemployment. This article examines the potential long-term association between youth unemployment and functional somatic symptoms in adulthood. The 'Northern Swedish cohort' was used with data from five data collections, from 1981 (age 16) until 2007 (age 42). Youth unemployment was measured as months in unemployment between age 16 and 21, and health outcome as functional somatic symptoms (an index of 10 items of self-reported symptoms). Linear regression was used to analyse the relationship between months in youth unemployment and functional somatic symptoms at age 21 and age 42, stratified for women and men and adjusted for potential confounders, such as time spent in education at age 21 and later unemployment between age 21 and 42. Youth unemployment was significantly related to functional somatic symptoms at age 21 for men after controlling for confounders, but not for women. Among men, the association remained for functional somatic symptoms at age 42, after controlling for confounders. Adolescence seems to be a sensitive period during which unemployment could have remaining health effects in adulthood, at least for men, though assumptions of causality are tentative and more research is needed. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification

PubMed Central

Dunne, Philip D.; Alderdice, Matthew; O'Reilly, Paul G.; Roddy, Aideen C.; McCorry, Amy M. B.; Richman, Susan; Maughan, Tim; McDade, Simon S.; Johnston, Patrick G.; Longley, Daniel B.; Kay, Elaine; McArt, Darragh G.; Lawler, Mark

2017-01-01

Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility of these signatures to the confounding effects of ITH using gene expression microarray data obtained from multiple tumour regions of a cohort of 24 patients, including central tumour, the tumour invasive front and lymph node metastasis. Sample clustering alongside correlative assessment revealed variation in the ability of each signature to cluster samples according to patient-of-origin rather than region-of-origin within the multi-region dataset. Signatures focused on cancer-cell intrinsic gene expression were found to produce more clinically useful, patient-centred classifiers, as exemplified by the CRC intrinsic signature (CRIS), which robustly clustered samples by patient-of-origin rather than region-of-origin. These findings highlight the potential of cancer-cell intrinsic signatures to reliably stratify CRC patients by minimising the confounding effects of stromal-derived ITH. PMID:28561046

phMRI: methodological considerations for mitigating potential confounding factors

PubMed Central

Bourke, Julius H.; Wall, Matthew B.

2015-01-01

Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome. PMID:25999812

Multivariate Analysis To Quantify Species in the Presence of Direct Interferents: Micro-Raman Analysis of HNO 3 in Microfluidic Devices

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

Lines, Amanda M.; Nelson, Gilbert L.; Casella, Amanda J.

Microfluidic devices are a growing field with significant potential for application to small scale processing of solutions. Much like large scale processing, fast, reliable, and cost effective means of monitoring the streams during processing are needed. Here we apply a novel Micro-Raman probe to the on-line monitoring of streams within a microfluidic device. For either macro or micro scale process monitoring via spectroscopic response, there is the danger of interfering or confounded bands obfuscating results. By utilizing chemometric analysis, a form of multivariate analysis, species can be accurately quantified in solution despite the presence of overlapping or confounded spectroscopic bands.more » This is demonstrated on solutions of HNO 3 and NaNO 3 within micro-flow and microfluidic devices.« less

Assessing mediation using marginal structural models in the presence of confounding and moderation

PubMed Central

Coffman, Donna L.; Zhong, Wei

2012-01-01

This paper presents marginal structural models (MSMs) with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of non-randomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PMID:22905648

Assessing mediation using marginal structural models in the presence of confounding and moderation.

PubMed

Coffman, Donna L; Zhong, Wei

2012-12-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of nonrandomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PsycINFO Database Record (c) 2013 APA, all rights reserved.

THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2014-01-01

Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

Cesarean section without medical indication and risk of childhood asthma, and attenuation by breastfeeding.

PubMed

Chu, Shuyuan; Chen, Qian; Chen, Yan; Bao, Yixiao; Wu, Min; Zhang, Jun

2017-01-01

Previous studies suggest that caesarean section (CS) may increase the risk of asthma in children, but none of them could preclude potential confounding effects of underlying medical indications for CS. We aim to assess the association between CS itself (without medical indications) and risk of childhood asthma. We conducted a hospital-based case-control study on childhood asthma with 573 cases and 812 controls in Shanghai. Unconditional logistic regression models in SAS were employed to control for potential confounders. Our study found that CS without medical indication was significantly associated with elevated asthma risk (adjusted OR = 1.58 [95% CI 1.17-2.13]). However, this risk was attenuated in children fed by exclusive breastfeeding in the first six months after birth (adjusted OR = 1.39 [95% CI 0.92-2.10]). In contrast, the risk was more prominent in children with non-exclusive breastfeeding or bottle feeding (adjusted OR = 1.91 [95% CI 1.22-2.99]). CS without medical indication was associated with an increased risk of childhood asthma. Exclusive breastfeeding in infancy may attenuate this risk.

Disconcordance in Statistical Models of Bisphenol A and Chronic Disease Outcomes in NHANES 2003-08

PubMed Central

Casey, Martin F.; Neidell, Matthew

2013-01-01

Background Bisphenol A (BPA), a high production chemical commonly found in plastics, has drawn great attention from researchers due to the substance’s potential toxicity. Using data from three National Health and Nutrition Examination Survey (NHANES) cycles, we explored the consistency and robustness of BPA’s reported effects on coronary heart disease and diabetes. Methods And Findings We report the use of three different statistical models in the analysis of BPA: (1) logistic regression, (2) log-linear regression, and (3) dose-response logistic regression. In each variation, confounders were added in six blocks to account for demographics, urinary creatinine, source of BPA exposure, healthy behaviours, and phthalate exposure. Results were sensitive to the variations in functional form of our statistical models, but no single model yielded consistent results across NHANES cycles. Reported ORs were also found to be sensitive to inclusion/exclusion criteria. Further, observed effects, which were most pronounced in NHANES 2003-04, could not be explained away by confounding. Conclusions Limitations in the NHANES data and a poor understanding of the mode of action of BPA have made it difficult to develop informative statistical models. Given the sensitivity of effect estimates to functional form, researchers should report results using multiple specifications with different assumptions about BPA measurement, thus allowing for the identification of potential discrepancies in the data. PMID:24223205

Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa)

PubMed Central

Zuccolo, Luisa; DeRoo, Lisa A.; Wills, Andrew K.; Davey Smith, George; Suren, Pål; Roth, Christine; Stoltenberg, Camilla; Magnus, Per

2016-01-01

Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999–2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy. PMID:28008975

Developmental Effects of Incentives on Response Inhibition

PubMed Central

Geier, Charles F.; Luna, Beatriz

2012-01-01

Inhibitory control and incentive processes underlie decision-making, yet few studies have explicitly examined their interaction across development. Here, the effects of potential rewards and losses on inhibitory control in sixty-four adolescents (13-17-year-olds) and forty-two young adults (18-29-year-olds) were examined using an incentivized antisaccade task. Notably, measures were implemented to minimize age-related differences in reward valuation and potentially confounding motivation effects. Incentives affected antisaccade metrics differently across the age groups. Younger adolescents generated more errors than adults on reward trials, but all groups performed well on loss trials. Adolescent saccade latencies also differed from adults across the range of reward trials. Overall, results suggest persistent immaturities in the integration of reward and inhibitory control processes across adolescence. PMID:22540668

Early Childhood Lead Exposure and Academic Achievement: Evidence From Detroit Public Schools, 2008–2010

PubMed Central

Baker, Harolyn W.; Tufts, Margaret; Raymond, Randall E.; Salihu, Hamisu; Elliott, Michael R.

2013-01-01

Objectives. We assessed the long-term effect of early childhood lead exposure on academic achievement in mathematics, science, and reading among elementary and junior high school children. Methods. We linked early childhood blood lead testing surveillance data from the Detroit Department of Health and Wellness Promotion to educational testing data from the Detroit, Michigan, public schools. We used the linked data to investigate the effect of early childhood lead exposure on academic achievement among school-aged children, both marginally and adjusted for grade level, gender, race, language, maternal education, and socioeconomic status. Results. High blood lead levels before age 6 years were strongly associated with poor academic achievement in grades 3, 5, and 8. The odds of scoring less than proficient for those whose blood lead levels were greater than 10 micrograms per deciliter were more than twice the odds for those whose blood lead levels were less than 1 micrograms per deciliter after adjustment for potential confounders. Conclusions. Early childhood lead exposure was negatively associated with academic achievement in elementary and junior high school, after adjusting for key potential confounders. The control of lead poisoning should focus on primary prevention of lead exposure in children and development of special education programs for students with lead poisoning. PMID:23327265

Effect decomposition in the presence of an exposure-induced mediator-outcome confounder

PubMed Central

VanderWeele, Tyler J.; Vansteelandt, Stijn; Robins, James M.

2014-01-01

Methods from causal mediation analysis have generalized the traditional approach to direct and indirect effects in the epidemiologic and social science literature by allowing for interaction and non-linearities. However, the methods from the causal inference literature have themselves been subject to a major limitation in that the so-called natural direct and indirect effects that are employed are not identified from data whenever there is a variable that is affected by the exposure, which also confounds the relationship between the mediator and the outcome. In this paper we describe three alternative approaches to effect decomposition that give quantities that can be interpreted as direct and indirect effects, and that can be identified from data even in the presence of an exposure-induced mediator-outcome confounder. We describe a simple weighting-based estimation method for each of these three approaches, illustrated with data from perinatal epidemiology. The methods described here can shed insight into pathways and questions of mediation even when an exposure-induced mediator-outcome confounder is present. PMID:24487213

Oxidative stress in drug-naïve first episode patients with schizophrenia and major depression: effects of disease acuity and potential confounders.

PubMed

Jordan, Wolfgang; Dobrowolny, Henrik; Bahn, Sabine; Bernstein, Hans-Gert; Brigadski, Tanja; Frodl, Thomas; Isermann, Berend; Lessmann, Volkmar; Pilz, Jürgen; Rodenbeck, Andrea; Schiltz, Kolja; Schwedhelm, Edzard; Tumani, Hayrettin; Wiltfang, Jens; Guest, Paul C; Steiner, Johann

2018-03-01

Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43). Possible confounding factors were considered, and patients were followed-up after 6 weeks of treatment. No differences were observed regarding 8-OH-2-dG, MDA and GST. At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. However, 8-iso-PGF2α was associated with smoking, endocrine stress axis activation, C-reactive protein levels and low plasma concentrations of brain-derived neurotrophic factor. This study suggests a role of lipid peroxidation particularly in drug-naïve acutely ill schizophrenia patients and highlights the importance of taking into account other confounding factors in biomarker studies.

Comparison between treatment effects in a randomised controlled trial and an observational study using propensity scores in primary care.

PubMed

Stuart, Beth L; Grebel, Louise En; Butler, Christopher C; Hood, Kerenza; Verheij, Theo J M; Little, Paul

2017-09-01

Although randomised controlled trials (RCTs) are considered 'gold standard' evidence, they are not always feasible or appropriate, and may represent a select population. Observational studies provide a useful alternative to enhance applicability, but results can be biased due to confounding. To explore the utility of propensity scores for causal inference in an observational study. Comparison of the effect of amoxicillin on key outcomes in an international RCT and observational study of lower respiratory tract infections. Propensity scores were calculated and applied as probability weights in the analyses. The adjusted results were compared with the effects reported in the RCT. Groups were well balanced in the RCT but significantly imbalanced in the observational study, with evidence of confounding by indication: patients receiving antibiotics tended to be older and more unwell at baseline consultation. In the trial duration of symptoms (hazard ratio 1.06, 95% CI = 0.96 to 1.18) and symptom severity (-0.07, 95% CI = -0.15 to 0.007) did not differ between groups. Weighting by propensity score in the observational study resulted in very similar estimates of effect: duration of symptoms (hazard ratio 1.06, 95% CI = 0.80 to 1.40) and difference for symptom severity (-0.07, 95% CI = -0.34 to 0.20). The observational study, after conditioning on propensity score, echoed the trial results. Provided that detailed information is available on potential sources of confounding, effects of interventions can probably be assessed reasonably well in observational datasets, allowing them to be more directly compared with the results of RCTs. © British Journal of General Practice 2017.

Treatment effect heterogeneity for univariate subgroups in clinical trials: Shrinkage, standardization, or else

PubMed Central

Varadhan, Ravi; Wang, Sue-Jane

2016-01-01

Treatment effect heterogeneity is a well-recognized phenomenon in randomized controlled clinical trials. In this paper, we discuss subgroup analyses with prespecified subgroups of clinical or biological importance. We explore various alternatives to the naive (the traditional univariate) subgroup analyses to address the issues of multiplicity and confounding. Specifically, we consider a model-based Bayesian shrinkage (Bayes-DS) and a nonparametric, empirical Bayes shrinkage approach (Emp-Bayes) to temper the optimism of traditional univariate subgroup analyses; a standardization approach (standardization) that accounts for correlation between baseline covariates; and a model-based maximum likelihood estimation (MLE) approach. The Bayes-DS and Emp-Bayes methods model the variation in subgroup-specific treatment effect rather than testing the null hypothesis of no difference between subgroups. The standardization approach addresses the issue of confounding in subgroup analyses. The MLE approach is considered only for comparison in simulation studies as the “truth” since the data were generated from the same model. Using the characteristics of a hypothetical large outcome trial, we perform simulation studies and articulate the utilities and potential limitations of these estimators. Simulation results indicate that Bayes-DS and Emp-Bayes can protect against optimism present in the naïve approach. Due to its simplicity, the naïve approach should be the reference for reporting univariate subgroup-specific treatment effect estimates from exploratory subgroup analyses. Standardization, although it tends to have a larger variance, is suggested when it is important to address the confounding of univariate subgroup effects due to correlation between baseline covariates. The Bayes-DS approach is available as an R package (DSBayes). PMID:26485117

Social desirability bias in self-reported dietary, physical activity and weight concerns measures in 8- to 10-year-old African-American girls: results from the Girls Health Enrichment Multisite Studies (GEMS).

PubMed

Klesges, Lisa M; Baranowski, Tom; Beech, Bettina; Cullen, Karen; Murray, David M; Rochon, Jim; Pratt, Charlotte

2004-05-01

Social desirability (SocD) may bias children's self-reported health behaviors and attitudes and confound relationships with health outcome measures. Ninety-five, 8- to 10-year-old African-American girls completed dietary recalls, a physical activity checklist, psychosocial questionnaires related to diet, and physical activity; and 3 days of physical activity monitoring. Potential SocD construct bias was investigated by comparing designated criterion measures of physical activity, beverage intake, and body mass index (BMI) with respective self-reported measures related to activity, beverage preferences, and body image and weight concerns in cross-sectional regression models. Potential confounding by SocD of associations between self-reported behaviors with BMI was assessed using change-in-coefficient regression analyses. Controlling for age and BMI, overestimates of self-reported activity (P = 0.02), underestimates of sweetened beverage preferences (P = 0.02), and lower ratings of weight concerns and dieting behaviors (P's < 0.05) were related to SocD. Confounding by SocD of associations between self-reported physical activity and energy intake with BMI was found. In 8- to 10-year-old African-American girls, SocD was found to bias self-reports of diet and physical activity and confound associations between BMI and self-reported physical activity and energy intake. Methods to measure and control SocD bias are needed to reduce potential distortion of relationships between diet and physical activity and health outcomes.

Causal Methods for Observational Research: A Primer.

PubMed

Almasi-Hashiani, Amir; Nedjat, Saharnaz; Mansournia, Mohammad Ali

2018-04-01

The goal of many observational studies is to estimate the causal effect of an exposure on an outcome after adjustment for confounders, but there are still some serious errors in adjusting confounders in clinical journals. Standard regression modeling (e.g., ordinary logistic regression) fails to estimate the average effect of exposure in total population in the presence of interaction between exposure and covariates, and also cannot adjust for time-varying confounding appropriately. Moreover, stepwise algorithms of the selection of confounders based on P values may miss important confounders and lead to bias in effect estimates. Causal methods overcome these limitations. We illustrate three causal methods including inverse-probability-of-treatment-weighting (IPTW) and parametric g-formula, with an emphasis on a clever combination of these 2 methods: targeted maximum likelihood estimation (TMLE) which enjoys a double-robust property against bias. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice.

PubMed

Ingvorsen, C; Karp, N A; Lelliott, C J

2017-04-10

Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes.

Population-based evaluation of the effectiveness of two regimens for emergency contraception.

PubMed

Leung, Vivian W Y; Soon, Judith A; Lynd, Larry D; Marra, Carlo A; Levine, Marc

2016-06-01

To estimate and compare the effectiveness of the levonorgestrel and Yuzpe regimens for hormonal emergency contraception in routine clinical practice. A retrospective population-based study included women who accessed emergency contraceptives for immediate use prescribed by community pharmacists in British Columbia, Canada, between December 2000 and December 2002. Linked administrative healthcare data were used to discern the timings of menses, unprotected intercourse, and any pregnancy-related health services. A panel of experts evaluated the compatibility of observed pregnancies with the timing of events. The two regimens were compared with statistical adjustments for potential confounding. Among 7493 women in the cohort, 4470 (59.7%) received levonorgestrel and 3023 (40.3%) the Yuzpe regimen. There were 99 (2.2%) compatible pregnancies in the levonorgestrel group and 94 (3.1%) in the Yuzpe group (P=0.017). The estimated odds ratio for levonorgestrel compared with the Yuzpe regimen after adjusting for potential confounders was 0.64 (95% confidence interval 0.47-0.87). Against an expected pregnancy rate of approximately 5%, the relative and absolute risk reductions were 56.0% and 2.8%, respectively, for levonorgestrel and 36.7% and 1.8% for the Yuzpe regimen. The levonorgestrel regimen is more effective than the Yuzpe regimen in routine use. The data suggest that both regimens are less effective than has been observed in randomized trials. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

More Precise Estimation of Lower-Level Interaction Effects in Multilevel Models.

PubMed

Loeys, Tom; Josephy, Haeike; Dewitte, Marieke

2018-01-01

In hierarchical data, the effect of a lower-level predictor on a lower-level outcome may often be confounded by an (un)measured upper-level factor. When such confounding is left unaddressed, the effect of the lower-level predictor is estimated with bias. Separating this effect into a within- and between-component removes such bias in a linear random intercept model under a specific set of assumptions for the confounder. When the effect of the lower-level predictor is additionally moderated by another lower-level predictor, an interaction between both lower-level predictors is included into the model. To address unmeasured upper-level confounding, this interaction term ought to be decomposed into a within- and between-component as well. This can be achieved by first multiplying both predictors and centering that product term next, or vice versa. We show that while both approaches, on average, yield the same estimates of the interaction effect in linear models, the former decomposition is much more precise and robust against misspecification of the effects of cross-level and upper-level terms, compared to the latter.

The effect of ambient lighting on Laser Doppler Imaging of a standardized cutaneous injury model.

PubMed

Pham, Alan Chuong Q; Hei, Erik La; Harvey, John G; Holland, Andrew Ja

2017-01-01

The aim of this study was to investigate the potential confounding effects of four different types of ambient lighting on the results of Laser Doppler Imaging (LDI) of a standardized cutaneous injury model. After applying a mechanical stimulus to the anterior forearm of a healthy volunteer and inducing a wheal and arteriolar flare (the Triple response), we used a Laser Doppler Line Scanner (LDLS) to image the forearm under four different types of ambient lighting: light-emitting-diode (LED), compact fluorescent lighting (CFL), halogen, daylight, and darkness as a control. A spectrometer was used to measure the intensity of light energy at 785 nm, the wavelength used by the scanner for measurement under each type of ambient lighting. Neither the LED nor CFL bulbs emitted detectable light energy at a wavelength of 785 nm. The color-based representation of arbitrary perfusion unit (APU) values of the Triple response measured by the scanner was similar between darkness, LED, and CFL light. Daylight emitted 2 mW at 785 nm, with a slight variation tending more towards lower APU values compared to darkness. Halogen lighting emitted 6 mW of light energy at 785 nm rendering the color-based representation impossible to interpret. Halogen lighting and daylight have the potential to confound results of LDI of cutaneous injuries whereas LED and CFL lighting did not. Any potential sources of daylight should be reduced and halogen lighting completely covered or turned off prior to wound imaging.

The Combined Effects of Measurement Error and Omitting Confounders in the Single-Mediator Model

PubMed Central

Fritz, Matthew S.; Kenny, David A.; MacKinnon, David P.

2016-01-01

Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator to outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. In order to explore the combined effect of measurement error and omitted confounders in the same model, the impact of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect. PMID:27739903

When can the cause of a population decline be determined?

PubMed

Hefley, Trevor J; Hooten, Mevin B; Drake, John M; Russell, Robin E; Walsh, Daniel P

2016-11-01

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time. © 2016 John Wiley & Sons Ltd/CNRS.

When can the cause of a population decline be determined?

USGS Publications Warehouse

Hefley, Trevor J.; Hooten, Mevin B.; Drake, John M.; Russell, Robin E.; Walsh, Daniel P.

2016-01-01

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time.

Mitochondrial genetic haplogroups and incident obesity: a longitudinal cohort study.

PubMed

Veronese, Nicola; Stubbs, Brendon; Koyanagi, Ai; Vaona, Alberto; Demurtas, Jacopo; Schofield, Patricia; Thompson, Trevor; Maggi, Stefania

2018-04-01

A small number of case-control studies have suggested that mitochondrial haplogroups could be associated with obesity. We examined whether obesity risk was influenced by mitochondrial haplogroup in a large North American cohort across an 8-year period. We conducted a longitudinal cohort study including individuals from the Osteoarthritis Initiative. Mitochondrial haplogroups were determined by sequencing and PCR-RFLP techniques using this nomenclature: HV, JT, KU, IWX, and super HV/others. The strength of the association between mitochondrial haplogroups and incident obesity was quantified with hazard ratios (HRs), adjusted for potential confounders using a Cox's regression analysis. Overall, 2342 non-obese Caucasian participants (56.7% women) with a mean ± SD age of 62.0 ± 9.5 years at baseline were included. During a median follow-up of 8 years, 334 individuals ( = 14.3% of baseline population) became obese. After adjusting for nine potential confounders, the haplogroups IWX carried a significant 48% higher risk of obesity (HR = 1.48; 95% CI: 1.02-2.39) compared to the HV haplotype (the most frequent type). Only the presence of the IWX haplogroups appears to be linked to increased obesity risk, independent of potential baseline confounders. Future cohort studies are needed to confirm these findings and to determine potential underlying mechanisms.

Duration perception of emotional stimuli: Using evaluative conditioning to avoid sensory confounds.

PubMed

Kliegl, Katrin M; Watrin, Luc; Huckauf, Anke

2015-01-01

It has been found that emotional pictures are estimated to last longer than neutral ones. However, emotional and neutral stimuli often differ in their physical characteristics, too. Since this might also affect time perception, we present a method disentangling a possible confounding regarding the processing of physically different stimulus material. In the evaluative condition paradigm, participants, at first, learnt the association of neutral images with a certain Landolt ring and of emotional images with another Landolt ring with a different gap position. The conditioned Landolt rings were subsequently used in a temporal bisection task. In two experiments, the results revealed a temporal overestimation of Landolt rings conditioned with emotional pictures compared to neutral pictures showing that the temporal overestimation of emotional stimuli cannot be attributed to perceptual differences between neutral and emotional stimuli. The method provides the potential for investigating emotional effects on various perceptual processes.

Startle reduces recall of a recently learned internal model.

PubMed

Wright, Zachary; Patton, James L; Ravichandran, Venn

2011-01-01

Recent work has shown that preplanned motor programs are released early from subcortical areas by the using a startling acoustic stimulus (SAS). Our question is whether this response might also contain a recently learned internal model, which draws on experience to predict and compensate for expected perturbations in a feedforward manner. Studies of adaptation to robotic forces have shown some evidence of this, but were potentially confounded by cocontraction caused by startle. We performed a new adaptation experiment using a visually distorted field that could not be confounded by cocontraction. We found that in all subjects that exhibited startle, the startle stimulus (1) reduced performance of the recently learned task (2) reduced after-effect magnitudes. Because startle reduced but did not eliminate the recall of learned control, we suggest that multiple neural centers (cortical and subcortical) are involved in such learning and adaptation, which can impact training areas such as piloting, teleoperation, sports, and rehabilitation. © 2011 IEEE

Fetal programming of mental health by acetaminophen? Response to the SMFM statement: prenatal acetaminophen use and ADHD.

PubMed

Olsen, Jørn; Liew, Zeyan

2017-12-01

A number of studies indicate that acetaminophen taken during pregnancy may have a programming effect on the fetal brain development. The potential adverse consequences may only surface to clinical detection years later. Should we act on these findings now or do we wait for additional evidence? Areas covered: We argue for action inspired by these well analyzed studies that are based on five prospective cohorts data collected from different countries. Several analytical options have been employed especially to address confounding, and all analyses have consistently suggested that confounding alone is an unlikely explanation for this disturbing observation. Expert opinion: Acetaminophen is often used for minor symptom or discomfort where the treatment has no strong indication and carries little, if any risk for the pregnant women. The harm of doing nothing may well exceed the harm for taking precautionary actions considering the consequences at stake.

Male fertility: psychiatric considerations.

PubMed

Hall, Elise; Burt, Vivien K

2012-02-01

To examine: 1) current knowledge on normal biologic variation of seminal parameters; 2) how stress and psychological factors affect sperm quality in fertile and infertile males; and 3) how mental illness and psychopharmacologic agents can affect male fertility. English-language Medline, Embase, and Psycinfo were searched for relevant publications (from 1970 to January 2011) for systematic review. None. None. None. Possible effects of stress, mood, and psychotropic medications on male factor fertility. Male-factor infertility is influenced by myriad factors (obesity, tobacco, etc.). Stress alone may reduce testosterone levels and spermatogenesis. Infertility assessment and treatment can lead to distress and negatively affect sperm samples. Available research has failed to control for potentially confounding variables. Although some trends have been identified, larger-scale studies that adequately control all confounding variables are needed before conclusions can be made about the relationship between stress, psychotropic agents, and male infertility. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Assumption Trade-Offs When Choosing Identification Strategies for Pre-Post Treatment Effect Estimation: An Illustration of a Community-Based Intervention in Madagascar.

PubMed

Weber, Ann M; van der Laan, Mark J; Petersen, Maya L

2015-03-01

Failure (or success) in finding a statistically significant effect of a large-scale intervention may be due to choices made in the evaluation. To highlight the potential limitations and pitfalls of some common identification strategies used for estimating causal effects of community-level interventions, we apply a roadmap for causal inference to a pre-post evaluation of a national nutrition program in Madagascar. Selection into the program was non-random and strongly associated with the pre-treatment (lagged) outcome. Using structural causal models (SCM), directed acyclic graphs (DAGs) and simulated data, we illustrate that an estimand with the outcome defined as the post-treatment outcome controls for confounding by the lagged outcome but not by possible unmeasured confounders. Two separate differencing estimands (of the pre- and post-treatment outcome) have the potential to adjust for a certain type of unmeasured confounding, but introduce bias if the additional identification assumptions they rely on are not met. In order to illustrate the practical impact of choice between three common identification strategies and their corresponding estimands, we used observational data from the community nutrition program in Madagascar to estimate each of these three estimands. Specifically, we estimated the average treatment effect of the program on the community mean nutritional status of children 5 years and under and found that the estimate based on the post-treatment estimand was about a quarter of the magnitude of either of the differencing estimands (0.066 SD vs. 0.26-0.27 SD increase in mean weight-for-age z-score). Choice of estimand clearly has important implications for the interpretation of the success of the program to improve nutritional status of young children. A careful appraisal of the assumptions underlying the causal model is imperative before committing to a statistical model and progressing to estimation. However, knowledge about the data-generating process must be sufficient in order to choose the identification strategy that gets us closest to the truth.

Quantification of the effects of ocean acidification on sediment microbial communities in the environment: the importance of ecosystem approaches.

PubMed

Hassenrück, Christiane; Fink, Artur; Lichtschlag, Anna; Tegetmeyer, Halina E; de Beer, Dirk; Ramette, Alban

2016-05-01

To understand how ocean acidification (OA) influences sediment microbial communities, naturally CO2-rich sites are increasingly being used as OA analogues. However, the characterization of these naturally CO2-rich sites is often limited to OA-related variables, neglecting additional environmental variables that may confound OA effects. Here, we used an extensive array of sediment and bottom water parameters to evaluate pH effects on sediment microbial communities at hydrothermal CO2 seeps in Papua New Guinea. The geochemical composition of the sediment pore water showed variations in the hydrothermal signature at seep sites with comparable pH, allowing the identification of sites that may better represent future OA scenarios. At these sites, we detected a 60% shift in the microbial community composition compared with reference sites, mostly related to increases in Chloroflexi sequences. pH was among the factors significantly, yet not mainly, explaining changes in microbial community composition. pH variation may therefore often not be the primary cause of microbial changes when sampling is done along complex environmental gradients. Thus, we recommend an ecosystem approach when assessing OA effects on sediment microbial communities under natural conditions. This will enable a more reliable quantification of OA effects via a reduction of potential confounding effects. © FEMS 2016.

Independent and combined influence of neonatal and current body composition on academic performance in youth: The UP & DOWN Study.

PubMed

Esteban-Cornejo, I; Tejero-González, C M; Castro-Piñero, J; Conde-Caveda, J; Cabanas-Sanchez, V; Sallis, J F; Veiga, Óscar L

2015-06-01

Unhealthy body composition is a cause for concern across the lifespan. The objective of this study was to examine the independent and combined associations between neonatal and current body composition with academic performance among youth. This cross-sectional study was conducted with a total of 1557 youth (745 girls) aged 10.4 ± 3.4 years. Birth weight and length at birth were self-reported. Current body composition was assessed by body mass index (BMI), waist circumference (WC) and percentage of body fat (BF%). Academic performance was assessed through schools records. Birth weight was related to all academic variables in boys, independent of potential confounders, including BMI; whereas WC, BMI and BF% were related to all academic performance indicators in both boys and girls, independent of potential confounders, including birth weight (all P < 0.05). In addition, the combined adverse effects of low birth weight and current overweight on academic performance were observed in both boys and girls for grade point average (GPA) indicator. Boys in the group with none adverse effect had significantly higher scores in GPA (score +0.535; 95% confidence interval, 0.082-0.989) than boys in the group of both adverse effects (P < 0.007); among girls, GPA score was higher in the group with none adverse effect than in the groups with one or two adverse effects (P for trend = 0.029). Neonatal and current body composition, both independently and combined, may influence academic performance in youth. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

Prenatal depression effects and interventions: a review.

PubMed

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

2010-12-01

This review covers research on the negative effects of prenatal depression and cortisol on fetal growth, prematurity and low birthweight. Although prenatal depression and cortisol were typically measured at around 20 weeks gestation, other research suggests the stability of depression and cortisol levels across pregnancy. Women with Dysthymia as compared to Major Depression Disorder had higher cortisol levels, and their newborns had lower gestational age and birthweight. The cortisol effects in these studies were unfortunately confounded by low serotonin and low dopamine levels which in themselves could contribute to non-optimal pregnancy outcomes. The negative effects of depression and cortisol were also potentially confounded by comorbid anxiety, by demographic factors including younger age, less education and lower SES of the mothers and by the absence of a partner or a partner who was unhappy about the pregnancy or a partner who was depressed. Substance use (especially caffeine use) was still another risk factor. All of these problems including prenatal depression, elevated cortisol, prematurity and low birthweight and even postpartum depression have been reduced by prenatal massage therapy provided by the women's partners. Massage therapy combined with group interpersonal psychotherapy was also effective for reducing depression and cortisol levels. Several limitations of these studies were noted and suggestions for future research included exploring other predictor variables like progesterone/estriol ratios, immune factors and genetic determinants. Further research is needed both on the potential use of cortisol as a screening measure and the use of other therapies that might reduce prenatal depression and cortisol in the women and prematurity and low birthweight in their infants. Copyright © 2010 Elsevier Inc. All rights reserved.

Cellular GFP Toxicity and Immunogenicity: Potential Confounders in in Vivo Cell Tracking Experiments.

PubMed

Ansari, Amir Mehdi; Ahmed, A Karim; Matsangos, Aerielle E; Lay, Frank; Born, Louis J; Marti, Guy; Harmon, John W; Sun, Zhaoli

2016-10-01

Green Fluorescent protein (GFP), used as a cellular tag, provides researchers with a valuable method of measuring gene expression and cell tracking. However, there is evidence to suggest that the immunogenicity and cytotoxicity of GFP potentially confounds the interpretation of in vivo experimental data. Studies have shown that GFP expression can deteriorate over time as GFP tagged cells are prone to death. Therefore, the cells that were originally marked with GFP do not survive and cannot be accurately traced over time. This review will present current evidence for the immunogenicity and cytotoxicity of GFP in in vivo studies by characterizing these responses.

Instrumental Variable Methods for Continuous Outcomes That Accommodate Nonignorable Missing Baseline Values.

PubMed

Ertefaie, Ashkan; Flory, James H; Hennessy, Sean; Small, Dylan S

2017-06-15

Instrumental variable (IV) methods provide unbiased treatment effect estimation in the presence of unmeasured confounders under certain assumptions. To provide valid estimates of treatment effect, treatment effect confounders that are associated with the IV (IV-confounders) must be included in the analysis, and not including observations with missing values may lead to bias. Missing covariate data are particularly problematic when the probability that a value is missing is related to the value itself, which is known as nonignorable missingness. In such cases, imputation-based methods are biased. Using health-care provider preference as an IV method, we propose a 2-step procedure with which to estimate a valid treatment effect in the presence of baseline variables with nonignorable missing values. First, the provider preference IV value is estimated by performing a complete-case analysis using a random-effects model that includes IV-confounders. Second, the treatment effect is estimated using a 2-stage least squares IV approach that excludes IV-confounders with missing values. Simulation results are presented, and the method is applied to an analysis comparing the effects of sulfonylureas versus metformin on body mass index, where the variables baseline body mass index and glycosylated hemoglobin have missing values. Our result supports the association of sulfonylureas with weight gain. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

PubMed

Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

2016-12-01

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

[Somatic consequences of cannabis use].

PubMed

Cottencin, Olivier; Bence, Camille; Rolland, Benjamin; Karila, Laurent

2013-12-01

Cannabis can have negative effects in its users, and a range of acute and chronic health problems associated with cannabis use has been dentified. Acute cannabis consumption is rarely lethal but it is associated with an increased risk of motor vehicle accident because of longer reaction time or impaired motor coordination. Chronic effects of cannabis use include generally cardiovascular and respiratory consequences but there are also oral, gastrointestinal, cutaneous and mucous, metabolic, gynecologic and obstetrical, sexual consequences, and cancer But associated tobacco smoking or other potential confounders may explain part of those somatic consequences.

Gateway Effects: Why the Cited Evidence Does Not Support Their Existence for Low-Risk Tobacco Products (and What Evidence Would).

PubMed

Phillips, Carl V

2015-05-21

It is often claimed that low-risk drugs still create harm because of "gateway effects", in which they cause the use of a high-risk alternative. Such claims are popular among opponents of tobacco harm reduction, claiming that low-risk tobacco products (e.g., e-cigarettes, smokeless tobacco) cause people to start smoking, sometimes backed by empirical studies that ostensibly support the claim. However, these studies consistently ignore the obvious alternative causal pathways, particularly that observed associations might represent causation in the opposite direction (smoking causes people to seek low-risk alternatives) or confounding (the same individual characteristics increase the chance of using any tobacco product). Due to these complications, any useful analysis must deal with simultaneity and confounding by common cause. In practice, existing analyses seem almost as if they were designed to provide teaching examples about drawing simplistic and unsupported causal conclusions from observed associations. The present analysis examines what evidence and research strategies would be needed to empirically detect such a gateway effect, if there were one, explaining key methodological concepts including causation and confounding, examining the logic of the claim, identifying potentially useful data, and debunking common fallacies on both sides of the argument, as well as presenting an extended example of proper empirical testing. The analysis demonstrates that none of the empirical studies to date that are purported to show a gateway effect from tobacco harm reduction products actually does so. The observations and approaches can be generalized to other cases where observed association of individual characteristics in cross-sectional data could result from any of several causal relationships.

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

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

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonitemore » edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites (‘spillover’ effect).« less

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

DOE PAGES

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.; ...

2017-10-06

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonitemore » edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites (‘spillover’ effect).« less

The Role of Objective Numeracy and Fluid Intelligence in Sex-Related Protective Behaviors.

PubMed

Dieckmann, Nathan F; Peters, Ellen; Leon, Juan; Benavides, Martin; Baker, David P; Norris, Alison

2015-01-01

A wealth of studies has indicated that greater cognitive ability is related to healthier behaviors and outcomes throughout the lifespan. In the present paper, we focus on objective numeracy (ability with numbers) and present findings from a study conducted in the Peruvian Highlands that examines the relations among formal education, numeracy, other more general cognitive skills, and a sex-related protective behavior (condom use). Our results show a potential unique protective effect of numeracy on this healthprotective behavior even after accounting for measures of fluid intelligence and potential confounding factors. These results add to a growing literature highlighting the robust protective effect on health behaviors of greater cognitive skills that are enhanced through schooling. Challenges for future research will be identifying the causal mechanisms that underlie these effects and translating this knowledge into effective interventions for improving health.

An education gradient in health, a health gradient in education, or a confounded gradient in both?

PubMed

Lynch, Jamie L; von Hippel, Paul T

2016-04-01

There is a positive gradient associating educational attainment with health, yet the explanation for this gradient is not clear. Does higher education improve health (causation)? Do the healthy become highly educated (selection)? Or do good health and high educational attainment both result from advantages established early in the life course (confounding)? This study evaluates these competing explanations by tracking changes in educational attainment and Self-rated Health (SRH) from age 15 to age 31 in the National Longitudinal Study of Youth, 1997 cohort. Ordinal logistic regression confirms that high-SRH adolescents are more likely to become highly educated. This is partly because adolescent SRH is associated with early advantages including adolescents' academic performance, college plans, and family background (confounding); however, net of these confounders adolescent SRH still predicts adult educational attainment (selection). Fixed-effects longitudinal regression shows that educational attainment has little causal effect on SRH at age 31. Completion of a high school diploma or associate's degree has no effect on SRH, while completion of a bachelor's or graduate degree have effects that, though significant, are quite small (less than 0.1 points on a 5-point scale). While it is possible that educational attainment would have greater effect on health at older ages, at age 31 what we see is a health gradient in education, shaped primarily by selection and confounding rather than by a causal effect of education on health. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effects of own fetal growth on reported hypertension in parous women aged 33.

PubMed

Hennessy, E; Alberman, E

1997-06-01

Data from the study of the British 1958 birth cohort, National Child Development Study (NCDS), has allowed wider investigation of the relationship between retarded fetal growth and risk of adult hypertension. A history of self-reported hypertension was related to fetal growth in 3308 parous cohort members. Fetal growth, the measure used, is the difference in actual birthweight from that expected for the gestational age and subsequent adult height. The relationships were investigated both linearly and non-linearly adjusting for potential confounders. After adjustment for confounding factors, including adult weight for height, retarded fetal growth was associated with reported hypertension particularly when not confined to pregnancy. The latter was also associated with accelerated fetal growth, moderate or severe hypertension in the mother when pregnant with the cohort member, being relatively taller than your mother, and lack of educational qualifications. Hypertension confined to pregnancy was more likely among women who were themselves firstborn or older at childbirth. Neither maternal smoking during cohort's gestation nor cohort member's gestational age had a significant effect. The results are consistent with previous reports that fetal growth effects are less marked if gestation is short. The relationships between fetal growth and subsequent hypertension are extremely complex and variable, and need to be studied allowing for deviations from growth potential. Adult weight for height remains the strongest predictor of hypertension. The results suggest that losing weight is likely to have the same proportional benefit in women with and without a history of retarded fetal growth.

Male circumcision and HIV prevention: current knowledge and future research directions.

PubMed

Bailey, R C; Plummer, F A; Moses, S

2001-11-01

Over the past decade, numerous epidemiological studies have reported a significant association between lack of male circumcision and risk for HIV infection, leading to recommendations for male circumcision to be added to the armamentarium of effective HIV prevention strategies. We review the epidemiological data from studies that have investigated this association, including ecological, cross-sectional/case-control, and prospective studies. We discuss problematic issues in interpreting the epidemiological data, including the presence of other sexually transmitted infections, age of circumcision, and potential confounders such as religion, cultural practices, and genital hygiene. In addition, we review studies of biological mechanisms by which the presence of the foreskin may increase HIV susceptibility, data on risks associated with the circumcision procedure, and available data on the acceptability and feasibility of introducing male circumcision in societies where it is traditionally not practised. Although the evidence in support of male circumcision as an effective HIV prevention measure is compelling, residual confounding in observational studies cannot be excluded. Taken together with concerns over the potential disinhibiting effect of male circumcision on risk behaviour, and safety of the circumcision procedure, randomised trials of male circumcision to prevent HIV infection are recommended. An individual's choice to undergo male circumcision or a community's decision to promote the practice should be made in the light of the best available scientific evidence. More knowledge is required to assist individuals and communities in making those decisions. We conclude with recommendations for future research.

Temporal and spatial influences incur reconfiguration of Arctic heathland soil bacterial community structure.

PubMed

Hill, Richard; Saetnan, Eli R; Scullion, John; Gwynn-Jones, Dylan; Ostle, Nick; Edwards, Arwyn

2016-06-01

Microbial responses to Arctic climate change could radically alter the stability of major stores of soil carbon. However, the sensitivity of plot-scale experiments simulating climate change effects on Arctic heathland soils to potential confounding effects of spatial and temporal changes in soil microbial communities is unknown. Here, the variation in heathland soil bacterial communities at two survey sites in Sweden between spring and summer 2013 and at scales between 0-1 m and, 1-100 m and between sites (> 100 m) were investigated in parallel using 16S rRNA gene T-RFLP and amplicon sequencing. T-RFLP did not reveal spatial structuring of communities at scales < 100 m in any site or season. However, temporal changes were striking. Amplicon sequencing corroborated shifts from r- to K-selected taxon-dominated communities, influencing in silico predictions of functional potential. Network analyses reveal temporal keystone taxa, with a spring betaproteobacterial sub-network centred upon a Burkholderia operational taxonomic unit (OTU) and a reconfiguration to a summer sub-network centred upon an alphaproteobacterial OTU. Although spatial structuring effects may not confound comparison between plot-scale treatments, temporal change is a significant influence. Moreover, the prominence of two temporally exclusive keystone taxa suggests that the stability of Arctic heathland soil bacterial communities could be disproportionally influenced by seasonal perturbations affecting individual taxa. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

The persisting effect of maternal mood in pregnancy on childhood psychopathology.

PubMed

O'Donnell, Kieran J; Glover, Vivette; Barker, Edward D; O'Connor, Thomas G

2014-05-01

Developmental or fetal programming has emerged as a major model for understanding the early and persisting effects of prenatal exposures on the health and development of the child and adult. We leverage the power of a 14-year prospective study to examine the persisting effects of prenatal anxiety, a key candidate in the developmental programming model, on symptoms of behavioral and emotional problems across five occasions of measurement from age 4 to 13 years. The study is based on the Avon Longitudinal Study of Parents and Children cohort, a prospective, longitudinal study of a large community sample in the west of England (n = 7,944). Potential confounders included psychosocial and obstetric risk, postnatal maternal mood, paternal pre- and postnatal mood, and parenting. Results indicated that maternal prenatal anxiety predicted persistently higher behavioral and emotional symptoms across childhood with no diminishment of effect into adolescence. Elevated prenatal anxiety (top 15%) was associated with a twofold increase in risk of a probable child mental disorder, 12.31% compared with 6.83%, after allowing for confounders. Results were similar with prenatal depression. These analyses provide some of the strongest evidence to date that prenatal maternal mood has a direct and persisting effect on her child's psychiatric symptoms and support an in utero programming hypothesis.

Packet Randomized Experiments for Eliminating Classes of Confounders

PubMed Central

Pavela, Greg; Wiener, Howard; Fontaine, Kevin R.; Fields, David A.; Voss, Jameson D.; Allison, David B.

2014-01-01

Background Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design—packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. Methods We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. Results PREs have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. Conclusions Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables. PMID:25444088

Simpson's paradox: A statistician's case study.

PubMed

Chu, Kevin H; Brown, Nathan J; Pelecanos, Anita; Brown, Anthony Ft

2018-02-26

Gender equality and workforce diversity has recently been in the forefront of College discussions. Reasons for the difference between various groups may not be as they initially appeared. The results of comparing the outcome between two groups can sometimes be confounded and even reversed by an unrecognised third variable. This concept is known as Simpson's Paradox, and is illustrated here using a renowned case study on potential gender bias for acceptance to Graduate School at the University of California, Berkeley.  The investigation showed that males were 1.8 times more likely to be admitted to Graduate School than females in 1973. Initially it appeared that women were discriminated against in the selection process. However, when admissions were re-examined at individual Departments of the School, admission tended to be better for women than men in four of six Departments. This contradiction or paradox tells us that the association between admission and gender was dependent upon on Department.  The confounding effect of Department was defined by two characteristics. Firstly, a strong association between Department and admission: some Departments admitted much smaller percentages of applicants than others. Secondly, a strong association between Department and gender: females tended to apply to Departments with lower admission rates.  The explanation of differences between groups can be multifactorial. A search for possible confounders will assist in this understanding. This could apply whenever two groups initially appear to differ, but on closer analysis this difference is either unfounded, or even reversed by reference to a third, confounding variable. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Is the association between posttraumatic stress disorder symptoms and poor health due to a common familial or genetic factor?

PubMed Central

Roy-Byrne, Peter P.; Noonan, Carolyn; Afari, Niloofar; Buchwald, Dedra; Goldberg, Jack

2010-01-01

Objective The objective of this study was to identify genetic, familial and environmental contributions to the association between posttraumatic stress disorder (PTSD) symptoms and poor health. Methods A community sample of 1852 twin pairs was assessed for symptoms of PTSD [with the Impact of Events Scale (IES)] and self-reported global health status using a single five-level question. An ordinal logistic regression model estimated odds ratio/s (OR) for the association between PTSD and health status. Within-pair analysis assessed confounding by familial and genetic factors and adjusted for the possible confounding influence of age, sex, race, education and self-reported physician diagnosis of depression. Results The IES was strongly and significantly associated with self-reported health [OR = 1.8; 95% confidence interval (95% CI) = 1.5–2.2; highest quartile vs. lowest quartile]. This association remained significant in within-pair analysis (OR = 1.3; 95% CI=1.0–1.7), but after further adjustment for sociodemographics and depression, it was no longer significant (Ptrend=.17). Separate analysis by zygosity did not show differential effect in monozygotic or dizygotic pairs. Conclusion These findings suggest that the association between PTSD symptoms and poor health is, in part, due to familial confounding and sociodemographic factors. Little evidence of confounding by genetic factors was found. These findings suggest that early prevention efforts would have the greatest potential for improving poor health in PTSD-prone patients, whereas later intervention efforts directed at treating PTSD may have a more limited impact on improving poor health. PMID:16950376

Age at immigration and crime in Stockholm using sibling comparisons.

PubMed

Beckley, Amber L

2015-09-01

Past Swedish research has shown that immigrants arriving in the receiving country at an older age are less likely to commit crime than immigrants arriving at a younger age. Segmented assimilation theory argues that the family and neighborhood may be important factors affecting how age at immigration and crime are related to one another. This study used population-based register data on foreign-background males from Stockholm to test the effect of age at immigration on crime. Potential confounding from the family and neighborhood was addressed using variables and modeling strategies. Initial results, using variables to control for confounding, showed that people who immigrated around age 4 were the most likely to be suspected of a crime. When controlling for unmeasured family characteristics, it seemed that a later age at immigration was tied to a lower likelihood of crime, which does not corroborate past research findings. The effect of age at immigration, however, was not statistically significant. The results imply that future research on entire families may be a worthwhile endeavor. Copyright © 2015 Elsevier Inc. All rights reserved.

Bayesian propensity scores for high-dimensional causal inference: A comparison of drug-eluting to bare-metal coronary stents.

PubMed

Spertus, Jacob V; Normand, Sharon-Lise T

2018-04-23

High-dimensional data provide many potential confounders that may bolster the plausibility of the ignorability assumption in causal inference problems. Propensity score methods are powerful causal inference tools, which are popular in health care research and are particularly useful for high-dimensional data. Recent interest has surrounded a Bayesian treatment of propensity scores in order to flexibly model the treatment assignment mechanism and summarize posterior quantities while incorporating variance from the treatment model. We discuss methods for Bayesian propensity score analysis of binary treatments, focusing on modern methods for high-dimensional Bayesian regression and the propagation of uncertainty. We introduce a novel and simple estimator for the average treatment effect that capitalizes on conjugacy of the beta and binomial distributions. Through simulations, we show the utility of horseshoe priors and Bayesian additive regression trees paired with our new estimator, while demonstrating the importance of including variance from the treatment regression model. An application to cardiac stent data with almost 500 confounders and 9000 patients illustrates approaches and facilitates comparison with existing alternatives. As measured by a falsifiability endpoint, we improved confounder adjustment compared with past observational research of the same problem. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Midlife work-related stress is associated with late-life cognition.

PubMed

Sindi, Shireen; Kåreholt, Ingemar; Solomon, Alina; Hooshmand, Babak; Soininen, Hilkka; Kivipelto, Miia

2017-09-01

To investigate the associations between midlife work-related stress and late-life cognition in individuals without dementia from the general population. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study population (n = 2000) was randomly selected from independent Finnish population-based surveys (baseline mean age 50 years). Participants underwent two re-examinations in late life (mean age 71 and 78 years, respectively). 1511 subjects participated in at least one re-examination (mean total follow-up 25 years). Work-related stress was measured using two questions on work demands administered in midlife. Multiple cognitive domains were assessed. Analyses were adjusted for several potential confounders. Higher levels of midlife work-related stress were associated with poorer performance on global cognition [β-coefficient, -0.02; 95% confidence interval (CI), -0.05 to -0.00], and processing speed [β -0.03, CI -0.05 to -0.01]. Results remained significant after adjusting for potential confounders. Work-related stress was not significantly associated with episodic memory, executive functioning, verbal fluency or manual dexterity. This study shows that global cognition and processing speed may be particularly susceptible to the effects of midlife work-related stress.

Teacher Quality at the High-School Level: The Importance of Accounting for Tracks. Working Paper 17722. Revised

ERIC Educational Resources Information Center

Jackson, C. Kirabo

2013-01-01

Unlike in elementary school, high-school teacher effects may be confounded with both selection to tracks and unobserved track-level treatments. I document sizable confounding track effects, and show that traditional tests for the existence of teacher effects are likely biased. After accounting for these biases, high-school algebra and English…

Open defecation and childhood stunting in India: an ecological analysis of new data from 112 districts.

PubMed

Spears, Dean; Ghosh, Arabinda; Cumming, Oliver

2013-01-01

Poor sanitation remains a major public health concern linked to several important health outcomes; emerging evidence indicates a link to childhood stunting. In India over half of the population defecates in the open; the prevalence of stunting remains very high. Recently published data on levels of stunting in 112 districts of India provide an opportunity to explore the relationship between levels of open defecation and stunting within this population. We conducted an ecological regression analysis to assess the association between the prevalence of open defecation and stunting after adjustment for potential confounding factors. Data from the 2011 HUNGaMA survey was used for the outcome of interest, stunting; data from the 2011 Indian Census for the same districts was used for the exposure of interest, open defecation. After adjustment for various potential confounding factors--including socio-economic status, maternal education and calorie availability--a 10 percent increase in open defecation was associated with a 0.7 percentage point increase in both stunting and severe stunting. Differences in open defecation can statistically account for 35 to 55 percent of the average difference in stunting between districts identified as low-performing and high-performing in the HUNGaMA data. In addition, using a Monte Carlo simulation, we explored the effect on statistical power of the common practice of dichotomizing continuous height data into binary stunting indicators. Our simulation showed that dichotomization of height sacrifices statistical power, suggesting that our estimate of the association between open defecation and stunting may be a lower bound. Whilst our analysis is ecological and therefore vulnerable to residual confounding, these findings use the most recently collected large-scale data from India to add to a growing body of suggestive evidence for an effect of poor sanitation on human growth. New intervention studies, currently underway, may shed more light on this important issue.

Vegetarian diet and all-cause mortality: Evidence from a large population-based Australian cohort - the 45 and Up Study.

PubMed

Mihrshahi, Seema; Ding, Ding; Gale, Joanne; Allman-Farinelli, Margaret; Banks, Emily; Bauman, Adrian E

2017-04-01

The vegetarian diet is thought to have health benefits including reductions in type 2 diabetes, hypertension, and obesity. Evidence to date suggests that vegetarians tend to have lower mortality rates when compared with non-vegetarians, but most studies are not population-based and other healthy lifestyle factors may have confounded apparent protective effects. The aim of this study was to evaluate the association between categories of vegetarian diet (including complete, semi and pesco-vegetarian) and all-cause mortality in a large population-based Australian cohort. The 45 and Up Study is a cohort study of 267,180 men and women aged ≥45years in New South Wales (NSW), Australia. Vegetarian diet status was assessed by baseline questionnaire and participants were categorized into complete vegetarians, semi-vegetarians (eat meat≤once/week), pesco-vegetarians and regular meat eaters. All-cause mortality was determined by linked registry data to mid-2014. Cox proportional hazards models quantified the association between vegetarian diet and all-cause mortality adjusting for a range of potential confounding factors. Among 243,096 participants (mean age: 62.3years, 46.7% men) there were 16,836 deaths over a mean 6.1years of follow-up. Following extensive adjustment for potential confounding factors there was no significant difference in all-cause mortality for vegetarians versus non-vegetarians [HR=1.16 (95% CI 0.93-1.45)]. There was also no significant difference in mortality risk between pesco-vegetarians [HR=0.79 (95% CI 0.59-1.06)] or semi-vegetarians [HR=1.12 (95% CI 0.96-1.31)] versus regular meat eaters. We found no evidence that following a vegetarian diet, semi-vegetarian diet or a pesco-vegetarian diet has an independent protective effect on all-cause mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Regression approaches in the test-negative study design for assessment of influenza vaccine effectiveness.

PubMed

Bond, H S; Sullivan, S G; Cowling, B J

2016-06-01

Influenza vaccination is the most practical means available for preventing influenza virus infection and is widely used in many countries. Because vaccine components and circulating strains frequently change, it is important to continually monitor vaccine effectiveness (VE). The test-negative design is frequently used to estimate VE. In this design, patients meeting the same clinical case definition are recruited and tested for influenza; those who test positive are the cases and those who test negative form the comparison group. When determining VE in these studies, the typical approach has been to use logistic regression, adjusting for potential confounders. Because vaccine coverage and influenza incidence change throughout the season, time is included among these confounders. While most studies use unconditional logistic regression, adjusting for time, an alternative approach is to use conditional logistic regression, matching on time. Here, we used simulation data to examine the potential for both regression approaches to permit accurate and robust estimates of VE. In situations where vaccine coverage changed during the influenza season, the conditional model and unconditional models adjusting for categorical week and using a spline function for week provided more accurate estimates. We illustrated the two approaches on data from a test-negative study of influenza VE against hospitalization in children in Hong Kong which resulted in the conditional logistic regression model providing the best fit to the data.

Is protective equipment useful in preventing concussion? A systematic review of the literature.

PubMed

Benson, B W; Hamilton, G M; Meeuwisse, W H; McCrory, P; Dvorak, J

2009-05-01

To determine if there is evidence that equipment use reduces sport concussion risk and/or severity. 12 electronic databases were searched using a combination of Medical Subject Headings and text words to identify relevant articles. Specific inclusion and exclusion criteria were used to select studies for review. Data extracted included design, study population, exposure/outcome measures and results. The quality of evidence was assessed based on epidemiologic criteria regarding internal and external validity (ie, strength of design, sample size/power calculation, selection bias, misclassification bias, control of potential confounding and effect modification). In total, 51 studies were selected for review. A comparison between studies was difficult due to the variability in research designs, definition of concussion, mouthguard/helmet/headgear/face shield types, measurements used to assess exposure and outcomes, and variety of sports assessed. The majority of studies were observational, with 23 analytical epidemiologic designs related to the subject area. Selection bias was a concern in the reviewed studies, as was the lack of measurement and control for potentially confounding variables. There is evidence that helmet use reduces head injury risk in skiing, snowboarding and bicycling, but the effect on concussion risk is inconclusive. No strong evidence exists for the use of mouthguards or face shields to reduce concussion risk. Evidence is provided to suggest that full facial protection in ice hockey may reduce concussion severity, as measured by time loss from competition.

Dialyzer Reuse with Peracetic Acid Does Not Impact Patient Mortality

PubMed Central

Bond, T. Christopher; Krishnan, Mahesh; Wilson, Steven M.; Mayne, Tracy

2011-01-01

Summary Background and objectives Numerous studies have shown the overall benefits of dialysis filter reuse, including superior biocompatibility and decreased nonbiodegradable medical waste generation, without increased risk of mortality. A recent study reported that dialyzer reprocessing was associated with decreased patient survival; however, it did not control for sources of potential confounding. We sought to determine the effect of dialyzer reprocessing with peracetic acid on patient mortality using contemporary outcomes data and rigorous analytical techniques. Design, setting, participants, & measurements We conducted a series of analyses of hemodialysis patients examining the effects of reuse on mortality using three techniques to control for potential confounding: instrumental variables, propensity-score matching, and time-dependent survival analysis. Results In the instrumental variables analysis, patients at high reuse centers had 16.2 versus 15.9 deaths/100 patient-years in nonreuse centers. In the propensity-score matched analysis, patients with reuse had a lower death rate per 100 patient-years than those without reuse (15.2 versus 15.5). The risk ratios for the time-dependent survival analyses were 0.993 (per percent of sessions with reuse) and 0.995 (per unit of last reuse), respectively. Over the study period, 13.8 million dialyzers were saved, representing 10,000 metric tons of medical waste. Conclusions Despite the large sample size, powered to detect miniscule effects, neither the instrumental variables nor propensity-matched analyses were statistically significant. The time-dependent survival analysis showed a protective effect of reuse. These data are consistent with the preponderance of evidence showing reuse limits medical waste generation without negatively affecting clinical outcomes. PMID:21566107

Potential Spillover Educational Effects Of Cancer-Related Direct-To-Consumer Advertising On Cancer Patients’ Increased Information Seeking Behaviors: Results From A Cohort Study

PubMed Central

Tan, Andy SL

2014-01-01

Spillover effects of exposure to direct-to-consumer advertising (DTCA) of cancer treatments on patients’ general inquiry about their treatments and managing their illness are not well understood. This study examines the effects of cancer patients’ exposure to cancer-related DTCA on subsequent health information seeking behaviors from clinician and non-clinician sources (lay media and interpersonal contacts). Using a longitudinal survey design over three years, data was collected from cancer survivors diagnosed with colorectal, breast, or prostate cancer who were randomly sampled from the Pennsylvania Cancer Registry. Study outcome measures include patients’ information engagement with their clinicians and information seeking from non-medical sources about cancer treatment and quality of life issues, measured in the second survey. The predictor variable is the frequency of exposure to cancer-related DTCA since diagnosis, measured at the round 1 survey. The analyses utilized lagged weighted multivariate regressions and adjusted for round 1 levels of patient-clinician engagement, information seeking from non-medical sources, and confounders. Exposure to cancer-related DTCA is associated with increased levels of subsequent patient-clinician information engagement (B=.023, 95%CI=.005 to .040, p=.012), controlling for confounders. In comparison, exposure to DTCA is marginally significant in predicting health information seeking from non-clinician sources (B=.009, 95%CI=−.001 to .018, p=.067). Cancer-related DTCA has potentially beneficial spillover effects on health information seeking behaviors among cancer patients. Exposure to DTCA predicts (a little) more patient engagement with their physicians. PMID:24254248

Mediating pathways and gender differences between shift work and subjective cognitive function.

PubMed

Wong, Imelda S; Smith, Peter M; Ibrahim, Selahadin; Mustard, Cameron A; Gignac, Monique A M

2016-11-01

Increased injury risk among shift workers is often attributed to cognitive function deficits that come about as a result of sleep disruptions. However, little is known about the intermediate influences of other factors (eg, work stress, health) which may affect this relationship. In addition, gender differences in these the complex relationships have not been fully explored. The purpose of this study is to (1) identify the extent to which work and non-work factors mediate the relationship between shift work, sleep and subsequent subjective cognitive function; and (2) determine if the mediating pathways differ for men and women. Data from the 2010 National Population Health Survey was used to create a cross-sectional sample of 4255 employed Canadians. Using path modelling, we examined the direct and indirect relationships between shift work, sleep duration, sleep quality and subjective cognitive function. Multigroup analyses tested for significantly different pathways between men and women. Potential confounding effects of age and self-reported health and potential mediating effects of work stress were simultaneously examined. Work stress and sleep quality significantly mediated the effects of shift work on cognition. Age and health confounded the relationship between sleep quality and subjective cognition. No differences were found between men and women. Occupational health and safety programmes are needed to address stress and health factors, in addition to sleep hygiene, to effectively address cognitive function among shift workers. 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/.

Potential spillover educational effects of cancer-related direct-to-consumer advertising on cancer patients' increased information seeking behaviors: results from a cohort study.

PubMed

Tan, Andy S L

2014-06-01

Spillover effects of exposure to direct-to-consumer advertising (DTCA) of cancer treatments on patients' general inquiry about their treatments and managing their illness are not well understood. This study examines the effects of cancer patients' exposure to cancer-related DTCA on subsequent health information seeking behaviors from clinician and non-clinician sources (lay media and interpersonal contacts). Using a longitudinal survey design over 3 years, data was collected from cancer survivors diagnosed with colorectal, breast, or prostate cancer who were randomly sampled from the Pennsylvania Cancer Registry. Study outcome measures include patients' information engagement with their clinicians and information seeking from non-medical sources about cancer treatment and quality of life issues, measured in the second survey. The predictor variable is the frequency of exposure to cancer-related DTCA since diagnosis, measured at the round 1 survey. The analyses utilized lagged-weighted multivariate regressions and adjusted for round 1 levels of patient-clinician engagement, information seeking from nonmedical sources, and confounders. Exposure to cancer-related DTCA is associated with increased levels of subsequent patient-clinician information engagement (B = .023, 95% CI = .005-.040, p = .012), controlling for confounders. In comparison, exposure to DTCA is marginally significant in predicting health information seeking from non-clinician sources (B = .009, 95% CI = -.001-.018, p = .067). Cancer-related DTCA has potentially beneficial spillover effects on health information seeking behaviors among cancer patients. Exposure to DTCA predicts (a little) more patient engagement with their physicians.

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry

PubMed Central

Iqbal, M. Bilal; Robinson, Simon D.; Ding, Lillian; Fung, Anthony; Aymong, Eve; Chan, Albert W.; Hodge, Steven; Della Siega, Anthony; Nadra, Imad J.

2016-01-01

Background Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased. Methods We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods. Results A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis. Conclusions In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data. PMID:26870950

Understanding bias in relationships between the food environment and diet quality: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

PubMed

Rummo, Pasquale E; Guilkey, David K; Ng, Shu Wen; Meyer, Katie A; Popkin, Barry M; Reis, Jared P; Shikany, James M; Gordon-Larsen, Penny

2017-12-01

The relationship between food environment exposures and diet behaviours is unclear, possibly because the majority of studies ignore potential residual confounding. We used 20 years (1985-1986, 1992-1993 2005-2006) of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study across four US cities (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; Oakland, California) and instrumental variables (IV) regression to obtain causal estimates of longitudinal associations between the percentage of neighbourhood food outlets (per total food outlets within 1 km network distance of respondent residence) and an a priori diet quality score, with higher scores indicating higher diet quality. To assess the presence and magnitude of bias related to residual confounding, we compared results from causal models (IV regression) to non-causal models, including ordinary least squares regression, which does not account for residual confounding at all and fixed-effects regression, which only controls for time-invariant unmeasured characteristics. The mean diet quality score across follow-up was 63.4 (SD=12.7). A 10% increase in fast food restaurants (relative to full-service restaurants) was associated with a lower diet quality score over time using IV regression (β=-1.01, 95% CI -1.99 to -0.04); estimates were attenuated using non-causal models. The percentage of neighbourhood convenience and grocery stores (relative to supermarkets) was not associated with diet quality in any model, but estimates from non-causal models were similarly attenuated compared with causal models. Ignoring residual confounding may generate biased estimated effects of neighbourhood food outlets on diet outcomes and may have contributed to weak findings in the food environment literature. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effect of ambient lighting on Laser Doppler Imaging of a standardized cutaneous injury model

PubMed Central

Pham, Alan Chuong Q; Hei, Erik La; Harvey, John G; Holland, Andrew JA

2017-01-01

Objective: The aim of this study was to investigate the potential confounding effects of four different types of ambient lighting on the results of Laser Doppler Imaging (LDI) of a standardized cutaneous injury model. Methods: After applying a mechanical stimulus to the anterior forearm of a healthy volunteer and inducing a wheal and arteriolar flare (the Triple response), we used a Laser Doppler Line Scanner (LDLS) to image the forearm under four different types of ambient lighting: light-emitting-diode (LED), compact fluorescent lighting (CFL), halogen, daylight, and darkness as a control. A spectrometer was used to measure the intensity of light energy at 785 nm, the wavelength used by the scanner for measurement under each type of ambient lighting. Results: Neither the LED nor CFL bulbs emitted detectable light energy at a wavelength of 785 nm. The color-based representation of arbitrary perfusion unit (APU) values of the Triple response measured by the scanner was similar between darkness, LED, and CFL light. Daylight emitted 2 mW at 785 nm, with a slight variation tending more towards lower APU values compared to darkness. Halogen lighting emitted 6 mW of light energy at 785 nm rendering the color-based representation impossible to interpret. Conclusions: Halogen lighting and daylight have the potential to confound results of LDI of cutaneous injuries whereas LED and CFL lighting did not. Any potential sources of daylight should be reduced and halogen lighting completely covered or turned off prior to wound imaging. PMID:29348978

Perceived stress among 20-21 year-olds and their future labour market participation - an eight-year follow-up study.

PubMed

Trolle, Nanna; Lund, Thomas; Winding, Trine Nohr; Labriola, Merete

2017-03-31

Labour market participation among young adults is essential for their future socioeconomic status and health. The aim of this study was to investigate the association between perceived stress among 20-21 year-olds and their labour market participation 8 years later as well as investigate any potential gender differences. A cohort of 1640 young adults born in 1983 completed a questionnaire in 2004 in which perceived stress was measured. The cohort was followed in a register of social benefits for 12 months in 2011-2012 and was categorized into active and passive labour market participation. Logistic regression was used to analyse the association between perceived stress and future labour market participation, taking into account effects of potential confounders. The analyses were stratified by gender. The effects of perceived stress on future labour market participation differed significantly among young women and young men (p = 0.029). For young men, higher levels of perceived stress reduced the risk of future passive labour market participation, when adjusting for socioeconomic factors, self-rated health and copings strategies (p = 0.045). For young women, higher levels of perceived stress increased the risk of future passive labour market participation, when adjusting for the same potential confounding factors, although unlike the men, this association was not statistically significant (p = 0.335). The observed gender difference has important implications from a public health point of view. Healthcare professionals might need to differentiate between the genders in terms of health communication, research and when developing preventive strategies.

Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry.

PubMed

Glintborg, Bente; Sørensen, Inge J; Østergaard, Mikkel; Dreyer, Lene; Mohamoud, Abdiweli A; Krogh, Niels S; Hendricks, Oliver; Andersen, Lis S; Raun, Johnny L; Kowalski, Marcin R; Danielsen, Laura; Pelck, Randi; Nordin, Henrik; Pedersen, Jens K; Kraus, Dorte G A; Christensen, Susan R; Hansen, Inger M J; Esbesen, Jakob; Schlemmer, Annette; Loft, Anne G; Al Chaer, Nabil; Salomonsen, Lone; Hetland, Merete L

2017-01-01

To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status). Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm]. The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27-negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55-84)/65 mm (48-77); global: 76 mm (62-88)/68 mm (50-80); fatigue: 74 mm (55-85)/67 mm (50-80); and BASDAI: 64 (54-77)/59 (46-71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3-17)/11 mg/l (5-22); and BAS Metrology Index: 20 (10-40)/40 (20-50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15-2.02) versus 3.67 years (2.86-4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29-2.36), AS: HR 2.04 (1.53-2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05). In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.

A systematic review and meta-analysis of studies comparing mortality rates of private for-profit and private not-for-profit hospitals

PubMed Central

Devereaux, P.J.; Choi, Peter T.L.; Lacchetti, Christina; Weaver, Bruce; Schünemann, Holger J.; Haines, Ted; Lavis, John N.; Grant, Brydon J.B.; Haslam, David R.S.; Bhandari, Mohit; Sullivan, Terrence; Cook, Deborah J.; Walter, Stephen D.; Meade, Maureen; Khan, Humaira; Bhatnagar, Neera; Guyatt, Gordon H.

2002-01-01

Background Canadians are engaged in an intense debate about the relative merits of private for-profit versus private not-for-profit health care delivery. To inform this debate, we undertook a systematic review and meta-analysis of studies comparing the mortality rates of private for-profit hospitals and those of private not-for-profit hospitals. Methods We identified studies through an electronic search of 11 bibliographical databases, our own files, consultation with experts, reference lists, PubMed and SciSearch. We masked the study results before determining study eligibility. Our eligibility criteria included observational studies or randomized controlled trials that compared private for-profit and private not-for-profit hospitals. We excluded studies that evaluated mortality rates in hospitals with a particular profit status that subsequently converted to the other profit status. For each study, we calculated a relative risk of mortality for private for-profit hospitals relative to private not-for-profit hospitals and pooled the studies of adult populations that included adjustment for potential confounders (e.g., teaching status, severity of illness) using a random effects model. Results Fifteen observational studies, involving more than 26 000 hospitals and 38 million patients, fulfilled the eligibility criteria. In the studies of adult populations, with adjustment for potential confounders, private for-profit hospitals were associated with an increased risk of death (relative risk [RR] 1.020, 95% confidence interval [CI] 1.003–1.038; p = 0.02). The one perinatal study with adjustment for potential confounders also showed an increased risk of death in private for-profit hospitals (RR 1.095, 95% CI 1.050–1.141; p < 0.0001). Interpretation Our meta-analysis suggests that private for-profit ownership of hospitals, in comparison with private not-for-profit ownership, results in a higher risk of death for patients. PMID:12054406

Twins' risk of childhood asthma mediated by gestational age and birthweight.

PubMed

Ullemar, V; Lundholm, C; Almqvist, C

2015-08-01

Children born with low gestational age (GA) or low birthweight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW and have been hypothesized to comprise a high-risk population for asthma. Many previous studies have not accounted for potential confounders or mediators. To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW. The study population consisted of two cohorts including all children born in Sweden from 1 January 1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to 31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birthweight. In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results. Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW, suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding. © 2015 John Wiley & Sons Ltd.

Effectiveness and confounding factors of penetrating astigmatic keratotomy in clinical practice

PubMed Central

Yen, Chu-Yu; Tseng, Gow-Lieng

2018-01-01

Abstract Rationale: Penetrating astigmatic keratotomy (penetrating AK) is a well-known method to correct corneal astigmatism but rarely be performed nowadays. This article reevaluated the clinical effectiveness and confounding factors of penetrating AK. Patient concerns: Penetrating AK has been introduced to serve as one alternative operation for astigmatism correction, and is thought to have the potential advantage of being more affordable and easy to perform. The purpose of our study is to evaluate the effectiveness and confounding factors of penetrating AK. Diagnoses: The chart of 95 patients with corneal astigmatism (range: 0.75–3.25 diopters [D]) who received penetrating AK from January 2014 to December 2016 was collected. The corneal astigmatism were measured by an autokeratometer (Topcon KR8100PA topographer-autorefractor), and repeated with manual keratometer in low reproducibility cases. Interventions: All patients received penetrating AK by an experienced ophthalmologist (Dr. Gow-Lieng Tseng, MD, PHD) in the operation room. Among which, 66 patients received penetrating AK with phacoemulsification simultaneously (group A), whereas 29 patients received penetrating AK at least 3 months after phacoemulsification (group B). After excluding the patients combined with other procedures or lost followed up, 79 patients are remaining for analysis. The outcome was evaluated by net correction, the difference between preoperative corneal astigmatism (PCA) and residual corneal astigmatism (RCA). Two sample t tests and Pearson test were used for effectiveness evaluation. For confounding factors, multivariate linear regression was used for statistical analysis. Outcomes: The mean preoperative and postoperative refractive cylinders were 1.97 ± 0.77 and 1.08 ± 0.64 D, respectively, in group A and 2.62 ± 1.05 and 1.51 ± 0.89 D in group B. There were no statistically significant differences in net correction between these two groups (0.9 ± 0.66 vs. 1.1 ± 0.69, P = .214). Higher PCA were associated with higher net correction in both group A (P = .002) and group B (P = .019). Compound myopic astigmatism caused less net correction than others only in group A (P = 0.031). Lessons: Penetrating AK is an accessible, affordable, and effective way to correct corneal astigmatism. The results of this procedure are comparable to modern methods in patients with low to moderate corneal astigmatism. PMID:29369200

Preconception Maternal Iodine Status Is Positively Associated with IQ but Not with Measures of Executive Function in Childhood.

PubMed

Robinson, Sian M; Crozier, Sarah R; Miles, Elizabeth A; Gale, Catharine R; Calder, Philip C; Cooper, Cyrus; Inskip, Hazel M; Godfrey, Keith M

2018-05-15

Adverse effects of severe maternal iodine deficiency in pregnancy on fetal brain development are well-established, but the effects of milder deficiency are uncertain. Most studies examine iodine status in pregnancy; less is known about iodine nutrition before conception. We examined relations between maternal preconception iodine status and offspring cognitive function, within a prospective mother-offspring cohort. Maternal iodine status was assessed through the use of the ratio of iodine:creatinine concentrations (I/Cr) in spot urine samples [median (IQR) period before conception 3.3 y (2.2-4.7 y)]. Childhood cognitive function was assessed at age 6-7 y. Full-scale IQ was assessed via the Wechsler Abbreviated Scale of Intelligence, and executive function through the use of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses (n = 654 mother-child dyads) were adjusted for potential confounders including maternal intelligence, education, and breastfeeding duration. The median (IQR) urinary iodine concentration was 108.4 µg/L (62.2-167.8 µg/L) and the I/Cr ratio 114 µg/g (76-164 µg/g). The preconception I/Cr ratio was positively associated with child IQ, before and after adjustment for potential confounding influences [β = 0.13 (95% CI: 0.04, 0.21)/SD, P = 0.003]. 8.9% of women had a preconception urinary I/Cr ratio <50 µg/g; compared with those with an I/Cr ratio ≥150 µg/g, the IQ of their offspring was 0.49 (95% CI: 0.79, 0.18) SD lower. There were no associations with the executive function outcomes assessed via CANTAB, before or after adjustment for confounders. The positive association between iodine status before conception and child IQ provides some support for demonstrated links between low maternal iodine status in pregnancy and poorer cognitive function reported in other studies. However, given the negative effects on school performance previously observed in children born to iodine-deficient mothers, the lack of associations with measures of executive function in the present study was unexpected. Further data are needed to establish the public health importance of low preconception iodine status.

External radiation dose and cancer mortality among French nuclear workers: considering potential confounding by internal radiation exposure.

PubMed

Fournier, L; Laurent, O; Samson, E; Caër-Lorho, S; Laroche, P; Le Guen, B; Laurier, D; Leuraud, K

2016-11-01

French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat à l'Energie Atomique), AREVA NC, or EDF (Electricité de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination.

Clinical Research Methodology 2: Observational Clinical Research.

PubMed

Sessler, Daniel I; Imrey, Peter B

2015-10-01

Case-control and cohort studies are invaluable research tools and provide the strongest feasible research designs for addressing some questions. Case-control studies usually involve retrospective data collection. Cohort studies can involve retrospective, ambidirectional, or prospective data collection. Observational studies are subject to errors attributable to selection bias, confounding, measurement bias, and reverse causation-in addition to errors of chance. Confounding can be statistically controlled to the extent that potential factors are known and accurately measured, but, in practice, bias and unknown confounders usually remain additional potential sources of error, often of unknown magnitude and clinical impact. Causality-the most clinically useful relation between exposure and outcome-can rarely be definitively determined from observational studies because intentional, controlled manipulations of exposures are not involved. In this article, we review several types of observational clinical research: case series, comparative case-control and cohort studies, and hybrid designs in which case-control analyses are performed on selected members of cohorts. We also discuss the analytic issues that arise when groups to be compared in an observational study, such as patients receiving different therapies, are not comparable in other respects.

Toxicity of the molybdate anion in soil is partially explained by effects of the accompanying cation or by soil pH.

PubMed

Buekers, Jurgen; Mertens, Jelle; Smolders, Erik

2010-06-01

Previous studies have shown that toxicity of cationic trace metals in soil is partially confounded by effects of the accompanying anions. A similar assessment is reported here for toxicity of an oxyanion, i.e., molybdate (MoO(4) (2-)), the soil toxicity of which is relatively unexplored. Solubility and toxicity were compared between the soluble sodium molybdate (Na(2)MoO(4)) and the sparingly soluble molybdenum trioxide (MoO(3)). Confounding effects of salinity were excluded by referencing the Na(2)MoO(4) effect to that of sodium chloride (NaCl). The pH decrease from the acid MoO(3) amendment was equally referenced to a hydrochloric (HCl) treatment or a lime-controlled MoO(3) treatment. The concentrations of molybdenum (Mo) in soil solution or calcium chloride (CaCl(2)) 0.01 M extracts were only marginally affected by either MoO(3) or Na(2)MoO(4) as an Mo source after 10 to 13 days of equilibration. Effects of Mo on soil nitrification were fully confounded by associated changes in salinity or pH. Effects of Mo on growth of wheat seedlings (Triticum aestivum L) were more pronounced than those on nitrification, and toxicity thresholds were unaffected by the form of added Mo. The Mo thresholds for wheat growth were not confounded by pH or salinity at incipient toxicity. It is concluded that oxyanion toxicity might be confounded in relatively insensitive tests for which reference treatments should be included. Copyright 2010 SETAC.

Increased Mortality in Groups of Cattle Administered the β-Adrenergic Agonists Ractopamine Hydrochloride and Zilpaterol Hydrochloride

PubMed Central

Loneragan, Guy H.; Thomson, Daniel U.; Scott, H. Morgan

2014-01-01

The United States Food and Drug Administration (FDA) approved two β-adrenergic agonists (βAA) for in-feed administration to cattle fed in confinement for human consumption. Anecdotal reports have generated concern that administration of βAA might be associated with an increased incidence of cattle deaths. Our objectives, therefore, were to a) quantify the association between βAA administration and mortality in feedlot cattle, and b) explore those variables that may confound or modify this association. Three datasets were acquired for analysis: one included information from randomized and controlled clinical trials of the βAA ractopamine hydrochloride, while the other two were observational data on zilpaterol hydrochloride administration to large numbers of cattle housed, fed, and cared for using routine commercial production practices in the U.S. Various population and time at-risk models were developed to explore potential βAA relationships with mortality, as well as the extent of confounding and effect modification. Measures of effect were relatively consistent across datasets and models in that the cumulative risk and incidence rate of death was 75 to 90% greater in animals administered the βAA compared to contemporaneous controls. During the exposure period, 40 to 50% of deaths among groups administered the βAA were attributed to administration of the drug. None of the available covariates meaningfully confounded the relationship between βAA and increased mortality. Only month of slaughter, presumably a proxy for climate, consistently modified the effect in that the biological association was generally greatest during the warmer months of the year. While death is a rare event in feedlot cattle, the data reported herein provide compelling evidence that mortality is nevertheless increased in response to administration of FDA-approved βAA and represents a heretofore unquantified adverse drug event. PMID:24621596

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.

Gateway Effects: Why the Cited Evidence Does Not Support Their Existence for Low-Risk Tobacco Products (and What Evidence Would)

PubMed Central

Phillips, Carl V.

2015-01-01

It is often claimed that low-risk drugs still create harm because of “gateway effects”, in which they cause the use of a high-risk alternative. Such claims are popular among opponents of tobacco harm reduction, claiming that low-risk tobacco products (e.g., e-cigarettes, smokeless tobacco) cause people to start smoking, sometimes backed by empirical studies that ostensibly support the claim. However, these studies consistently ignore the obvious alternative causal pathways, particularly that observed associations might represent causation in the opposite direction (smoking causes people to seek low-risk alternatives) or confounding (the same individual characteristics increase the chance of using any tobacco product). Due to these complications, any useful analysis must deal with simultaneity and confounding by common cause. In practice, existing analyses seem almost as if they were designed to provide teaching examples about drawing simplistic and unsupported causal conclusions from observed associations. The present analysis examines what evidence and research strategies would be needed to empirically detect such a gateway effect, if there were one, explaining key methodological concepts including causation and confounding, examining the logic of the claim, identifying potentially useful data, and debunking common fallacies on both sides of the argument, as well as presenting an extended example of proper empirical testing. The analysis demonstrates that none of the empirical studies to date that are purported to show a gateway effect from tobacco harm reduction products actually does so. The observations and approaches can be generalized to other cases where observed association of individual characteristics in cross-sectional data could result from any of several causal relationships. PMID:26006122

Quasi-experimental study designs series-paper 10: synthesizing evidence for effects collected from quasi-experimental studies presents surmountable challenges.

PubMed

Becker, Betsy Jane; Aloe, Ariel M; Duvendack, Maren; Stanley, T D; Valentine, Jeffrey C; Fretheim, Atle; Tugwell, Peter

2017-09-01

To outline issues of importance to analytic approaches to the synthesis of quasi-experiments (QEs) and to provide a statistical model for use in analysis. We drew on studies of statistics, epidemiology, and social-science methodology to outline methods for synthesis of QE studies. The design and conduct of QEs, effect sizes from QEs, and moderator variables for the analysis of those effect sizes were discussed. Biases, confounding, design complexities, and comparisons across designs offer serious challenges to syntheses of QEs. Key components of meta-analyses of QEs were identified, including the aspects of QE study design to be coded and analyzed. Of utmost importance are the design and statistical controls implemented in the QEs. Such controls and any potential sources of bias and confounding must be modeled in analyses, along with aspects of the interventions and populations studied. Because of such controls, effect sizes from QEs are more complex than those from randomized experiments. A statistical meta-regression model that incorporates important features of the QEs under review was presented. Meta-analyses of QEs provide particular challenges, but thorough coding of intervention characteristics and study methods, along with careful analysis, should allow for sound inferences. Copyright © 2017 Elsevier Inc. All rights reserved.

Bilingualism delays age at onset of dementia, independent of education and immigration status.

PubMed

Alladi, Suvarna; Bak, Thomas H; Duggirala, Vasanta; Surampudi, Bapiraju; Shailaja, Mekala; Shukla, Anuj Kumar; Chaudhuri, Jaydip Ray; Kaul, Subhash

2013-11-26

The purpose of the study was to determine the association between bilingualism and age at onset of dementia and its subtypes, taking into account potential confounding factors. Case records of 648 patients with dementia (391 of them bilingual) diagnosed in a specialist clinic were reviewed. The age at onset of first symptoms was compared between monolingual and bilingual groups. The influence of number of languages spoken, education, occupation, and other potentially interacting variables was examined. Overall, bilingual patients developed dementia 4.5 years later than the monolingual ones. A significant difference in age at onset was found across Alzheimer disease dementia as well as frontotemporal dementia and vascular dementia, and was also observed in illiterate patients. There was no additional benefit to speaking more than 2 languages. The bilingual effect on age at dementia onset was shown independently of other potential confounding factors such as education, sex, occupation, and urban vs rural dwelling of subjects. This is the largest study so far documenting a delayed onset of dementia in bilingual patients and the first one to show it separately in different dementia subtypes. It is the first study reporting a bilingual advantage in those who are illiterate, suggesting that education is not a sufficient explanation for the observed difference. The findings are interpreted in the context of the bilingual advantages in attention and executive functions.

Associations of work stress with hair cortisol concentrations - initial findings from a prospective study.

PubMed

Herr, Raphael M; Almer, Christian; Loerbroks, Adrian; Barrech, Amira; Elfantel, Irina; Siegrist, Johannes; Gündel, Harald; Angerer, Peter; Li, Jian

2018-03-01

There is ample evidence supporting the link between stress at the workplace and physical and mental health. One of the pathways potentially mediating those associations may involve the hypothalamic-pituitary-adrenal (HPA) axis, with cortisol as an end product. While theoretically plausible, findings on the association of self-reported work stress with hair cortisol concentrations (HCC) are inconclusive, being potentially biased by omitted pertinent factors. This issue can be addressed, among others, by eliminating time-invariant factors through consideration of variation within persons over time. To this end, the present study examined the association between variation in HCC and perceived work stress - as assessed by the Effort-Reward-Imbalance (ERI) model - between two points in time (t1 and t2) over one year in a sample of 40 male factory workers. Neither a cross-sectional association, nor a link between change in ERI and HCC levels at t2 was observed. There was however a robust association of the change in ERI with the change of HCC. This effect was independent of baseline HCC and other confounders (Beta = 0.414, S.E. = 0.155, p = 0.012). Accordingly, this is the first study revealing prospective evidence for the associations of work stress with HCC, while excluding potentially time-stable confounding factors, like genetic factors or phenotypic hair color. Copyright © 2018 Elsevier Ltd. All rights reserved.

Major depressive disorder and impulsive reactivity to emotion: toward a dual-process view of depression.

PubMed

Carver, Charles S; Johnson, Sheri L; Joormann, Jutta

2013-09-01

Dual-process theories of behaviour have been used to suggest that vulnerability to depression involves elevated reactivity to emotions. This study tests that idea, examining self-reported reactivity. Comparison between persons with at least one lifetime episode of major depressive disorder (lifetime MDD) and those without this diagnosis, controlling for symptoms of alcohol use (a potential externalizing confound) and current symptoms of depression (a potential state-dependent confound). Undergraduates (N = 120) completed a clinical interview to diagnose lifetime MDD and a series of self-reports bearing on diverse aspects of self-control, including reactivity to emotion. Thirty-four people were diagnosed with lifetime MDD; 86 did not meet criteria for MDD. The groups were then compared on three factors underlying the scales assessing self-control. The MDD group had higher scores than controls on the two factors that reflect impulsive reactivity to diverse emotions, including emotions that are positive in valence. These effects were not explained by associations with either externalizing symptoms or current depressive symptoms. Reflexive reactivity to emotions characterizes depression, in addition to some externalizing problems, and it may deserve study as a potential trans-diagnostic feature. Reflexive reactivity to emotions characterizes persons diagnosed with major depressive disorder. Findings suggest desirability of focusing treatment partly on management of reflexive reactions to emotions. Measures were self-reports, rather than behavioural responses to emotions. © 2013 The British Psychological Society.

Association between borderline dysnatremia and mortality insight into a new data mining approach.

PubMed

Girardeau, Yannick; Jannot, Anne-Sophie; Chatellier, Gilles; Saint-Jean, Olivier

2017-11-22

Even small variations of serum sodium concentration may be associated with mortality. Our objective was to confirm the impact of borderline dysnatremia for patients admitted to hospital on in-hospital mortality using real life care data from our electronic health record (EHR) and a phenome-wide association analysis (PheWAS). Retrospective observational study based on patient data admitted to Hôpital Européen George Pompidou, between 01/01/2008 and 31/06/2014; including 45,834 patients with serum sodium determinations on admission. We analyzed the association between dysnatremia and in-hospital mortality, using a multivariate logistic regression model to adjust for classical potential confounders. We performed a PheWAS to identify new potential confounders. Hyponatremia and hypernatremia were recorded for 12.0% and 1.0% of hospital stays, respectively. Adjusted odds ratios (ORa) for severe, moderate and borderline hyponatremia were 3.44 (95% CI, 2.41-4.86), 2.48 (95% CI, 1.96-3.13) and 1.98 (95% CI, 1.73-2.28), respectively. ORa for severe, moderate and borderline hypernatremia were 4.07 (95% CI, 2.92-5.62), 4.42 (95% CI, 2.04-9.20) and 3.72 (95% CI, 1.53-8.45), respectively. Borderline hyponatremia (ORa = 1.57 95% CI, 1.35-1.81) and borderline hypernatremia (ORa = 3.47 95% CI, 2.43-4.90) were still associated with in-hospital mortality after adjustment for classical and new confounding factors identified through the PheWAS analysis. Borderline dysnatremia on admission are independently associated with a higher risk of in-hospital mortality. By using medical data automatically collected in EHR and a new data mining approach, we identified new potential confounding factors that were highly associated with both mortality and dysnatremia.

Interaction effect of job insecurity and role ambiguity on psychological distress in Japanese employees: a cross-sectional study.

PubMed

Inoue, Akiomi; Kawakami, Norito; Eguchi, Hisashi; Tsutsumi, Akizumi

2018-05-01

We examined the interaction effect of job insecurity (JI) and role ambiguity (RA) on psychological distress in Japanese employees. Overall, 2184 male and 805 female employees from two factories of a manufacturing company in Japan completed a self-administered questionnaire comprising the scales measuring JI (Job Content Questionnaire), RA (National Institute for Occupational Safety and Health Generic Job Stress Questionnaire), psychological distress (K6 scale), and potential confounders (i.e., age, education, family size, occupational class, and work shift). Taking psychological distress as a dependent variable, hierarchical multiple regression analyses were conducted by gender and employment status (i.e., permanent and non-permanent employees). An interaction term of JI × RA was included in the model. After adjusting for potential confounders, the main effects of JI and RA on psychological distress were significant regardless of gender or employment status. Furthermore, the significant interaction effect of JI × RA on psychological distress was observed among permanent male employees (β = 0.053, p = 0.010). Post hoc simple slope analyses showed that the simple slope of JI was greater at higher levels of RA (i.e., one standard deviation [SD] above the mean) (β = 0.300, p < 0.001) compared to lower levels of RA (i.e., one SD below the mean) (β = 0.212, p < 0.001). On the other hand, the interaction effect of JI × RA was not significant among permanent or non-permanent female employees. The present study suggests that higher levels of RA strengthen the association of JI with psychological distress, at least among Japanese permanent male employees.

Breastfeeding is positively associated with child intelligence even net of parental IQ.

PubMed

Kanazawa, Satoshi

2015-12-01

Some previous reviews conclude that breastfeeding is not significantly associated with increased intelligence in children once mother's IQ is statistically controlled. The conclusion may potentially have both theoretical and methodological problems. The National Child Development Study allows the examination of the effect of breastfeeding on intelligence in two consecutive generations of British children. The analysis of the first generation shows that the effect of breastfeeding on intelligence increases from Age 7 to 16. The analysis of the second generation shows that each month of breastfeeding, net of parental IQ and other potential confounds, is associated with an increase of .16 IQ points. Further analyses suggest that some previous studies may have failed to uncover the effect of breastfeeding on child intelligence because of their reliance on one IQ test. (c) 2015 APA, all rights reserved).

Cannabis use disorder is associated with greater illness severity in tobacco smoking patients with bipolar disorder.

PubMed

Lagerberg, T V; Icick, R; Andreassen, O A; Ringen, P A; Etain, B; Aas, M; Henry, C; Bjella, T D; Melle, I; Bellivier, F

2016-01-15

Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients. A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses. In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant. Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for. Studies have found associations between tobacco smoking and poorer outcomes in BD. In this study on tobacco smoking BD patients we report an association between CUD and illness severity, suggesting that CUD exacerbates the disease evolution independently of tobacco smoking. Specific treatment and prevention programs addressing CUD in BD patients are warranted. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of pH and temperature on optical rotatory dispersion for noninvasive glucose monitoring

NASA Astrophysics Data System (ADS)

Baba, Justin S.; Meledeo, Adam; Cameron, B. D.; Cote, Gerard L.

2001-06-01

The widespread occurrence of diabetes mellitus and the severity of its associated complications necessitate the development of non-invasive blood glucose measurement devices in an attempt to improve treatment regimens and curb the complications associated with this disease. One method showing promise in this endeavor utilizes optical polarimetry to monitor blood glucose levels indirectly by measuring glucose rotation of polarized light, which is a direct indication of glucose concentration, in the aqueous humor of the eye. The presence of other optically active (chiral) components in the aqueous humor of the eye have the potential to confound the glucose measurement of optical rotation when using a single wavelength polarimeter. Thus, this has led to the recent investigation of multispectral polarimetric systems which have the potential to enable the removal of confounder contributions to the net observed optical rotation, therefore, increasing glucose specificity and reducing glucose prediction errors. Such polarimetric systems take advantage of the uniqueness in the rotation of polarized light, as a function of wavelength, by the chiral molecule of interest. This is commonly referred to as the optical rotatory dispersion (ORD) spectra of the chiral molecule. ORD characterization of the chiral molecules within the aqueous humor is necessary for determining the optimum number of wavelengths needed to reduce glucose prediction errors; however, this information is often only given at the sodium-D line (589 nm) in the literature. This report describes the system we designed and built to measure ORD spectra for glucose and for albumin, the main optical confounder within the aqueous humor, as well as our investigation of the effects of temperature and pH on these ORD spectra.

Intelligence and all-cause mortality in the 6-Day Sample of the Scottish Mental Survey 1947 and their siblings: testing the contribution of family background.

PubMed

Iveson, Matthew H; Cukic, Iva; Der, Geoff; Batty, G David; Deary, Ian J

2018-02-01

Higher early-life intelligence is associated with a reduced risk of mortality in adulthood, though this association is apparently hardly attenuated when accounting for early-life socio-economic status (SES). However, the use of proxy measures of SES means that residual confounding may underestimate this attenuation. In the present study, the potential confounding effect of early-life SES was instead accounted for by examining the intelligence-mortality association within families. The association between early-life intelligence and mortality in adulthood was assessed in 727 members of the 6-Day Sample of the Scottish Mental Survey 1947 and, for the first time, 1580 of their younger siblings. These individuals were born between 1936 and 1958, and were followed up into later life, with deaths recorded up to 2015. Cox regression was used to estimate the relative risk of mortality associated with higher IQ scores after adjusting for shared family factors. A standard-deviation advantage in IQ score was associated with a significantly reduced mortality risk [hazard ratio = 0.76, p < 0.001, 95% confidence interval (CI) (0.68-0.84)]. This reduction in hazard was only slightly attenuated by adjusting for sex and shared family factors [hazard ratio = 0.79, p = 0.002, 95% CI (0.68-0.92)]. Although somewhat conservative, adjusting for all variance shared by a family avoids any potential residual confounding of the intelligence-mortality association arising from the use of proxy measures of early-life SES. The present study demonstrates that the longevity associated with higher early-life intelligence cannot be explained by early-life SES or within-family factors. © The Author 2017; Published by Oxford University Press on behalf of the International Epidemiological Association

Identification of Effects of Regulatory Actions on Air Quality in Goods Movement Corridors in California.

PubMed

Su, Jason G; Meng, Ying-Ying; Pickett, Melissa; Seto, Edmund; Ritz, Beate; Jerrett, Michael

2016-08-16

Few studies have assessed the impact of regulatory actions on air quality improvement through a comprehensive monitoring effort. In this study, we designed saturation sampling of nitrogen oxides (NOX) for the counties of Los Angeles and Alameda (San Francisco Bay) before (2003-2007) and after (2008-2013) implementation of goods movement actions in California. We further separated the research regions into three location categories, including goods movement corridors (GMCs), nongoods movement corridors (NGMCs), and control areas (CTRLs). Linear mixed models were developed to identify whether reductions in NOX were greater in GMCs than in other areas, after controlling for potential confounding, including weather conditions (e.g., wind speed and temperature) and season of sampling. We also considered factors that might confound the relationship, including traffic and cargo volumes that may have changed due to economic downturn impacts. Compared to the pre-policy period, we found reductions of average pollutant concentrations for nitrogen dioxide (NO2) and NOX in GMCs of 6.4 and 21.7 ppb. The reductions were smaller in NGMCs (5.9 and 16.3 ppb, respectively) and in CTRLs (4.6 and 12.1 ppb, respectively). After controlling for potential confounding from weather conditions, season of sampling, and the economic downturn in 2008, the linear mixed models demonstrated that reductions in NO2 and NOX were significantly greater in GMCs compared to reductions observed in CTRLs; there were no statistically significant differences between NGMCs and CTRLs. These results indicate that policies regulating goods movement are achieving the desired outcome of improving air quality for the state, particularly in goods movement corridors where most disadvantaged communities live.

Risk of Breast Cancer Associated with Reproductive and Fertility Factors According to a Family History of Breast Cancer

DTIC Science & Technology

1999-10-01

also ruled out as confounders. Polycystic ovaries and endometriosis, possible indications for using OCs, were evaluated as potential confounders, but...Cn polymorphism In the MTHFR gone with breast and/or A irne genomic deletion of hMLHI in a family with Muir-Torre syndrome . J.J.P.canoer risk In...reduion I te,1Teth-A Muir-Torre syndrome (MTS) is an autosomal dominant condition characterized by se- Miylonetetrathydrofoiate reductase (MTHFR

The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice

PubMed Central

Ingvorsen, C; Karp, N A; Lelliott, C J

2017-01-01

Background: Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. Methods: We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. Results: HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. Conclusion: HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes. PMID:28394359

Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report--Part II.

PubMed

Cox, Emily; Martin, Bradley C; Van Staa, Tjeerd; Garbe, Edeltraut; Siebert, Uwe; Johnson, Michael L

2009-01-01

The goal of comparative effectiveness analysis is to examine the relationship between two variables, treatment, or exposure and effectiveness or outcome. Unlike data obtained through randomized controlled trials, researchers face greater challenges with causal inference with observational studies. Recognizing these challenges, a task force was formed to develop a guidance document on methodological approaches to addresses these biases. The task force was commissioned and a Chair was selected by the International Society for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007. This report, the second of three reported in this issue of the Journal, discusses the inherent biases when using secondary data sources for comparative effectiveness analysis and provides methodological recommendations to help mitigate these biases. The task force report provides recommendations and tools for researchers to mitigate threats to validity from bias and confounding in measurement of exposure and outcome. Recommendations on design of study included: the need for data analysis plan with causal diagrams; detailed attention to classification bias in definition of exposure and clinical outcome; careful and appropriate use of restriction; extreme care to identify and control for confounding factors, including time-dependent confounding. Design of nonrandomized studies of comparative effectiveness face several daunting issues, including measurement of exposure and outcome challenged by misclassification and confounding. Use of causal diagrams and restriction are two techniques that can improve the theoretical basis for analyzing treatment effects in study populations of more homogeneity, with reduced loss of generalizability.

Adrenergic blockers and the risk for common solid cancers: a case-control study.

PubMed

Numbere, Beade; Fleming, Kate M; Walker, Alex; Card, Timothy R

2017-01-01

Laboratory studies have suggested that adrenergic blockers may inhibit the proliferation and migration of cancer cells, but epidemiological evidence of their effect on cancer incidence has proven inconsistent. We therefore conducted a case-control study using the Clinical Practice Research Datalink to assess the effect of adrenergic blockers on the incidence of prostate, lung, bowel and breast cancers. From among patients aged 18 years or older who contributed at least 2 years of prospectively gathered data between 1 January 1987 and 31 December 2012, we selected incident cases of relevant cancers and controls, frequency matched 10 : 1 by age. Logistic regression was used to adjust effect estimates for age, sex, smoking, alcohol use, and a number of potentially confounding comorbidities and coprescriptions. A total of 18 968 colorectal, 19 082 lung, 21 608 prostate and 29 109 breast cancers were identified. We found no evidence of a protective effect of adrenergic blockade in lung and prostate cancers and found a slightly increased risk for colorectal and breast cancers in users. This was largely explained by the effects of confounding in multivariate analyses, with final odds ratio estimates for lung, colorectal, breast and prostate cancers of 0.99 [95% confidence interval (0.96-1.04)], 1.14 (1.09-1.18), 1.10 (1.06-1.14), and 1.01 (0.98-1.05), respectively, for β-blocker exposure, and final odds ratio estimates for lung, colorectal and breast cancer of 1.03 (0.97-1.09), 1.13 (1.07-1.20), and 1.08 (1.00-1.17), respectively, for α-blocker exposure. We found no evidence to suggest that adrenergic blocker use prevents common cancers. Indeed, we found a slightly increased risk for colorectal and breast cancers, which may reflect residual confounding.

Occupational exposure and ovarian cancer risk.

PubMed

Le, Nhu D; Leung, Andy; Brooks-Wilson, Angela; Gallagher, Richard P; Swenerton, Kenneth D; Demers, Paul A; Cook, Linda S

2014-07-01

Relatively little work has been done concerning occupational risk factors in ovarian cancer. Although studies conducted in occupational settings have reported positive associations, their usefulness is generally limited by the lack of information on important confounders. In a population-based case-control study, we assessed risk for developing epithelial ovarian cancer (EOC) associated with occupational exposure while accounting for important confounders. Participants were identified through provincial population-based registries. Lifetime occupational history and information on potential confounding factors were obtained through a self-administered questionnaire. Unconditional logistic regression and the likelihood ratio test were used to assess EOC risk with each occupation (or industry), relative to all other occupations (or industries), adjusting for potential confounders including body mass index, oral contraceptive use, menopausal hormone therapy, parity, age at first childbirth, age at menarche, age at menopause, family history of breast and ovarian cancer in mother and sister(s), tubal ligation, partial oophorectomy, and hysterectomy. Occupations and industries were coded according to the Canadian Standard Occupational Classification (SOC) and Standard Industrial Classification (SIC). Significant excess risk was observed for several groups of teaching occupations, including SOC 27, teaching and related (adjusted OR 1.77, 95% CI 1.15-2.81) and SOC 279, other teaching and related (adjusted OR 3.11, 95% CI 1.35-8.49). Significant excess was also seen for a four-digit occupational group SOC 4131, bookkeepers and accounting clerks (adjusted OR 2.80, 95% CI 1.30-6.80). Industrial sub-groups showing significant excess risk included SIC 65, other retail stores (adjusted OR 2.19, 95 % CI 1.16-4.38); SIC 85, educational service (adjusted OR 1.45, 95% CI 1.00-2.13); and SIC 863, non-institutional health services (adjusted OR 2.54, 95% CI 1.13-6.52). Our study found an elevated EOC risk for teaching occupations and is the first study to observe such an increased risk after adjustment for potential confounders. Further studies with more detailed assessment of the work environment and unique lifestyle characteristics may be fruitful in elucidating this etiology.

Leveraging Hierarchical Population Structure in Discrete Association Studies

PubMed Central

Carlson, Jonathan; Kadie, Carl; Mallal, Simon; Heckerman, David

2007-01-01

Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in Arabidopsis thaliana. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding. Analysis tools based on these models are available on the internet as both web based applications and downloadable source code at http://atom.research.microsoft.com/bio/phylod.aspx. PMID:17611623

Divergent marijuana trajectories among men: Socioeconomic, relationship, and life satisfaction outcomes in the mid-30s

PubMed Central

White, Helene R.; Bechtold, Jordan; Loeber, Rolf; Pardini, Dustin

2016-01-01

Background Given recent changes in marijuana policy in the United States, it is important to understand the long-term effects of marijuana use on adult functioning. We examined whether men who displayed different trajectories of marijuana use from adolescence through emerging adulthood (age ~15–26) differed in terms of socioeconomic, social, and life satisfaction outcomes in their mid-30s. Methods Data came from a longitudinal sample of men who were recruited in early adolescence (N = 506) and followed into adulthood. Four trajectory groups based on patterns of marijuana use from adolescence into emerging adulthood were compared on adult outcomes (age ~36) before and after controlling for co-occurring use of other substances and several pre-existing confounding factors in early adolescence. The potential moderating effect of race was also examined. Results Although there were initially group differences across all domains, once pre-existing confounds and co-occurring other substance use were included in the model, groups only differed in terms of partner and friend marijuana use. Chronic marijuana users reported the highest proportions of both. Frequent and persistent marijuana use was associated with lower socioeconomic status (SES) for Black men only. Conclusions After statistically accounting for confounding variables, chronic marijuana users were not at a heightened risk for maladjustment in adulthood except for lower SES among Black men. Chronic users were more likely to have friends and partners who also used marijuana. Future studies should take into account pre-existing differences when examining outcomes of marijuana use. PMID:26365837

Assessing health system interventions: key points when considering the value of randomization

PubMed Central

Schellenberg, Joanna; Todd, Jim

2011-01-01

Abstract Research is needed to help identify interventions that will improve the capacity or functioning of health systems and thereby contribute to achieving global health goals. Well conducted, randomized controlled trials (RCTs), insofar as they reduce bias and confounding, provide the strongest evidence for identifying which interventions delivered directly to individuals are safe and effective. When ethically feasible, they can also help reduce bias and confounding when assessing interventions targeting entire health systems. However, additional challenges emerge when research focuses on interventions that target the multiple units of organization found within health systems. Hence, one cannot complacently assume that randomization can reduce or eliminate bias and confounding to the same degree in every instance. While others have articulated arguments in favour of alternative designs, this paper is intended to help people understand why the potential value afforded by RCTs may be threatened. Specifically, it suggests six points to be borne in mind when exploring the challenges entailed in designing or evaluating RCTs on health system interventions: (i) the number of units available for randomization; (ii) the complexity of the organizational unit under study; (iii) the complexity of the intervention; (iv) the complexity of the cause–effect pathway, (v) contamination; and (vi) outcome heterogeneity. The authors suggest that the latter may be informative and that the reasons behind it should be explored and not ignored. Based on improved understanding of the value and possible limitations of RCTs on health system interventions, the authors show why we need broader platforms of research to complement RCTs. PMID:22271948

Factors influencing tests of auditory processing: a perspective on current issues and relevant concerns.

PubMed

Cacace, Anthony T; McFarland, Dennis J

2013-01-01

Tests of auditory perception, such as those used in the assessment of central auditory processing disorders ([C]APDs), represent a domain in audiological assessment where measurement of this theoretical construct is often confounded by nonauditory abilities due to methodological shortcomings. These confounds include the effects of cognitive variables such as memory and attention and suboptimal testing paradigms, including the use of verbal reproduction as a form of response selection. We argue that these factors need to be controlled more carefully and/or modified so that their impact on tests of auditory and visual perception is only minimal. To advocate for a stronger theoretical framework than currently exists and to suggest better methodological strategies to improve assessment of auditory processing disorders (APDs). Emphasis is placed on adaptive forced-choice psychophysical methods and the use of matched tasks in multiple sensory modalities to achieve these goals. Together, this approach has potential to improve the construct validity of the diagnosis, enhance and develop theory, and evolve into a preferred method of testing. Examination of methods commonly used in studies of APDs. Where possible, currently used methodology is compared to contemporary psychophysical methods that emphasize computer-controlled forced-choice paradigms. In many cases, the procedures used in studies of APD introduce confounding factors that could be minimized if computer-controlled forced-choice psychophysical methods were utilized. Ambiguities of interpretation, indeterminate diagnoses, and unwanted confounds can be avoided by minimizing memory and attentional demands on the input end and precluding the use of response-selection strategies that use complex motor processes on the output end. Advocated are the use of computer-controlled forced-choice psychophysical paradigms in combination with matched tasks in multiple sensory modalities to enhance the prospect of obtaining a valid diagnosis. American Academy of Audiology.

Using expert opinion to quantify unmeasured confounding bias parameters.

PubMed

Navadeh, Soodabeh; Mirzazadeh, Ali; McFarland, Willi; Woolf-King, Sarah; Mansournia, Mohammad Ali

2016-06-27

To develop and apply a method to quantify bias parameters in the case example of the association between alcohol use and HIV-serodiscordant condomless anal sex with potential confounding by sensation seeking among men who have sex with men (MSM), using expert opinion as an external data source. Through an online survey, we sought the input of 41 epidemiologist and behavioural scientists to quantify six parameters in the population of MSM: the proportion of high sensation seeking among heavy-drinking MSM, the proportion of sensation seeking among low-level drinking MSM, and the risk ratio (RR) of the association between sensation seeking and condomless anal sex, for HIV-positive and HIV-negative MSM. Eleven experts responded. For HIV-positive heavy drinkers, the proportion of high sensation seeking was 53.6% (beta distribution [α=5.50, β=4.78]), and 41.1% (beta distribution [α=3.10, β=4.46]) in HIV-negative heavy drinkers. In HIV-positive low-level alcohol drinkers, high sensation seeking was 26.9% (beta distribution [α=1.81, β=4.92]), similar to high sensation seeking among HIV-negative low-level alcohol drinkers (25.3%) (beta distribution [α=2.00, β=5.89]). The lnRR for the association between sensation seeking and condomless anal sex was ln(2.4) (normal distribution [μ=0.889, σ=0.438]) in HIV-positive and ln(1.5) (normal distribution [μ=0.625, σ=0.391]) in HIV-negative MSM. Expert opinion can be a simple and efficient method for deriving bias parameters to quantify and adjust for hypothesized confounding. In this test case, expert opinion confirmed sensation seeking as a confounder for the effect of alcohol on condomless anal sex and provided the parameters necessary for probabilistic bias analysis.

Sleep quality and methylation status of core circadian rhythm genes among nurses and midwives.

PubMed

Bukowska-Damska, Agnieszka; Reszka, Edyta; Kaluzny, Pawel; Wieczorek, Edyta; Przybek, Monika; Zienolddiny, Shanbeh; Peplonska, Beata

2017-01-01

ABSTARCT Poor sleep quality or sleep restriction is associated with sleepiness and concentration problems. Moreover, chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited recent reports suggest a potential link between sleep deprivation and epigenetic effects such as changes in DNA methylation profiles. The aim of the present study was to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of PER1, PER2, PER3, BMAL1, CLOCK, CRY1 CRY2 and NPAS2 genes, taking into account rotating night work and chronotype as potential confounders or modifiers. A cross-sectional study was conducted on 710 nurses and midwives (347 working on rotating nights and 363 working only during the day) aged 40-60 years. Data from in-person interviews about sleep quality, chronotype and potential confounders were used. Sleep quality and chronotype were assessed using Pittsburgh Sleep Quality Questionnaire (PSQI) and Morningness-Eveningness Questionnaire (MEQ), respectively. Morning blood samples were collected. The methylation status of the circadian rhythm genes was determined via quantitative methylation-specific real-time PCR assays (qMSP) reactions using DNA samples derived from leucocytes. The proportional odds regression model was fitted to quantify the relationship between methylation index (MI) as the dependent variable and sleep quality or sleep duration as the explanatory variable. Analyses were carried out for the total population as well as for subgroups of women stratified by the current system of work (rotating night shift/day work) and chronotype (morning type/intermediate type/evening type). A potential modifying effect of the system of work or the chronotype was examined using the likelihood ratio test. No significant findings were observed in the total study population. Subgroup analyses revealed two statistically significant associations between a shorter sleep duration and 1) methylation level in PER2 among day workers, especially those with the morning chronotype (OR = 2.31, 95%CI:1.24-4.33), and 2) methylation level in CRY2 among subjects with the intermediate chronotype, particularly among day workers (OR = 0.52, 95%CI:0.28-0.96). The study results demonstrated a positive association between average sleep duration of less than 6 hours and the methylation level of PER2 among morning chronotype subjects, and an inverse association for CRY2 among intermediate chronotype subjects, but only among day workers. Both the system of work and the chronotype turned out to be important confounders and modifiers in a number of analyses, making it necessary to consider them as potential covariates in future research on sleep deficiency outcomes. Further studies are warranted to explore this under-investigated topic.

Correction of confounding bias in non-randomized studies by appropriate weighting.

PubMed

Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

2011-03-01

In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Factors associated with employment status before and during pregnancy: Implications for studies of pregnancy outcomes.

PubMed

Rocheleau, Carissa M; Bertke, Stephen J; Lawson, Christina C; Romitti, Paul A; Desrosiers, Tania A; Agopian, Aaron J; Bell, Erin; Gilboa, Suzanne M

2017-04-01

Potential confounding or effect modification by employment status is frequently overlooked in pregnancy outcome studies. To characterize how employed and non-employed women differ, we compared demographics, behaviors, and reproductive histories by maternal employment status for 8,343 mothers of control (non-malformed) infants in the National Birth Defects Prevention Study (1997-2007) and developed a multivariable model for employment status anytime during pregnancy and the 3 months before conception. Sixteen factors were independently associated with employment before or during pregnancy, including: maternal age, pre-pregnancy body mass index, pregnancy intention, periconceptional/first trimester smoking and alcohol consumption, and household income. Employment status was significantly associated with many common risk factors for adverse pregnancy outcomes. Pregnancy outcome studies should consider adjustment or stratification by employment status. In studies of occupational exposures, these differences may cause uncontrollable confounding if non-employed women are treated as unexposed instead of excluded from analysis. Am. J. Ind. Med. 60:329-341, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Motivation as a predictor of speech intelligibility after total laryngectomy.

PubMed

Singer, Susanne; Meyer, Alexandra; Fuchs, Michael; Schock, Juliane; Pabst, Friedemann; Vogel, Hans-Joachim; Oeken, Jens; Sandner, Annett; Koscielny, Sven; Hormes, Karl; Breitenstein, Kerstin; Dietz, Andreas

2013-06-01

It has often been argued that if patients' success with speech rehabilitation after laryngectomy is limited, it is the result of lacking motivation on their part. This project investigated the role of motivation in speech rehabilitation. In a multicenter prospective cohort study, 141 laryngectomees were interviewed at the beginning of rehabilitation and 1 year after laryngectomy. Speech intelligibility was measured with a standardized test, and patients self-assessed their own motivation shortly after the surgery. Logistic regression, adjusted for several theory-based confounding factors, was used to assess the impact of motivation on speech intelligibility. Speech intelligibility 1 year after laryngectomy was not significantly associated with the level of motivation at the beginning of rehabilitation (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.7-2.3; p = .43) after adjusting for the effect of potential confounders (implantation of a voice prosthesis, patient's cognitive abilities, frustration tolerance, physical functioning, and type of rehabilitation). Motivation is not a strong predictor of speech intelligibility 1 year after laryngectomy. Copyright © 2012 Wiley Periodicals, Inc.

Degraded expression of learned feedforward control in movements released by startle.

PubMed

Wright, Zachary A; Carlsen, Anthony N; MacKinnon, Colum D; Patton, James L

2015-08-01

Recent work has shown that preplanned motor programs can be rapidly released via fast conducting pathways using a startling acoustic stimulus. Our question was whether the startle-elicited response might also release a recently learned internal model, which draws on experience to predict and compensate for expected perturbations in a feedforward manner. Our initial investigation using adaptation to robotically produced forces showed some evidence of this, but the results were potentially confounded by co-contraction caused by startle. In this study, we eliminated this confound by asking subjects to make reaching movements in the presence of a visual distortion. Results show that a startle stimulus (1) decreased performance of the recently learned task and (2) reduced after-effect magnitude. Since the recall of learned control was reduced, but not eliminated during startle trials, we suggest that multiple neural centers (cortical and subcortical) are involved in such learning and adaptation. These findings have implications for motor training in areas such as piloting, teleoperation, sports, and rehabilitation.

Real-world effectiveness of 8 weeks treatment with ledipasvir/sofosbuvir in chronic hepatitis C.

PubMed

Buggisch, Peter; Zeuzem, Stefan

2018-05-11

We thank Ojha and Steyerberg for making a good point. Indeed, defining analyses populations of real-life observational studies as ITT or PP is problematic as this wording may suggest a higher comparability to clinical trials as is adequate. In principle, even refined methods for adjusting confounders and minimizing bias cannot fully resolve the inherent problem of confounders in such trials. In our paper the wording (ITT and PP) was chosen for comparability with similar previous observational studies (e.g. Zeng et al) and a lot of effort was made to make the definitions transparent by illustrating them in a Figure and mentioning them several times in the article. Furthermore, the results were carefully discussed and, overall, highly comparable with those from clinical trials. Therefore, potential overestimation of sustained response rates as illustrated and discussed in the letter by Ojha and Steyerberg seems to be a limited problem in our article about this real world data. Copyright © 2018. Published by Elsevier B.V.

Human exposure to high natural background radiation: what can it teach us about radiation risks?

PubMed Central

Hendry, Jolyon H; Simon, Steven L; Wojcik, Andrzej; Sohrabi, Mehdi; Burkart, Werner; Cardis, Elisabeth; Laurier, Dominique; Tirmarche, Margot; Hayata, Isamu

2014-01-01

Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors. PMID:19454802

Smoking, HIV, and risk of pregnancy loss.

PubMed

Westreich, Daniel; Cates, Jordan; Cohen, Mardge; Weber, Kathleen M; Seidman, Dominika; Cropsey, Karen; Wright, Rodney; Milam, Joel; Young, Mary A; Mehta, C Christina; Gustafson, Deborah R; Golub, Elizabeth T; Fischl, Margaret A; Adimora, Adaora A

2017-02-20

Cigarette smoking during pregnancy increases risks of poor pregnancy outcomes including miscarriage and stillbirth (pregnancy loss), but the effect of smoking on pregnancy loss among HIV-infected women has not been explored. Here, investigated the impact of smoking on risk of pregnancy loss among HIV-positive and HIV-negative women, and estimated the potential impact of realistic smoking cessation interventions on risk of pregnancy loss among HIV-positive women. We analyzed pregnancy outcomes in HIV-positive and HIV-negative participants in the Women's Interagency HIV Study between 1994 and 2014. We estimated effects of current smoking at or immediately before pregnancy on pregnancy loss; we controlled for confounding using regression approaches, and estimated potential impact of realistic smoking cessation interventions using a semiparametric g-formula approach. Analysis examined 1033 pregnancies among 659 women. The effect of smoking on pregnancy loss differed dramatically by HIV status: adjusted for confounding, the risk difference comparing current smokers to current nonsmokers was 19.2% (95% confidence limit 10.9-27.5%) in HIV-positive women and 9.7% (95% confidence limit 0.0-19.4%) in HIV-negative women. These results were robust to sensitivity analyses. We estimated that we would need to offer a realistic smoking cessation intervention to 36 women to prevent one pregnancy loss. Smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy. This evidence supports greater efforts to promote smoking cessation interventions among HIV-positive women, especially those who desire to become pregnant.

A Multiyear Assessment of Public Response to a Statewide Drug Take-Back and Disposal Campaign, 2010 to 2012.

PubMed

Yanovitzky, Itzhak

2017-08-01

This study is the first to analyze public response to a drug take-back program, the American Medicine Chest Challenge, in a single state over a period of 3 years (2010-2012). The study utilized a three-wave repeated cross-sectional design and an annual phone survey conducted with a representative sample of adults ( N = 906 in 2010, N = 907 in 2011, and N = 906 in 2012), which assessed exposure to the campaign, drug disposal behaviors, possible mediators of campaign effects (risk appraisal, personal agency, normative influence, and interpersonal talk), and potential confounders. Logistic regression and causal mediation analysis were employed to estimate confounder-adjusted direct and mediated effects of the campaign. Results showed that the campaign reached a sizable portion (50% to 60%) of state adults and that campaign exposure was associated with increased likelihood of having conversations with others about this topic. About 55% of all adults in the state reported taking at least one of the actions recommended by the campaign, and campaign exposure was associated with increased likelihood of disposing of prescription drugs at a drug collection day event (adjusted odds ratio = 4) and of talking to a child about the risks associated with prescription drug abuse (adjusted odds ratio = 2). The causal mediation analysis demonstrated that the campaign influenced audiences by reinforcing their efficacy to safely dispose of prescription drugs, but also potentially by stimulating conversations among community members about this topic. Drug take-back campaigns can be an effective mechanism to decrease the availability of prescription drugs in communities.

Family characteristics and the use of maternal health services: a population-based survey in Eastern China.

PubMed

Zhang, Ling; Xue, Chengbing; Wang, Youjie; Zhang, Liuyi; Liang, Yuan

2016-01-01

Despite the benefits of maternal health services, these services are often underutilized, especially in the developing countries. The aim of the present study is to provide insight regarding factors affecting maternal health services use from the family perspective. We use data from the fourth National Health Services Survey in Jiangsu province of Eastern China to investigate the effect of family characteristics on the use of maternal health services. Family characteristics included whether or not living with parents, age of husband, husband's education, and husband's work status as well as family economic status. Demographic variables, social and environmental factors, and previous reproductive history were taken as potential confounders. Multiple logistic regression models were used to examine the independent effects of the family characteristic variables on maternal health service utilization. The data indicate that the percentages of prenatal care, postnatal visits and hospital delivery were 85.44, 65.12 and 99.59 % respectively. Living with parents was associated with less use of prenatal care and husband's age, education and employment status had no effect on the use of prenatal care after adjusting for potential confounding variables. Our findings suggest that maternal health education (especially the role of prenatal care) needs to be extended beyond the expectant mothers themselves to their parents and husbands. The difference of health care delivery as a result of traditional family culture may highlight the differences in factors influencing the use of postnatal visits and those influencing the use of prenatal care; which may be worthy of further study.

Acute and chronic effect of physical activity on cognition and behaviour in young people with ADHD: A systematic review of intervention studies.

PubMed

Suarez-Manzano, Sara; Ruiz-Ariza, Alberto; De La Torre-Cruz, Manuel; Martínez-López, Emilio J

2018-06-01

Young people with attention deficit hyperactivity disorder (ADHD) often have learning and behavioral control difficulties. The aim of this review is analyse the acute and chronic effect of physical activity (PA) on the cognition and behaviour of children and adolescents with ADHD. Studies were identified in five databases (PubMed, SPORTDiscus, ProQuest, Web of Science, and SCOPUS), from January 2000 through to January 2017. A total of 16 interventional studies met the inclusion criteria. PA practice of 20-30 min (intensity 40-75%) produces a positive acute effect on processing speed, working memory, planning and problem solving in young people with ADHD. However, these effects on behaviour are contradictory and vary depending on age. Chronic PA practice (≥30 min per day, ≥40% intensity, ≥three days per week, ≥five weeks) further improves attention, inhibition, emotional control, behaviour and motor control. The results must be treated with caution, because only 25% of the studies used confounders. More research is needed to justify the causes of these effects. It is necessary to establish programs with regard to the duration, intensity, kind of exercise, and time of PA to improve cognition and behaviour in young people with ADHD taking into account potential confounders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pain and symptoms of depression in older adults living in community and in nursing homes: the role of activity restriction as a potential mediator and moderator.

PubMed

López-Lopez, Almudena; González, José L; Alonso-Fernández, Miriam; Cuidad, Noelia; Matías, Borja

2014-10-01

Chronic pain is likely to lead to depressive symptoms, but the nature of this relationship is not completely clear. The aim of the present study is to analyze the role of activity restriction in the pain-depression relationship in older people, and to test the hypothesis that this role is more relevant in community-dwelling older people than in nursing home residents. Depressive symptoms, pain intensity, and activity restriction were measured in a sample of 208 older adults with osteoarthritis, 102 living in nursing homes (NH), and 106 in the community. Analyses were carried out using moderation and moderated mediation analyses approach, treating activity restriction as a confounder. RESULTS showed a significant confounding effect of activity restriction, interaction effect between pain intensity and activity restriction on depression, and modifying effect of pain intensity on depression by adding activity restriction into the model. These results suggest a potential mediating and moderating effects of activity restriction. Moreover, analyses suggest that, surprisingly, the strength of the mediation could be higher in nursing homes. Overall, it may be that what is really important to emotional well-being is not so much pain itself, but rather the way in which the pain alters older people's lives. The greater strength of the mediation in NH might be understood within the scope of self-determination theory. Generally speaking, the NH context has been considered as a coercive setting, promoting non-autonomous orientation. In this context, when events are objectively coercive, people may lack perceived autonomy and hence be at greater risk of depression.

Why does early sexual intercourse predict subsequent maladjustment? Exploring potential familial confounds.

PubMed

Donahue, Kelly L; Lichtenstein, Paul; Långström, Niklas; D'Onofrio, Brian M

2013-02-01

Previous studies have found an association between early age at first sexual intercourse and subsequent psychosocial maladjustment. Using a quasi-experimental approach, we examined the extent to which this observed association may be due to familial confounds not explored in prior research. Using a population-based cohort of Swedish adult twins (ages 19-47; N = 12,126), we examined the nature of the association between early sexual intercourse (i.e., first intercourse occurring before age 16) and various outcomes reflecting psychosocial health, including substance use, depression, criminal convictions, and adolescent childbearing. We used two methods--discordant-twin analyses and bivariate twin modeling--to estimate the extent to which genetic and environmental confounds explained observed associations. Individuals who engaged in early intercourse were at greater risk for most of the adverse psychosocial health outcomes measured in this study. However, twin pairs discordant for engaging in early intercourse did not differ significantly in their risk for psychosocial maladjustment. Our results indicated that early age at first sexual intercourse and subsequent psychosocial maladjustment may be associated because of familial factors shared by twins. Early intercourse may be associated with poor psychosocial health largely due to shared familial influences rather than through a direct causal connection. Therefore, effective and efficient interventions should address other risk factors common to early intercourse and poor psychosocial health.

High frequency bone conduction auditory evoked potentials in the guinea pig: Assessing cochlear injury after ossicular chain manipulation.

PubMed

Bergin, M J; Bird, P A; Vlajkovic, S M; Thorne, P R

2015-12-01

Permanent high frequency (>4 kHz) sensorineural hearing loss following middle ear surgery occurs in up to 25% of patients. The aetiology of this loss is poorly understood and may involve transmission of supra-physiological forces down the ossicular chain to the cochlea. Investigating the mechanisms of this injury using animal models is challenging, as evaluating cochlear function with evoked potentials is confounded when ossicular manipulation disrupts the normal air conduction (AC) pathway. Bone conduction (BC) using clinical bone vibrators in small animals is limited by poor transducer output at high frequencies sensitive to trauma. The objectives of the present study were firstly to evaluate a novel high frequency bone conduction transducer with evoked auditory potentials in a guinea pig model, and secondly to use this model to investigate the impact of middle ear surgical manipulation on cochlear function. We modified a magnetostrictive device as a high frequency BC transducer and evaluated its performance by comparison with a calibrated AC transducer at frequencies up to 32 kHz using the auditory brainstem response (ABR), compound action potential (CAP) and summating potential (SP). To mimic a middle ear traumatising stimulus, a rotating bur was brought in to contact with the incudomalleal complex and the effect on evoked cochlear potentials was observed. BC-evoked potentials followed the same input-output function pattern as AC potentials for all ABR frequencies. Deterioration in CAP and SP thresholds was observed after ossicular manipulation. It is possible to use high frequency BC to evoke responses from the injury sensitive basal region of the cochlea and so not rely on AC with the potential confounder of conductive hearing loss. Ongoing research explores how these findings evolve over time, and ways in which injury may be reduced and the cochlea protected during middle ear surgery. Copyright © 2015 Elsevier B.V. All rights reserved.

Vasodilators and nootropics as predictors of dementia and mortality in the PAQUID cohort.

PubMed

Dartigues, Jean-François; Carcaillon, Laure; Helmer, Catherine; Lechevallier, Nathalie; Lafuma, Antoine; Khoshnood, Babak

2007-03-01

To assess the effects of treatment for memory impairment and the Ginkgo biloba extract (EGb 761) on dementia, mortality, and survival without dementia. Prospective community-based cohort study. France. Three thousand five hundred thirty-four subjects aged 65 and older. Information on drug consumption was obtained by interview and visual assessment of patients' medicine chests. Active screening of dementia was performed every 2 years over a 13-year period. The independent effects of treatment for memory impairment and the Ginkgo biloba extract on the risks of dementia and death were estimated using Cox proportional hazards models, adjusted for potentially confounding factors (including comorbidities). The initial consumption of Ginkgo biloba did not modify the risk of dementia (relative risk (RR)=1.16, 95% confidence interval (CI)=0.84-1.60), whereas the consumption of other treatments for memory impairment was associated with a higher risk of dementia (RR=1.35, 95% CI=1.11-1.63). Subjects who took Ginkgo biloba had a significantly lower risk of mortality in the long term (RR=0.76, 95% CI=0.62-0.93), even after adjustment for potentially confounding factors. The initial consumption of treatment for memory impairment other than Ginkgo biloba did not modify the risk of mortality. These results suggest that treatment with EGb 761 may increase the probability of survival in the elderly population. These findings need to be corroborated and further assessed using randomized, controlled trials.

Protection reduces loss of natural land-cover at sites of conservation importance across Africa.

PubMed

Beresford, Alison E; Eshiamwata, George W; Donald, Paul F; Balmford, Andrew; Bertzky, Bastian; Brink, Andreas B; Fishpool, Lincoln D C; Mayaux, Philippe; Phalan, Ben; Simonetti, Dario; Buchanan, Graeme M

2013-01-01

There is an emerging consensus that protected areas are key in reducing adverse land-cover change, but their efficacy remains difficult to quantify. Many previous assessments of protected area effectiveness have compared changes between sets of protected and unprotected sites that differ systematically in other potentially confounding respects (e.g. altitude, accessibility), have considered only forest loss or changes at single sites, or have analysed changes derived from land-cover data of low spatial resolution. We assessed the effectiveness of protection in reducing land-cover change in Important Bird Areas (IBAs) across Africa using a dedicated visual interpretation of higher resolution satellite imagery. We compared rates of change in natural land-cover over a c. 20-year period from around 1990 at a large number of points across 45 protected IBAs to those from 48 unprotected IBAs. A matching algorithm was used to select sample points to control for potentially confounding differences between protected and unprotected IBAs. The rate of loss of natural land-cover at sample points within protected IBAs was just 42% of that at matched points in unprotected IBAs. Conversion was especially marked in forests, but protection reduced rates of forest loss by a similar relative amount. Rates of conversion increased from the centre to the edges of both protected and unprotected IBAs, but rates of loss in 20-km buffer zones surrounding protected IBAs and unprotected IBAs were similar, with no evidence of displacement of conversion from within protected areas to their immediate surrounds (leakage).

Effect of tobacco smoke on the oral health of U.S. women of childbearing age.

PubMed

Iida, Hiroko; Kumar, Jayanth V; Kopycka-Kedzierawski, Dorota T; Billings, Ronald J

2009-01-01

To determine the oral health status of US women of childbearing age and to analyze the effect of tobacco smoke on their oral health. Data from the 1999-2004 National Health and Nutrition Examination Survey were evaluated for women 15-44 years of age. The association of exposure to tobacco smoke with untreated caries, mean DMFS, gingivitis, and periodontitis were examined in bivariate and regression analyses controlling for potential confounders. The prevalence of untreated caries was 25%, for gingivitis 49%, and for periodontitis 6%. After adjusting for potential confounders, self-reported current smoking was a strong independent risk indicator for untreated caries, periodontitis, and to a lesser extent for greater DMFS count. Women with detectable cotinine levels below 15 ng/mL presented with an increased risk for gingivitis. Independent factors associated with increased risk for untreated caries were being Black, having less than a high school education, Medicaid or no health insurance, previous live births, and infrequent and episodic dental visits. Characteristics associated with gingivitis were being Mexican-American, obese, pregnant, and having infrequent dental visits. Older age, no insurance, and the last dental visit for treatment were independently associated with periodontitis. Dental caries and periodontitis were prevalent among certain subgroups of women of reproductive age. Smoking was found to be a significant risk indicator for various negative oral health outcomes. Barriers to accessing to dental care that were manifested by untreated caries among Black women, mothers, and Medicaid beneficiaries must be better understood.

The interpersonally sensitive disposition and health: an integrative review.

PubMed

Marin, Teresa J; Miller, Gregory E

2013-09-01

This article reviews studies that have examined the association between constructs related to interpersonal sensitivity (IS) and morbidity and mortality from major medical illnesses. We define IS as a stable trait characterized by ongoing concerns about negative social evaluation. This disposition makes people vigilant for as well as sensitive to others' evaluations of them. To avoid negative social evaluation, they adopt defensive behaviors such as submission and inhibition. Aspects of IS are captured by various constructs, including introversion, rejection sensitivity, social inhibition, social anxiety, and submissiveness. The review includes 76 long-term prospective studies across 4 outcome categories, namely, infectious disease, cancer, cardiovascular disease (CVD), and all-cause mortality. Three general conclusions are established. First, IS individuals are at increased risk of infectious diseases and possibly CVD, but not cancer and not all-cause mortality. Second, the positive studies provide evidence that IS temporally precedes disease, and go a long way toward ruling out the most plausible alternative explanations based on confounders, supporting a tentative causal interpretation of the data. However, unmeasured potential confounders make it impossible to be certain about whether IS drives the effects on mortality and morbidity. Third, the effects of introversion are accentuated and may only become apparent in contexts that activate social-evaluative concerns (e.g., exposure to early life residential mobility, living with the stigma of human immunodeficiency virus). Findings are discussed in regard to potential psychosocial and psychobiological mechanisms as well as implications for future work concerning IS and health. (c) 2013 APA, all rights reserved.

Analyzing partially missing confounder information in comparative effectiveness and safety research of therapeutics.

PubMed

Toh, Sengwee; García Rodríguez, Luis A; Hernán, Miguel A

2012-05-01

Electronic healthcare databases are commonly used in comparative effectiveness and safety research of therapeutics. Many databases now include additional confounder information in a subset of the study population through data linkage or data collection. We described and compared existing methods for analyzing such datasets. Using data from The Health Improvement Network and the relation between non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding as an example, we employed several methods to handle partially missing confounder information. The crude odds ratio (OR) of upper gastrointestinal bleeding was 1.50 (95% confidence interval: 0.98, 2.28) among selective cyclo-oxygenase-2 inhibitor initiators (n = 43 569) compared with traditional non-steroidal anti-inflammatory drug initiators (n = 411 616). The OR dropped to 0.81 (0.52, 1.27) upon adjustment for confounders recorded for all patients. When further considering three additional variables missing in 22% of the study population (smoking, alcohol consumption, body mass index), the OR was between 0.80 and 0.83 for the missing-category approach, the missing-indicator approach, single imputation by the most common category, multiple imputation by chained equations, and propensity score calibration. The OR was 0.65 (0.39, 1.09) and 0.67 (0.38, 1.16) for the unweighted and the inverse probability weighted complete-case analysis, respectively. Existing methods for handling partially missing confounder data require different assumptions and may produce different results. The unweighted complete-case analysis, the missing-category/indicator approach, and single imputation require often unrealistic assumptions and should be avoided. In this study, differences across methods were not substantial, likely due to relatively low proportion of missingness and weak confounding effect by the three additional variables upon adjustment for other variables. Copyright © 2012 John Wiley & Sons, Ltd.

A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data.

PubMed

Agogo, George O; van der Voet, Hilko; van 't Veer, Pieter; Ferrari, Pietro; Muller, David C; Sánchez-Cantalejo, Emilio; Bamia, Christina; Braaten, Tonje; Knüppel, Sven; Johansson, Ingegerd; van Eeuwijk, Fred A; Boshuizen, Hendriek C

2016-10-13

Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data. We proposed a method to adjust for the bias in the diet-disease association (hereafter, association), due to measurement error in dietary intake and a mismeasured confounder, when there is no internal validation data. The method combines prior information on the validity of the self-report instrument with the observed data to adjust for the bias in the association. We compared the proposed method with the method that ignores the confounder effect, and with the method that ignores measurement errors completely. We assessed the sensitivity of the estimates to various magnitudes of measurement error, error correlations and uncertainty in the literature-reported validation data. We applied the methods to fruits and vegetables (FV) intakes, cigarette smoking (confounder) and all-cause mortality data from the European Prospective Investigation into Cancer and Nutrition study. Using the proposed method resulted in about four times increase in the strength of association between FV intake and mortality. For weakly correlated errors, measurement error in the confounder minimally affected the hazard ratio estimate for FV intake. The effect was more pronounced for strong error correlations. The proposed method permits sensitivity analysis on measurement error structures and accounts for uncertainties in the reported validity coefficients. The method is useful in assessing the direction and quantifying the magnitude of bias in the association due to measurement errors in the confounders.

Youth appraisals of inter-parental conflict and genetic and environmental contributions to attention-deficit hyperactivity disorder: examination of GxE effects in a twin sample.

PubMed

Nikolas, Molly; Klump, Kelly L; Burt, S Alexandra

2012-05-01

Identification of gene x environment interactions (GxE) for attention-deficit hyperactivity disorder (ADHD) is a crucial component to understanding the mechanisms underpinning the disorder, as prior work indicates large genetic influences and numerous environmental risk factors. Building on prior research, children's appraisals of self-blame were examined as a psychosocial moderator of latent etiological influences on ADHD via biometric twin models, which provide an omnibus test of GxE while managing the potential confound of gene-environment correlation. Participants were 246 twin pairs (total n = 492) ages 6-16 years. ADHD behaviors were assessed via mother report on the Child Behavior Checklist. To assess level of self-blame, each twin completed the Children's Perception of Inter-parental Conflict scale. Two biometric GxE models were fit to the data. The first model revealed a significant decrease in genetic effects and a significant increase in unique environmental influences on ADHD with increasing levels of self-blame. These results generally persisted even after controlling for confounding effects due to gene-environment correlation in the second model. Results suggest that appraisals of self-blame in relation to inter-parental conflict may act as a key moderator of etiological contributions to ADHD.

Youth Appraisals of Inter-parental Conflict and Genetic and Environmental Contributions to Attention-Deficit Hyperactivity Disorder: Examination of G×E Effects in a Twin Sample

PubMed Central

Klump, Kelly L.; Burt, S. Alexandra

2012-01-01

Identification of gene × environment interactions (GxE) for attention-deficit hyperactivity disorder (ADHD) is a crucial component to understanding the mechanisms underpinning the disorder, as prior work indicates large genetic influences and numerous environmental risk factors. Building on prior research, children's appraisals of self-blame were examined as a psychosocial moderator of latent etiological influences on ADHD via biometric twin models, which provide an omnibus test of GxE while managing the potential confound of gene-environment correlation. Participants were 246 twin pairs (total n=492) ages 6–16 years. ADHD behaviors were assessed via mother report on the Child Behavior Checklist. To assess level of self-blame, each twin completed the Children's Perception of Inter-parental Conflict scale. Two biometric GxE models were fit to the data. The first model revealed a significant decrease in genetic effects and a significant increase in unique environmental influences on ADHD with increasing levels of self-blame. These results generally persisted even after controlling for confounding effects due to gene-environment correlation in the second model. Results suggest that appraisals of self-blame in relation to inter-parental conflict may act as a key moderator of etiological contributions to ADHD. PMID:22006350

Racial and ethnic differences in utilization of mental health services among high-risk youths.

PubMed

Garland, Ann F; Lau, Anna S; Yeh, May; McCabe, Kristen M; Hough, Richard L; Landsverk, John A

2005-07-01

Racial and ethnic disparities in mental health service use have been identified as a major public health problem. However, the extent to which these disparities may be accounted for by other confounding sociodemographic or clinical predictors of service use (e.g., family income, functional impairment, caregiver strain) is relatively unexplored, especially for youth services. The goal of this study was to test for racial/ethnic disparities in use of a variety of outpatient, inpatient, and informal mental health services among high-risk youths, with the effects of other predictive factors controlled. Participants were 1,256 youths ages 6-18 years who received services in a large, publicly funded system of care (including the child welfare, juvenile justice, special education, alcohol and drug abuse, and mental health service sectors). Youths and caregivers were interviewed with established measures of mental health service use, psychiatric diagnoses, functional impairment, caregiver strain, and parental depression. Significant racial/ethnic group differences in likelihood of receiving any mental health service and, specifically, formal outpatient services were found after the effects of potentially confounding variables were controlled. Race/ethnicity did not exert a significant effect on the use of informal or 24-hour-care services. Racial/ethnic disparities in service use remain a public health problem.

Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?

PubMed

Fish, Alexandra E; Capra, John A; Bush, William S

2016-10-06

The importance of epistasis-or statistical interactions between genetic variants-to the development of complex disease in humans has been controversial. Genome-wide association studies of statistical interactions influencing human traits have recently become computationally feasible and have identified many putative interactions. However, statistical models used to detect interactions can be confounded, which makes it difficult to be certain that observed statistical interactions are evidence for true molecular epistasis. In this study, we investigate whether there is evidence for epistatic interactions between genetic variants within the cis-regulatory region that influence gene expression after accounting for technical, statistical, and biological confounding factors. We identified 1,119 (FDR = 5%) interactions that appear to regulate gene expression in human lymphoblastoid cell lines, a tightly controlled, largely genetically determined phenotype. Many of these interactions replicated in an independent dataset (90 of 803 tested, Bonferroni threshold). We then performed an exhaustive analysis of both known and novel confounders, including ceiling/floor effects, missing genotype combinations, haplotype effects, single variants tagged through linkage disequilibrium, and population stratification. Every interaction could be explained by at least one of these confounders, and replication in independent datasets did not protect against some confounders. Assuming that the confounding factors provide a more parsimonious explanation for each interaction, we find it unlikely that cis-regulatory interactions contribute strongly to human gene expression, which calls into question the relevance of cis-regulatory interactions for other human phenotypes. We additionally propose several best practices for epistasis testing to protect future studies from confounding. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Erectile dysfunction and fruit/vegetable consumption among diabetic Canadian men.

PubMed

Wang, Feng; Dai, Sulan; Wang, Mingdong; Morrison, Howard

2013-12-01

To evaluate the association between fruit/vegetable consumption and erectile dysfunction (ED) among Canadian men with diabetes. Data from the 2011 Survey on Living with Chronic Diseases in Canada - Diabetes Component were analyzed using Statistical Analysis System Enterprise Guide (SAS EG). Respondents were asked a series questions related to their sociodemographics, lifestyle, and chronic health conditions. The association between fruit/vegetable consumption and ED was examined using logistic regression after controlling for potential confounding factors. Bootstrap procedure was used to estimate sample distribution and calculate confidence intervals. Overall, 26.2% of respondents reported having ED. The prevalence increased with age and duration of diabetes. Compared with respondents without ED, those with ED were more likely to be obese, smokers, physically inactive, and either divorced, widowed, or separated. Diabetes complications such as nerve damage, circulation problems, and kidney failure or kidney disease were also significantly associated with ED. After controlling for potential confounding factors, a 10% risk reduction of ED was found with each additional daily serving of fruit/vegetable consumed. ED is common among Canadian men with diabetes. ED was highly associated with age, duration of diabetes, obesity, smoking, and the presence of other diabetes-related complications. Fruit and vegetable consumption might have a protective effect against ED. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Association between periodontal flap surgery for periodontitis and vasculogenic erectile dysfunction in Koreans.

PubMed

Lee, Jae-Hong; Choi, Jung-Kyu; Kim, Sang-Hyun; Cho, Kyung-Hyun; Kim, Young-Taek; Choi, Seong-Ho; Jung, Ui-Won

2017-04-01

The National Health Insurance Service-National Sample Cohort and medical checkup data from 2002 to 2013 were used to evaluate the association between periodontal surgery for the treatment of periodontitis (PSTP) and vasculogenic erectile dysfunction (VED). Bivariate and multivariate logistic regression analyses were applied to a longitudinal retrospective database to assess the association between PSTP and VED while adjusting for the potential confounding effects of sociodemographic factors (age, household income, insurance status, health status, residence area, and smoking status) and comorbidities (diabetes mellitus, angina pectoris, cerebral infarction, and myocardial infarction). Among the 7,148 PSTP within the 268,296 recruited subjects, the overall prevalence of VED in PSTP was 1.43% (n=102). The bivariate analysis showed that VED was significantly related to PSTP (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.38-2.06; P <0.001), and this was confirmed in the multivariate analysis after adjusting for sociodemographic factors and comorbidities (OR, 1.29; 95% CI, 1.06-1.58; P =0.002). Subjects with a history of periodontal flap surgery had a significantly higher risk of VED, after adjusting for potential confounding factors. Further studies are required to identify the key mechanisms underlying the association between severe periodontal disease and VED.

Association between periodontal flap surgery for periodontitis and vasculogenic erectile dysfunction in Koreans

PubMed Central

2017-01-01

Purpose The National Health Insurance Service-National Sample Cohort and medical checkup data from 2002 to 2013 were used to evaluate the association between periodontal surgery for the treatment of periodontitis (PSTP) and vasculogenic erectile dysfunction (VED). Methods Bivariate and multivariate logistic regression analyses were applied to a longitudinal retrospective database to assess the association between PSTP and VED while adjusting for the potential confounding effects of sociodemographic factors (age, household income, insurance status, health status, residence area, and smoking status) and comorbidities (diabetes mellitus, angina pectoris, cerebral infarction, and myocardial infarction). Results Among the 7,148 PSTP within the 268,296 recruited subjects, the overall prevalence of VED in PSTP was 1.43% (n=102). The bivariate analysis showed that VED was significantly related to PSTP (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.38–2.06; P<0.001), and this was confirmed in the multivariate analysis after adjusting for sociodemographic factors and comorbidities (OR, 1.29; 95% CI, 1.06–1.58; P=0.002). Conclusions Subjects with a history of periodontal flap surgery had a significantly higher risk of VED, after adjusting for potential confounding factors. Further studies are required to identify the key mechanisms underlying the association between severe periodontal disease and VED. PMID:28462008

Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

PubMed

Godos, Justyna; Micek, Agnieszka; Marranzano, Marina; Salomone, Federico; Rio, Daniele Del; Ray, Sumantra

2017-08-28

A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose–Response Meta-Analysis of Prospective Cohort Studies

PubMed Central

Micek, Agnieszka; Marranzano, Marina; Ray, Sumantra

2017-01-01

Background: A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Methods: Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose–response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. Results: We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose–response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). Conclusions: The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC. PMID:28846640

Dietary Patterns and Insomnia Symptoms in Chinese Adults: The China Kadoorie Biobank.

PubMed

Yu, Canqing; Shi, Zumin; Lv, Jun; Guo, Yu; Bian, Zheng; Du, Huaidong; Chen, Yiping; Tao, Ran; Huang, Ying; Chen, Junshi; Chen, Zhengming; Li, Liming

2017-03-04

Limited attention has been paid to the effect of dietary patterns on sleep problems. In the present study, we analyzed the cross-sectional data of 481,242 adults aged 30-79 years from the China Kadoorie Biobank. A laptop-based questionnaire was administered to collect information on food intakes and insomnia symptoms. Logistic regression was used to estimate the odds ratios of each insomnia symptom according to quartiles of each dietary pattern, with adjustment for potential confounders. Two major dietary patterns were derived by factor analysis. The traditional northern dietary pattern was characterized by high intakes of wheat and other staple food, whereas the modern dietary pattern was characterized by high intakes of meat, poultry, fish, eggs, fresh fruit, and dairy products. Both dietary patterns were associated with a decreased prevalence of insomnia symptoms ( p for trend < 0.001); after adjustment for potential confounders, individuals who had the highest quartile score of traditional northern dietary pattern were 12%-19% less likely to have insomnia symptoms compared to those in the lowest quartile (odds ratio: 0.81-0.88), and the corresponding values for the modern dietary pattern were 0.89-1.01. Furthermore, interactions of these two dietary patterns on insomnia symptoms were observed. Further prospective studies are needed to elucidate the relationship between diet and insomnia.

Social class, income, education, area of residence and psychological distress: does social class have an independent effect on psychological distress in Antalya, Turkey?

PubMed

Belek, I

2000-02-01

The aim of this study is to determine the separate effects of social class, income, education and area of residence on psychological distress. The study also assesses whether the association between prevalence of high score on the 12-item General Health Questionnaire (GHQ 12) and social class is independent of other variables. Psychological distress was assessed by means of the GHQ 12. The study covered 1,092 adults aged 15 years or more living in two different quarters of Antalya. Social class status was defined by occupational position, with income, education and area of residence treated as confounders. Chi-square and logistic regression analyses were used to evaluate the data. Large inequalities in psychological distress by all variables were observed. Psychological distress was significantly associated with class status, after adjusting for income, education, area of residence and other potential confounders (age, sex and marital status). Class inequalities in psychological distress were observed between blue-collar workers/unqualified employees and bourgeoisie. These findings support the view that the recent widening of inequalities among social classes in Turkey pose a substantial threat to health.

Identifying barriers to Muslim integration in France

PubMed Central

Adida, Claire L.; Laitin, David D.; Valfort, Marie-Anne

2010-01-01

Is there a Muslim disadvantage in economic integration for second-generation immigrants to Europe? Previous research has failed to isolate the effect that religion may have on an immigrant family's labor market opportunities because other factors, such as country of origin or race, confound the result. This paper uses a correspondence test in the French labor market to identify and measure this religious effect. The results confirm that in the French labor market, anti-Muslim discrimination exists: a Muslim candidate is 2.5 times less likely to receive a job interview callback than is his or her Christian counterpart. A high-n survey reveals, consistent with expectations from the correspondence test, that second-generation Muslim households in France have lower income compared with matched Christian households. The paper thereby contributes to both substantive debates on the Muslim experience in Europe and methodological debates on how to measure discrimination. Following the National Academy of Sciences’ 2001 recommendations on combining a variety of methodologies and applying them to real-world situations, this research identifies, measures, and infers consequences of discrimination based on religious affiliation, controlling for potentially confounding factors, such as race and country of origin. PMID:21098283

Associations between proximity to livestock farms, primary health care visits and self-reported symptoms.

PubMed

van Dijk, Christel E; Smit, Lidwien A M; Hooiveld, Mariette; Zock, Jan-Paul; Wouters, Inge M; Heederik, Dick J J; Yzermans, C Joris

2016-02-19

Living in a neighbourhood with a high density of livestock farms has been associated with adverse respiratory health effects, but less is known about healthcare utilisation. This study aimed at investigating the associations between livestock exposure and primary health care visits and self-reported symptoms. In addition, we examined the potentially confounding effect of distance from home to general practice. Contact data between 2006 and 2009 were obtained from electronic medical records of 54,777 persons registered within 16 general practices in an area with a high density of livestock farms in the Netherlands. Data on self-reported symptoms were used from a cross-sectional sample of 531 patients in 2010. Livestock presence in a 500 m radius from home was computed using Geographic Information System data. In general, livestock exposure was associated with fewer contacts and self-reported symptoms for respiratory and other conditions. The number of poultry within 500 m was positively associated with the number of contacts. A longer distance to general practice was associated with fewer contacts, but did not confound associations. People living close to livestock farms less often see their general practitioner and report symptoms.

A Tutorial in Bayesian Potential Outcomes Mediation Analysis.

PubMed

Miočević, Milica; Gonzalez, Oscar; Valente, Matthew J; MacKinnon, David P

2018-01-01

Statistical mediation analysis is used to investigate intermediate variables in the relation between independent and dependent variables. Causal interpretation of mediation analyses is challenging because randomization of subjects to levels of the independent variable does not rule out the possibility of unmeasured confounders of the mediator to outcome relation. Furthermore, commonly used frequentist methods for mediation analysis compute the probability of the data given the null hypothesis, which is not the probability of a hypothesis given the data as in Bayesian analysis. Under certain assumptions, applying the potential outcomes framework to mediation analysis allows for the computation of causal effects, and statistical mediation in the Bayesian framework gives indirect effects probabilistic interpretations. This tutorial combines causal inference and Bayesian methods for mediation analysis so the indirect and direct effects have both causal and probabilistic interpretations. Steps in Bayesian causal mediation analysis are shown in the application to an empirical example.

Case-control studies of the efficacy of cancer screening: overcoming bias from nonrandom patterns of screening.

PubMed

Weiss, Noel S; Dhillon, Preet K; Etzioni, Ruth

2004-07-01

A case-control study of the efficacy of cancer screening, like any other case-control study, must deal with potential confounding. There are 2 categories of confounding variables that pose special problems for studies of screening: (1) age and calendar time resulting from different temporal distributions of screening between cases and controls irrespective of whether the screening test leads to a reduction in mortality; and (2) the administration of other screening tests for the cancer in question when it is not clear whether the result of the other test had a bearing on the decision to order the test under study. We describe circumstances in which confounding from these sources can be dealt with satisfactorily by means of restriction or adjustment, and other circumstances in which it cannot. Copyright 2004 Lippincott Williams and Wilkins

Revisiting the Table 2 fallacy: A motivating example examining preeclampsia and preterm birth.

PubMed

Bandoli, Gretchen; Palmsten, Kristin; Chambers, Christina D; Jelliffe-Pawlowski, Laura L; Baer, Rebecca J; Thompson, Caroline A

2018-05-21

A "Table Fallacy," as coined by Westreich and Greenland, reports multiple adjusted effect estimates from a single model. This practice, which remains common in published literature, can be problematic when different types of effect estimates are presented together in a single table. The purpose of this paper is to quantitatively illustrate this potential for misinterpretation with an example estimating the effects of preeclampsia on preterm birth. We analysed a retrospective population-based cohort of 2 963 888 singleton births in California between 2007 and 2012. We performed a modified Poisson regression to calculate the total effect of preeclampsia on the risk of PTB, adjusting for previous preterm birth. pregnancy alcohol abuse, maternal education, and maternal socio-demographic factors (Model 1). In subsequent models, we report the total effects of previous preterm birth, alcohol abuse, and education on the risk of PTB, comparing and contrasting the controlled direct effects, total effects, and confounded effect estimates, resulting from Model 1. The effect estimate for previous preterm birth (a controlled direct effect in Model 1) increased 10% when estimated as a total effect. The risk ratio for alcohol abuse, biased due to an uncontrolled confounder in Model 1, was reduced by 23% when adjusted for drug abuse. The risk ratio for maternal education, solely a predictor of the outcome, was essentially unchanged. Reporting multiple effect estimates from a single model may lead to misinterpretation and lack of reproducibility. This example highlights the need for careful consideration of the types of effects estimated in statistical models. © 2018 John Wiley & Sons Ltd.

Mismeasurement and the resonance of strong confounders: uncorrelated errors.

PubMed

Marshall, J R; Hastrup, J L

1996-05-15

Greenland first documented (Am J Epidemiol 1980; 112:564-9) that error in the measurement of a confounder could resonate--that it could bias estimates of other study variables, and that the bias could persist even with statistical adjustment for the confounder as measured. An important question is raised by this finding: can such bias be more than trivial within the bounds of realistic data configurations? The authors examine several situations involving dichotomous and continuous data in which a confounder and a null variable are measured with error, and they assess the extent of resultant bias in estimates of the effect of the null variable. They show that, with continuous variables, measurement error amounting to 40% of observed variance in the confounder could cause the observed impact of the null study variable to appear to alter risk by as much as 30%. Similarly, they show, with dichotomous independent variables, that 15% measurement error in the form of misclassification could lead the null study variable to appear to alter risk by as much as 50%. Such bias would result only from strong confounding. Measurement error would obscure the evidence that strong confounding is a likely problem. These results support the need for every epidemiologic inquiry to include evaluations of measurement error in each variable considered.

Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 2, Diagnostic Performance, Confounders, and Future Directions

PubMed Central

Tang, An; Cloutier, Guy; Szeverenyi, Nikolaus M.; Sirlin, Claude B.

2016-01-01

OBJECTIVE The purpose of the article is to review the diagnostic performance of ultrasound and MR elastography techniques for detection and staging of liver fibrosis, the main current clinical applications of elastography in the abdomen. CONCLUSION Technical and instrument-related factors and biologic and patient-related factors may constitute potential confounders of stiffness measurements for assessment of liver fibrosis. Future developments may expand the scope of elastography for monitoring liver fibrosis and predict complications of chronic liver disease. PMID:25905762

Laughter and humour interventions for well-being in older adults: A systematic review and intervention classification.

PubMed

Gonot-Schoupinsky, F N; Garip, G

2018-06-01

To assess the potential of laughter and humour interventions to increase well-being in a general population of adults aged 60 plus; and to develop a classification to compare approaches and potential benefits of different intervention types. A systematic search of Web of Science, PubMed/MEDLINE, PsychInfo, AMED, and PsychArticles used inclusive terms relating to laughter and humour interventions. A realist synthesis approach enabled heterogeneous interventions to be compared pragmatically. Five laughter interventions, and one humour intervention, using one or more outcome related to well-being, were considered for inclusion after screening 178 primary research papers. The five laughter interventions, representing a sample of 369 participants, were retained. Well-being related outcome measures reported in each intervention informed efficacy; Joanna Briggs Institute tools appraised design; and a realist approach enabled heterogeneous interventions to be measured on their overall potential to provide an evidence base. Well-being related measures demonstrated at least one significant positive effect in all interventions. Confounding factors inherent in the intervention types were observed. Individual participant laughter was not reported. Laughter and humour interventions appear to enhance well-being. There is insufficient evidence for the potential of laughter itself to increase well-being as interventions contained a range of confounding factors and did not measure participant laughter. Interventions that isolate, track, and measure the parameters of individual laughter are recommended to build evidence for these potentially attractive and low-risk interventions. The classification proposed may guide the development of both evidence-oriented and population-appropriate intervention designs. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Time-varying effect moderation using the structural nested mean model: estimation using inverse-weighted regression with residuals

PubMed Central

Almirall, Daniel; Griffin, Beth Ann; McCaffrey, Daniel F.; Ramchand, Rajeev; Yuen, Robert A.; Murphy, Susan A.

2014-01-01

This article considers the problem of examining time-varying causal effect moderation using observational, longitudinal data in which treatment, candidate moderators, and possible confounders are time varying. The structural nested mean model (SNMM) is used to specify the moderated time-varying causal effects of interest in a conditional mean model for a continuous response given time-varying treatments and moderators. We present an easy-to-use estimator of the SNMM that combines an existing regression-with-residuals (RR) approach with an inverse-probability-of-treatment weighting (IPTW) strategy. The RR approach has been shown to identify the moderated time-varying causal effects if the time-varying moderators are also the sole time-varying confounders. The proposed IPTW+RR approach provides estimators of the moderated time-varying causal effects in the SNMM in the presence of an additional, auxiliary set of known and measured time-varying confounders. We use a small simulation experiment to compare IPTW+RR versus the traditional regression approach and to compare small and large sample properties of asymptotic versus bootstrap estimators of the standard errors for the IPTW+RR approach. This article clarifies the distinction between time-varying moderators and time-varying confounders. We illustrate the methodology in a case study to assess if time-varying substance use moderates treatment effects on future substance use. PMID:23873437

On the use and misuse of scalar scores of confounders in design and analysis of observational studies.

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

We assess the asymptotic bias of estimates of exposure effects conditional on covariates when summary scores of confounders, instead of the confounders themselves, are used to analyze observational data. First, we study regression models for cohort data that are adjusted for summary scores. Second, we derive the asymptotic bias for case-control studies when cases and controls are matched on a summary score, and then analyzed either using conditional logistic regression or by unconditional logistic regression adjusted for the summary score. Two scores, the propensity score (PS) and the disease risk score (DRS) are studied in detail. For cohort analysis, when regression models are adjusted for the PS, the estimated conditional treatment effect is unbiased only for linear models, or at the null for non-linear models. Adjustment of cohort data for DRS yields unbiased estimates only for linear regression; all other estimates of exposure effects are biased. Matching cases and controls on DRS and analyzing them using conditional logistic regression yields unbiased estimates of exposure effect, whereas adjusting for the DRS in unconditional logistic regression yields biased estimates, even under the null hypothesis of no association. Matching cases and controls on the PS yield unbiased estimates only under the null for both conditional and unconditional logistic regression, adjusted for the PS. We study the bias for various confounding scenarios and compare our asymptotic results with those from simulations with limited sample sizes. To create realistic correlations among multiple confounders, we also based simulations on a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

Conceptualizing and measuring personality vulnerability to depression: comment on Coyne and Whiffen (1995).

PubMed

Zuroff, David C; Mongrain, Myriam; Santor, Darcy A

2004-05-01

J. C. Coyne and V. E. Whiffen (1995) reviewed research on personality vulnerability to depression, focusing on S. J. Blatt's (1974, 1990) concepts of dependency and self-criticism and A. T. Beck's (1983) concepts of sociotropy and autonomy. The authors discuss 6 issues raised in that review: (a) the typological or dimensional nature of vulnerability, (b) the theoretical implications of "mixed" vulnerability, (c) the relations of vulnerability to Neuroticism. (d) the potential confounding of vulnerability with concurrent depression, (e) the potential confounding of vulnerability with social context, and (f) the differentiation of dependency from relatedness. The authors conclude that Blatt's and Beck's concepts are continuous, nearly orthogonal dimensions that can be identified and measured independently from Neuroticism, depression, and social context. ((c) 2004 APA, all rights reserved)

Event-related brain potentials to violations of arithmetic syntax represented by place value structure.

PubMed

Szucs, Dénes; Soltész, Fruzsina

2010-05-01

We dissociated ERP markers of semantic (numerical distance) vs. syntactic (place value) incongruence in the domain of arithmetic. Participants verified additions with four-digit numbers. Semantic incongruencies elicited the N400 ERP effect. A centro-parietal (putative P600) effect to place value violations was not related to arithmetic syntax. Rather, this effect was an enlarged P3b reflecting different surprise values of place value vs. non-place value violations. This potential confound should be considered in numerical cognition experiments. The latency of the N400 and P3a effects were differentially affected by place value analysis. The amplitude of the P3a and that of a fronto-central positive effect (FP600) was sensitive to place value analysis and digit content. Results suggest that ERPs can index the syntactical analysis of multi-digit numbers. Both ERP and behavioral data confirmed that multi-digit numbers were decomposed into their constituent digits, rather than evaluated holistically. Copyright 2010 Elsevier B.V. All rights reserved.

Influence of potentially confounding factors on sea urchin porewater toxicity tests

USGS Publications Warehouse

Carr, R.S.; Biedenbach, J.M.; Nipper, M.

2006-01-01

The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.

Reproductive history and post-reproductive mortality: A sibling comparison analysis using Swedish register data.

PubMed

Barclay, Kieron; Keenan, Katherine; Grundy, Emily; Kolk, Martin; Myrskylä, Mikko

2016-04-01

A growing body of evidence suggests that reproductive history influences post-reproductive mortality. A potential explanation for this association is confounding by socioeconomic status in the family of origin, as socioeconomic status is related to both fertility behaviours and to long-term health. We examine the relationship between age at first birth, completed parity, and post-reproductive mortality and address the potential confounding role of family of origin. We use Swedish population register data for men and women born 1932-1960, and examine both all-cause and cause-specific mortality. The contributions of our study are the use of a sibling comparison design that minimizes residual confounding from shared family background characteristics and assessment of cause-specific mortality that can shed light on the mechanisms linking reproductive history to mortality. Our results were entirely consistent with previous research on this topic, with teenage first time parents having higher mortality, and the relationship between parity and mortality following a U-shaped pattern where childless men and women and those with five or more children had the highest mortality. These results indicate that selection into specific fertility behaviours based upon socioeconomic status and experiences within the family of origin does not explain the relationship between reproductive history and post-reproductive mortality. Additional analyses where we adjust for other lifecourse factors such as educational attainment, attained socioeconomic status, and post-reproductive marital history do not change the results. Our results add an important new level of robustness to the findings on reproductive history and mortality by showing that the association is robust to confounding by factors shared by siblings. However it is still uncertain whether reproductive history causally influences health, or whether other confounding factors such as childhood health or risk-taking propensity could explain the association. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.

PubMed

Forslund, Kristoffer; Hildebrand, Falk; Nielsen, Trine; Falony, Gwen; Le Chatelier, Emmanuelle; Sunagawa, Shinichi; Prifti, Edi; Vieira-Silva, Sara; Gudmundsdottir, Valborg; Pedersen, Helle K; Arumugam, Manimozhiyan; Kristiansen, Karsten; Voigt, Anita Yvonne; Vestergaard, Henrik; Hercog, Rajna; Costea, Paul Igor; Kultima, Jens Roat; Li, Junhua; Jørgensen, Torben; Levenez, Florence; Dore, Joël; Nielsen, H Bjørn; Brunak, Søren; Raes, Jeroen; Hansen, Torben; Wang, Jun; Ehrlich, S Dusko; Bork, Peer; Pedersen, Oluf

2015-12-10

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.

Quantifying the causal effects of 20mph zones on road casualties in London via doubly robust estimation.

PubMed

Li, Haojie; Graham, Daniel J

2016-08-01

This paper estimates the causal effect of 20mph zones on road casualties in London. Potential confounders in the key relationship of interest are included within outcome regression and propensity score models, and the models are then combined to form a doubly robust estimator. A total of 234 treated zones and 2844 potential control zones are included in the data sample. The propensity score model is used to select a viable control group which has common support in the covariate distributions. We compare the doubly robust estimates with those obtained using three other methods: inverse probability weighting, regression adjustment, and propensity score matching. The results indicate that 20mph zones have had a significant causal impact on road casualty reduction in both absolute and proportional terms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phenotype definition and development--contributions from Group 7.

PubMed

Wilcox, Marsha A; Paterson, Andrew D

2009-01-01

The papers in Genetic Analysis Workshop 16 Group 7 covered a wide range of topics. The effects of confounder misclassification and selection bias on association results were examined by one group. Another focused on bias introduced by various methods of accounting for treatment effects. Two groups used related methods to derive phenotypic traits. They used different analytic strategies for genetic associations with non-overlapping results (but because they used different sets of single-nucleotide polymorphisms (SNPs) and significance criteria, this is not surprising). Another group relied on the well-characterized definition of type 2 diabetes to show benefits of a novel predictive test. Transmission-ratio distortion was the focus of another paper. The results were extended to show a potential secondary benefit of the test to identify potentially mis-called SNPs. (c) 2009 Wiley-Liss, Inc.

Negative affectivity: moderator or confound in emotional dissonance-outcome relationships?

PubMed

Abraham, R

1999-01-01

This study was an examination of the impact of negative affectivity on relationships between emotional dissonance, job satisfaction, and emotional exhaustion. Negative affectivity is the predisposition to view life in negative terms. Emotional dissonance originates from the conflict between expressed and experienced emotions. In organizations that require the expression of positive emotions, high negative affectivity individuals may experience conflict between expressed, positive emotions and felt, negative emotions. A moderator effect exists when high negative affectivity individuals experience greater job dissatisfaction and emotional exhaustion. Alternatively, negative affectivity may exert a confounding effect through its relationship to both emotional dissonance and its outcomes. Empirical tests showed that negative affectivity moderated the emotional dissonance-job satisfaction relationship and confounded the emotional dissonance-emotional exhaustion relationship.

Do time-invariant confounders explain away the association between job stress and workers' mental health? Evidence from Japanese occupational panel data.

PubMed

Oshio, Takashi; Tsutsumi, Akizumi; Inoue, Akiomi

2015-02-01

It is well known that job stress is negatively related to workers' mental health, but most recent studies have not controlled for unobserved time-invariant confounders. In the current study, we attempted to validate previous observations on the association between job stress and workers' mental health, by removing the effects of unobserved time-invariant confounders. We used data from three to four waves of an occupational Japanese cohort survey, focusing on 31,382 observations of 9741 individuals who participated in at least two consecutive waves. We estimated mean-centered fixed effects models to explain psychological distress in terms of the Kessler 6 (K6) scores (range: 0-24) by eight job stress indicators related to the job demands-control, effort-reward imbalance, and organizational injustice models. Mean-centered fixed effects models reduced the magnitude of the association between jobs stress and K6 scores to 44.8-54.2% of those observed from pooled ordinary least squares. However, the association remained highly significant even after controlling for unobserved time-invariant confounders for all job stress indicators. In addition, alternatively specified models showed the robustness of the results. In all, we concluded that the validity of major job stress models, which link job stress and workers' mental health, was robust, although unobserved time-invariant confounders led to an overestimation of the association. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of diurnal temperature range on human health: a systematic review.

PubMed

Cheng, Jian; Xu, Zhiwei; Zhu, Rui; Wang, Xu; Jin, Liu; Song, Jian; Su, Hong

2014-11-01

Increasing epidemiological studies have shown that a rapid temperature change within 1 day is an independent risk factor for human health. This paper aimed to systematically review the epidemiological evidence on the relationship between diurnal temperature range (DTR) and human health and to propose future research directions. A literature search was conducted in October 2013 using the databases including PubMed, ScienceDirect, and EBSCO. Empirical studies regarding the relationship between DTR and mortality and morbidity were included. Twenty-five relevant studies were identified, among which, 11 investigated the relationship between DTR and mortality and 14 examined the impact of DTR on morbidity. The majority of existing studies reported that DTR was significantly associated with mortality and morbidity, particularly for cardiovascular and respiratory diseases. Notably, compared with adults, the elderly and children were more vulnerable to DTR effects. However, there were some inconsistencies regarding the susceptible groups, lag time, and threshold of DTR. The impact of DTR on human health may be confounded or modified by season, socioeconomic, and educational status. Further research is needed to further confirm the adverse effects of DTR in different geographical locations; examine the effects of DTR on the health of children aged one or under; explore extreme DTR effects on human health; analyze the difference of DTR effects on human health in different locations and the modified effects of potential confounding factors; and develop detailed preventive measures against large DTR, particularly for susceptible groups.

Everything that you have ever been told about assessment center ratings is confounded.

PubMed

Jackson, Duncan J R; Michaelides, George; Dewberry, Chris; Kim, Young-Jae

2016-07-01

Despite a substantial research literature on the influence of dimensions and exercises in assessment centers (ACs), the relative impact of these 2 sources of variance continues to raise uncertainties because of confounding. With confounded effects, it is not possible to establish the degree to which any 1 effect, including those related to exercises and dimensions, influences AC ratings. In the current study (N = 698) we used Bayesian generalizability theory to unconfound all of the possible effects contributing to variance in AC ratings. Our results show that ≤1.11% of the variance in AC ratings was directly attributable to behavioral dimensions, suggesting that dimension-related effects have no practical impact on the reliability of ACs. Even when taking aggregation level into consideration, effects related to general performance and exercises accounted for almost all of the reliable variance in AC ratings. The implications of these findings for recent dimension- and exercise-based perspectives on ACs are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Developing hazelnut tissue culture medium free of ion confounding

USDA-ARS?s Scientific Manuscript database

The general approach for tissue culture medium optimization is to use salts as factors in experimental design and analysis. However, using salts as factors leads to ion confounding, making it difficult to detect the effects of individual ions on particular growth responses. This study focused on tes...

Evaluation in medical education: A topical review of target parameters, data collection tools and confounding factors.

PubMed

Schiekirka, Sarah; Feufel, Markus A; Herrmann-Lingen, Christoph; Raupach, Tobias

2015-01-01

Evaluation is an integral part of education in German medical schools. According to the quality standards set by the German Society for Evaluation, evaluation tools must provide an accurate and fair appraisal of teaching quality. Thus, data collection tools must be highly reliable and valid. This review summarises the current literature on evaluation of medical education with regard to the possible dimensions of teaching quality, the psychometric properties of survey instruments and potential confounding factors. We searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical education and included studies published up until June 30, 2011 as well as articles identified in the "grey literature". RESULTS are presented as a narrative review. We identified four dimensions of teaching quality: structure, process, teacher characteristics, and outcome. Student ratings are predominantly used to address the first three dimensions, and a number of reliable tools are available for this purpose. However, potential confounders of student ratings pose a threat to the validity of these instruments. Outcome is usually operationalised in terms of student performance on examinations, but methodological problems may limit the usability of these data for evaluation purposes. In addition, not all examinations at German medical schools meet current quality standards. The choice of tools for evaluating medical education should be guided by the dimension that is targeted by the evaluation. Likewise, evaluation results can only be interpreted within the context of the construct addressed by the data collection tool that was used as well as its specific confounding factors.

Weekend Effect in Children With Stroke in the Nationwide Inpatient Sample.

PubMed

Adil, Malik M; Vidal, Gabriel; Beslow, Lauren A

2016-06-01

Studies have demonstrated differences in clinical outcomes in adult patients with stroke admitted on weekdays versus weekends. The study's objective was to determine whether a weekend impacts clinical outcomes in children with ischemic stroke and hemorrhagic stroke. Children aged 1 to 18 years admitted to US hospitals from 2002 to 2011 with a primary discharge diagnosis of ischemic stroke or hemorrhagic stroke were identified by International Classification of Disease, 9th Revision, codes. Logistic regression estimated odds ratios and 95% confidence intervals for in-hospital mortality and discharge to a nursing facility among children admitted on weekends (Saturday and Sunday) versus weekdays (Monday to Friday), adjusting for potential confounders. Of 8467 children with ischemic stroke, 28% were admitted on a weekend. Although children admitted on weekends did not have a higher in-hospital mortality rate than those admitted on weekdays (4.1% versus 3.3%; P=0.4), children admitted on weekends had a higher rate of discharge to a nursing facility (25.5% versus 18.6%; P=0.003). After adjusting for age, sex, and confounders, the odds of discharge to a nursing facility remained increased among children admitted on weekends (odds ratio, 1.5; 95% confidence interval, 1.1-1.9; P=0.006). Of 10 919 children with hemorrhagic stroke, 25.3% were admitted on a weekend. Children admitted on weekends had a higher rate of in-hospital mortality (12% versus 8%; P=0.006). After adjusting for age, sex, and confounders, the odds of in-hospital mortality remained higher among children admitted on weekends (odds ratio, 1.4; 95% confidence interval, 1.1-1.9; P=0.04). There seems to be a weekend effect for children with ischemic and hemorrhagic strokes. Quality improvement initiatives should examine this phenomenon prospectively. © 2016 American Heart Association, Inc.

Adjusting for Confounding in Early Postlaunch Settings: Going Beyond Logistic Regression Models.

PubMed

Schmidt, Amand F; Klungel, Olaf H; Groenwold, Rolf H H

2016-01-01

Postlaunch data on medical treatments can be analyzed to explore adverse events or relative effectiveness in real-life settings. These analyses are often complicated by the number of potential confounders and the possibility of model misspecification. We conducted a simulation study to compare the performance of logistic regression, propensity score, disease risk score, and stabilized inverse probability weighting methods to adjust for confounding. Model misspecification was induced in the independent derivation dataset. We evaluated performance using relative bias confidence interval coverage of the true effect, among other metrics. At low events per coefficient (1.0 and 0.5), the logistic regression estimates had a large relative bias (greater than -100%). Bias of the disease risk score estimates was at most 13.48% and 18.83%. For the propensity score model, this was 8.74% and >100%, respectively. At events per coefficient of 1.0 and 0.5, inverse probability weighting frequently failed or reduced to a crude regression, resulting in biases of -8.49% and 24.55%. Coverage of logistic regression estimates became less than the nominal level at events per coefficient ≤5. For the disease risk score, inverse probability weighting, and propensity score, coverage became less than nominal at events per coefficient ≤2.5, ≤1.0, and ≤1.0, respectively. Bias of misspecified disease risk score models was 16.55%. In settings with low events/exposed subjects per coefficient, disease risk score methods can be useful alternatives to logistic regression models, especially when propensity score models cannot be used. Despite better performance of disease risk score methods than logistic regression and propensity score models in small events per coefficient settings, bias, and coverage still deviated from nominal.

Association Between Cardiovascular Risk Factors and Carpal Tunnel Syndrome in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew Steven; Kapellusch, Jay; Merryweather, Andrew S; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Wertsch, Jacqueline; Foster, James; Garg, Arun; Drury, David L

2016-01-01

The aim of the study was to ascertain if cardiovascular (CVD) risk factors are carpal tunnel syndrome (CTS) risk factors. Analysis of pooled baseline data from two large prospective cohort studies (n = 1824) assessed the relationships between a modified Framingham Heart Study CVD risk score both CTS and abnormal nerve conduction study prevalence. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratio and 95% confidence intervals were calculated for individual risk scores. There was a strong relationship between CVD risk score and both CTS and abnormal nerve conduction study after adjustment for confounders, with odds ratios as high as 4.16 and 7.35, respectively. Dose responses were also observed. In this workplace population, there is a strong association between CVD risk scores and both CTS and abnormal nerve conduction study that persisted after controlling for confounders. These data suggest a potentially modifiable disease mechanism.

Are attractive men's faces masculine or feminine? The importance of controlling confounds in face stimuli.

PubMed

DeBruine, Lisa M; Jones, Benedict C; Smith, Finlay G; Little, Anthony C

2010-06-01

Women's preferences for male masculinity are highly variable. Although many researchers explain this variability as reflecting systematic individual differences in how women resolve the tradeoff between the costs and benefits of choosing a masculine partner, others suggest that methodological differences between studies are responsible. A recent study found general femininity preferences for judgments of faces that were manipulated in sexual dimorphism of shape but general masculinity preferences for judgments of faces that were based on perceived masculinity. Using the original stimuli, we replicated these previous results but found equivalent general femininity preferences for both types of faces when nonface confounds in the stimuli (e.g. hairstyle) were eliminated through masking. We conclude that care must be taken to control potential confounds in stimuli and that the influence of nonface cues on preferences for facial masculinity deserves further study.

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Appropriate and inappropriate methods for investigating the "gateway" hypothesis, with a review of the evidence linking prior snus use to later cigarette smoking.

PubMed

Lee, Peter N

2015-03-20

The "gateway hypothesis" usually refers to the possibility that the taking up of habit A, which is considered harmless (or less harmful), may lead to the subsequent taking up of another habit, B, which is considered harmful (or more harmful). Possible approaches to designing and analysing studies to test the hypothesis are discussed. Evidence relating to the use of snus (A) as a gateway for smoking (B) is then evaluated in detail. The importance of having appropriate data available on the sequence of use of A and B and on other potential confounding factors that may lead to the taking up of B is emphasised. Where randomised trials are impractical, the preferred designs include the prospective cohort study in which ever use of A and of B is recorded at regular intervals, and the cross-sectional survey in which time of starting to use A and B is recorded. Both approaches allow time-stratified analytical methods to be used, in which, in each time period, risk of initiating B among never users of B at the start of the interval is compared according to prior use of A. Adjustment in analysis for the potential confounding factors is essential. Of 11 studies of possible relevance conducted in Sweden, Finland or Norway, only one seriously addresses potential confounding by those other factors involved in the initiation of smoking. Furthermore, 5 of the 11 studies are of a design that does not allow proper testing of the gateway hypothesis for various reasons, and the analysis is unsatisfactory, sometimes seriously, in all the remaining six. While better analyses could be attempted for some of the six studies identified as having appropriate design, the issues of confounding remain, and more studies are clearly needed. To obtain a rapid answer, a properly designed cross-sectional survey is recommended.

Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up.

PubMed

Piirtola, Maarit; Kaprio, Jaakko; Kujala, Urho M; Heikkilä, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Ropponen, Annina

2016-08-04

Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day) was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models. Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations. Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow-up. The association was found after adjusting for several confounders, including familial factors. Hence, the results point to the conclusion that education has an independent role in the development of long-term physical inactivity and tailored efforts to promote physical activity among lower educated people would be needed throughout adulthood.

Smoking prevalence and seizure control in Chinese males with epilepsy.

PubMed

Gao, Hui; Sander, Josemir W; Du, Xudong; Chen, Jiani; Zhu, Cairong; Zhou, Dong

2017-08-01

Smoking has a negative effect on most diseases, yet it is under-investigated in people with epilepsy; thus its role is not clear in the general population with epilepsy. We performed a retrospective pilot study on males with epilepsy to determine the smoking rate and its relationship with seizure control using univariate analysis to calculate odds ratios (ORs) and also used a multi-variate logistic regression model. The smoking rate in our sample of 278 individuals was 25.5%, which is lower than the general Chinese population smoking rate among males of 52.1%. We used two classifications: the first classified epilepsy as generalized, or by presumed topographic origin (temporal, frontal, parietal and occipital). The second classified the dominant seizure type of an individual as generalized tonic clonic seizure (GTCS), myoclonic seizure (MS), complex partial seizure (CPS), simple partial seizure (SPS), and secondary GTCS (sGTCS). The univariable analysis of satisfactory seizure control profile and smoking rate in both classifications showed a trend towards a beneficial effect of smoking although most were not statistically significant. Considering medication is an important confounding factor that would largely influence seizure control, we also conducted multi-variable analysis for both classifications with drug numbers and dosage. The result of our model also suggested that smoking is a protective factor. Our findings seem to suggest that smoking could have a potential role in seizure control although confounders need exploration particularly in view of the potential long term health effects. Replication in a much larger sample is needed as well as case control studies to elucidate this issue. Copyright © 2017 Elsevier Inc. All rights reserved.

The associations between family characteristics and depressive symptoms in older adults: a community-based survey in rural China.

PubMed

Gong, Yanhong; Wen, Xiaopiao; Guan, Chaoping; Wang, Zhiqing; Liang, Yuan

2012-08-01

The aim of the current study was to investigate the associations between family characteristics and depressive symptoms, and provide new evidence and recommendations for prevention and intervention in the depressive symptoms of older adults. The study was a cross-sectional survey conducted door-to-door, utilizing a sample of 1,317 individuals aged 60 years and above in rural China. The five family characteristic variables recorded were: living with spouse, living with descendant, support of family members, self-reported family economic status in the previous year, and family-related negative life events that occurred anytime in the past with a continuous psychological effect during the past 12 months. Gender, age, years of schooling, and self-rated physical health status were taken as potential confounders. Univariable and multivariable logistic regression models were used to examine independent effects on depressive symptoms. In addition to the potential confounders, only family-related negative life events, support of family members, and self-reported family economic status had significant effects on depressive symptoms in older adults. Experiencing a family-related negative life event was the most significant variable (OR = 11.70, 95% CI: 7.72-17.73), the second was support of family members (OR = 6.93, 95% CI: 3.26-14.70), while family economic status was less important than support of family members (OR = 2.38, 95% CI: 1.08-5.25). This study, from the perspective of family characteristics on depressive symptoms in older adults, showed a strong correlation between being exposed to harmful family environments and depressive symptoms among the elderly. Efforts to address family risk factors and strengthen family cohesiveness deserve a higher priority, given the importance of these factors, compared with other efforts such as promoting economic development.

Particulate matter air pollution and liver cancer survival.

PubMed

Deng, Huiyu; Eckel, Sandrah P; Liu, Lihua; Lurmann, Frederick W; Cockburn, Myles G; Gilliland, Frank D

2017-08-15

Particulate matter (PM) air pollution exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. Twenty thousand, two hundred and twenty-one California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000 and 2009 were used to examine the effect of exposure to ambient PM with diameter <2.5 μm (PM 2.5 ) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM 2.5 to all-cause and liver cancer-specific mortality linearly and nonlinearly-overall and stratified by stage at diagnosis (local, regional and distant)-adjusting for potential individual and geospatial confounders.PM 2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all-cause mortality HR associated with a 1 standard deviation (5.0 µg/m 3 ) increase in PM 2.5 was 1.18 (95% CI: 1.16-1.20); 1.31 (95% CI:1.26-1.35) for local stage, 1.19 (95% CI:1.14-1.23) for regional stage, and 1.05 (95% CI:1.01-1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer-specific mortality and PM 2.5 were slightly attenuated compared to all-cause mortality, but with the same patterns.Exposure to elevated PM 2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations. © 2017 UICC.

Seasonal and annual changes in soil respiration in relation to soil temperature, water potential and trenching.

PubMed

Lavigne, M B; Foster, R J; Goodine, G

2004-04-01

Soil respiration (rs), soil temperature (Ts) and volumetric soil water content were measured in a balsam fir (Abies balsamea (L.) Mill.) ecosystem from 1998 to 2001. Seasonal variation in root and microbial respiration, and covariation in abiotic factors confounded interpretation of the effects of Ts and soil water potential (Psis) on rs. To minimize the confounding effect of temperature, we analyzed the effect of Psis on rs during the summers of 1998-2000 when changes in Ts were slight. Soil respiration declined 25-50% in response to modest water stress (minimum Psis of -0.6 to -0.2 MPa), and between years, there was substantial variation in the relationship between rs and Psis. In the summer of 2000, 2-m2 plots were subjected to drought for 1 month and other plots were irrigated. The relationship between summertime rs and Psis in the experimental plots was similar to that estimated from the survey data obtained during the same summer. In late spring and early autumn of 2001, 2-m2 trenched and untrenched plots were subjected to drought or exposed to rainfall. It was dry in the early autumn and there was severe soil drying (Psis of -10 MPa in untrenched plots and -2 MPa in trenched plots). In spring, rs in untrenched plots responded more to modest water stress than rs in trenched plots, indicating that root respiration is more sensitive than microbial respiration to water stress at this time of year. The response to abiotic factors differed significantly between spring and autumn in untrenched plots but not in trenched plots, indicating that root activity was greater in early autumn than in late spring, and that roots acclimated to the sustained, severe water stress experienced before and during the autumn.

Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268.

PubMed

Kimoto, Sohei; Bazmi, H Holly; Lewis, David A

2014-09-01

Cognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia. The authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes. GAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes. Deficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia.

Effect of Exposure to Air Pollution on Placental Weight in Isfahan-Iran.

PubMed

Ghasemi-Tehrani, Hatav; Fallah, Setare; Mozafarian, Nafiseh; Miranzadeh, Sareh; Sadeghi, Shokooh; Azidhak, Azam

2017-06-01

Objective: To determine the effect of Air Quality Index (AQI) in the first trimester of pregnancy on birth weight, placental weight, and the ratio of placental weight to the birth weight (pw-bw) in Isfahan. Materials and methods: This cross-sectional study was done on 312 consecutive pregnant women in Beheshti Hospital in Isfahan city in 2013. Information on air pollution was received from the Environmental department of Isfahan. Average exposure to air pollution in the first trimester of pregnancy was calculated for eachpregnant woman. In order to compare quantitative and qualitative variables, analysis of variance (ANOVA), and chi-square were applied. After that, the multiple linear regression analysis was used to assess the association the Air Quality Index (AQI) on birth weight, placental weight and the ratio of pw-bw. Potential confounders including age, baby gender, smoking of husband, maternal BMI, maternal occupation, and education and mother's residential area were considered. A statistical significant association were considered for P-value less than 0.05. Results: The findings showed that there is inverse relationship between exposure to air pollution and placental weight in the first trimester of pregnancy after controlling potential confounders (β = -2.57, p-value = 0.008). The inverse relationship between air pollution and the ratio of pw-bw was found. (β = -0.001, p-value = 0.002). Conclusion: The results of this study suggest that air pollution is associated with newborns' health which in turn is a warning alarm for considering some actions in both sides of reducing the air pollution and teaching the pregnant women about the adverse effects of air pollution on the pregnancy outcomes.

Preconception Maternal Iodine Status Is Positively Associated with IQ but Not with Measures of Executive Function in Childhood

PubMed Central

Robinson, Sian M; Crozier, Sarah R; Miles, Elizabeth A; Gale, Catharine R; Calder, Philip C; Cooper, Cyrus; Inskip, Hazel M; Godfrey, Keith M

2018-01-01

Abstract Background Adverse effects of severe maternal iodine deficiency in pregnancy on fetal brain development are well-established, but the effects of milder deficiency are uncertain. Most studies examine iodine status in pregnancy; less is known about iodine nutrition before conception. Objective We examined relations between maternal preconception iodine status and offspring cognitive function, within a prospective mother-offspring cohort. Methods Maternal iodine status was assessed through the use of the ratio of iodine:creatinine concentrations (I/Cr) in spot urine samples [median (IQR) period before conception 3.3 y (2.2–4.7 y)]. Childhood cognitive function was assessed at age 6–7 y. Full-scale IQ was assessed via the Wechsler Abbreviated Scale of Intelligence, and executive function through the use of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses (n = 654 mother-child dyads) were adjusted for potential confounders including maternal intelligence, education, and breastfeeding duration. Results The median (IQR) urinary iodine concentration was 108.4 µg/L (62.2–167.8 µg/L) and the I/Cr ratio 114 µg/g (76–164 µg/g). The preconception I/Cr ratio was positively associated with child IQ, before and after adjustment for potential confounding influences [β = 0.13 (95% CI: 0.04, 0.21)/SD, P = 0.003]. 8.9% of women had a preconception urinary I/Cr ratio <50 µg/g; compared with those with an I/Cr ratio ≥150 µg/g, the IQ of their offspring was 0.49 (95% CI: 0.79, 0.18) SD lower. There were no associations with the executive function outcomes assessed via CANTAB, before or after adjustment for confounders. Conclusion The positive association between iodine status before conception and child IQ provides some support for demonstrated links between low maternal iodine status in pregnancy and poorer cognitive function reported in other studies. However, given the negative effects on school performance previously observed in children born to iodine-deficient mothers, the lack of associations with measures of executive function in the present study was unexpected. Further data are needed to establish the public health importance of low preconception iodine status. PMID:29767745

Identification and Sensitivity Analysis for Average Causal Mediation Effects with Time-Varying Treatments and Mediators: Investigating the Underlying Mechanisms of Kindergarten Retention Policy.

PubMed

Park, Soojin; Steiner, Peter M; Kaplan, David

2018-06-01

Considering that causal mechanisms unfold over time, it is important to investigate the mechanisms over time, taking into account the time-varying features of treatments and mediators. However, identification of the average causal mediation effect in the presence of time-varying treatments and mediators is often complicated by time-varying confounding. This article aims to provide a novel approach to uncovering causal mechanisms in time-varying treatments and mediators in the presence of time-varying confounding. We provide different strategies for identification and sensitivity analysis under homogeneous and heterogeneous effects. Homogeneous effects are those in which each individual experiences the same effect, and heterogeneous effects are those in which the effects vary over individuals. Most importantly, we provide an alternative definition of average causal mediation effects that evaluates a partial mediation effect; the effect that is mediated by paths other than through an intermediate confounding variable. We argue that this alternative definition allows us to better assess at least a part of the mediated effect and provides meaningful and unique interpretations. A case study using ECLS-K data that evaluates kindergarten retention policy is offered to illustrate our proposed approach.

On Estimation of the Survivor Average Causal Effect in Observational Studies when Important Confounders are Missing Due to Death

PubMed Central

Egleston, Brian L.; Scharfstein, Daniel O.; MacKenzie, Ellen

2008-01-01

We focus on estimation of the causal effect of treatment on the functional status of individuals at a fixed point in time t* after they have experienced a catastrophic event, from observational data with the following features: (1) treatment is imposed shortly after the event and is non-randomized, (2) individuals who survive to t* are scheduled to be interviewed, (3) there is interview non-response, (4) individuals who die prior to t* are missing information on pre-event confounders, (5) medical records are abstracted on all individuals to obtain information on post-event, pre-treatment confounding factors. To address the issue of survivor bias, we seek to estimate the survivor average causal effect (SACE), the effect of treatment on functional status among the cohort of individuals who would survive to t* regardless of whether or not assigned to treatment. To estimate this effect from observational data, we need to impose untestable assumptions, which depend on the collection of all confounding factors. Since pre-event information is missing on those who die prior to t*, it is unlikely that these data are missing at random (MAR). We introduce a sensitivity analysis methodology to evaluate the robustness of SACE inferences to deviations from the MAR assumption. We apply our methodology to the evaluation of the effect of trauma center care on vitality outcomes using data from the National Study on Costs and Outcomes of Trauma Care. PMID:18759833

Effects of heat waves on mortality: effect modification and confounding by air pollutants.

PubMed

Analitis, Antonis; Michelozzi, Paola; D'Ippoliti, Daniela; De'Donato, Francesca; Menne, Bettina; Matthies, Franziska; Atkinson, Richard W; Iñiguez, Carmen; Basagaña, Xavier; Schneider, Alexandra; Lefranc, Agnès; Paldy, Anna; Bisanti, Luigi; Katsouyanni, Klea

2014-01-01

Heat waves and air pollution are both associated with increased mortality. Their joint effects are less well understood. We explored the role of air pollution in modifying the effects of heat waves on mortality, within the EuroHEAT project. Daily mortality, meteorologic, and air pollution data from nine European cities for the years 1990-2004 were assembled. We defined heat waves by taking both intensity and duration into account. The city-specific effects of heat wave episodes were estimated using generalized estimating equation models, adjusting for potential confounders with and without inclusion of air pollutants (particles, ozone, nitrogen dioxide, sulphur dioxide, carbon monoxide). To investigate effect modification, we introduced an interaction term between heat waves and each single pollutant in the models. Random effects meta-analysis was used to summarize the city-specific results. The increase in the number of daily deaths during heat wave episodes was 54% higher on high ozone days compared with low, among people age 75-84 years. The heat wave effect on high PM10 days was increased by 36% and 106% in the 75-84 year and 85+ year age groups, respectively. A similar pattern was observed for effects on cardiovascular mortality. Effect modification was less evident for respiratory mortality, although the heat wave effect itself was greater for this cause of death. The heat wave effect was smaller (15-30%) after adjustment for ozone or PM10. The heat wave effect on mortality was larger during high ozone or high PM10 days. When assessing the effect of heat waves on mortality, lack of adjustment for ozone and especially PM10 overestimates effect parameters. This bias has implications for public health policy.

Effects of plant diversity, community composition and environmental parameters on productivity in montane European grasslands.

PubMed

Kahmen, Ansgar; Perner, Jörg; Audorff, Volker; Weisser, Wolfgang; Buchmann, Nina

2005-02-01

In the past years, a number of studies have used experimental plant communities to test if biodiversity influences ecosystem functioning such as productivity. It has been argued, however, that the results achieved in experimental studies may have little predictive value for species loss in natural ecosystems. Studies in natural ecosystems have been equivocal, mainly because in natural ecosystems differences in diversity are often confounded with differences in land use history or abiotic parameters. In this study, we investigated the effect of plant diversity on ecosystem functioning in semi-natural grasslands. In an area of 10x20 km, we selected 78 sites and tested the effects of various measures of diversity and plant community composition on productivity. We separated the effects of plant diversity on ecosystem functioning from potentially confounding effects of community composition, management or environmental parameters, using multivariate statistical analyses. In the investigated grasslands, simple measures of biodiversity were insignificant predictors of productivity. However, plant community composition explained productivity very well (R2=0.31) and was a better predictor than environmental variables (soil and site characteristics) or management regime. Thus, complex measures such as community composition and structure are important drivers for ecosystem functions in semi-natural grasslands. Furthermore, our data show that it is difficult to extrapolate results from experimental studies to semi-natural ecosystems, although there is a need to investigate natural ecosystems to fully understand the relationship of biodiversity and ecosystem functioning.

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

PubMed Central

Zeka, Ariana; Melly, Steve J; Schwartz, Joel

2008-01-01

Background Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors. Methods A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes (birth weight, small for gestational age and preterm births), in a two-level hierarchical model. Results We found effects of both individual (education, race, prenatal care index) and area-based (median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income. Conclusion Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health. PMID:19032747

A Comparison of Agent-Based Models and the Parametric G-Formula for Causal Inference.

PubMed

Murray, Eleanor J; Robins, James M; Seage, George R; Freedberg, Kenneth A; Hernán, Miguel A

2017-07-15

Decision-making requires choosing from treatments on the basis of correctly estimated outcome distributions under each treatment. In the absence of randomized trials, 2 possible approaches are the parametric g-formula and agent-based models (ABMs). The g-formula has been used exclusively to estimate effects in the population from which data were collected, whereas ABMs are commonly used to estimate effects in multiple populations, necessitating stronger assumptions. Here, we describe potential biases that arise when ABM assumptions do not hold. To do so, we estimated 12-month mortality risk in simulated populations differing in prevalence of an unknown common cause of mortality and a time-varying confounder. The ABM and g-formula correctly estimated mortality and causal effects when all inputs were from the target population. However, whenever any inputs came from another population, the ABM gave biased estimates of mortality-and often of causal effects even when the true effect was null. In the absence of unmeasured confounding and model misspecification, both methods produce valid causal inferences for a given population when all inputs are from that population. However, ABMs may result in bias when extrapolated to populations that differ on the distribution of unmeasured outcome determinants, even when the causal network linking variables is identical. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Event-related potentials to event-related words: grammatical class and semantic attributes in the representation of knowledge.

PubMed

Barber, Horacio A; Kousta, Stavroula-Thaleia; Otten, Leun J; Vigliocco, Gabriella

2010-05-21

A number of recent studies have provided contradictory evidence on the question of whether grammatical class plays a role in the neural representation of lexical knowledge. Most of the previous studies comparing the processing of nouns and verbs, however, confounded word meaning and grammatical class by comparing verbs referring to actions with nouns referring to objects. Here, we recorded electrical brain activity from native Italian speakers reading single words all referring to events (e.g., corsa [the run]; correre [to run]), thus avoiding confounding nouns and verbs with objects and actions. We manipulated grammatical class (noun versus verb) as well as semantic attributes (motor versus sensory events). Activity between 300 and 450ms was more negative for nouns than verbs, and for sensory than motor words, over posterior scalp sites. These grammatical class and semantic effects were not dissociable in terms of latency, duration, or scalp distribution. In a later time window (450-110ms) and at frontal regions, grammatical class and semantic effects interacted; motor verbs were more positive than the other three word categories. We suggest that the lack of a temporal and topographical dissociation between grammatical class and semantic effects in the time range of the N400 component is compatible with an account in which both effects reflect the same underlying process related to meaning retrieval, and we link the later effect with working memory operations associated to the experimental task. Copyright 2010 Elsevier B.V. All rights reserved.

Five Steps to Successfully Implement and Evaluate Propensity Score Matching in Clinical Research Studies.

PubMed

Staffa, Steven J; Zurakowski, David

2018-01-09

In clinical research, the gold standard level of evidence is the randomized controlled trial (RCT). The availability of nonrandomized retrospective data is growing; however, a primary concern of analyzing such data is comparability of the treatment groups with respect to confounding variables. Propensity score matching (PSM) aims to equate treatment groups with respect to measured baseline covariates to achieve a comparison with reduced selection bias. It is a valuable statistical methodology that mimics the RCT, and it may create an "apples to apples" comparison while reducing bias due to confounding. PSM can improve the quality of anesthesia research and broaden the range of research opportunities. PSM is not necessarily a magic bullet for poor-quality data, but rather may allow the researcher to achieve balanced treatment groups similar to a RCT when high-quality observational data are available. PSM may be more appealing than the common approach of including confounders in a regression model because it allows for a more intuitive analysis of a treatment effect between 2 comparable groups.We present 5 steps that anesthesiologists can use to successfully implement PSM in their research with an example from the 2015 Pediatric National Surgical Quality Improvement Program: a validated, annually updated surgery and anesthesia pediatric database. The first step of PSM is to identify its feasibility with regard to the data at hand and ensure availability of data on any potential confounders. The second step is to obtain the set of propensity scores from a logistic regression model with treatment group as the outcome and the balancing factors as predictors. The third step is to match patients in the 2 treatment groups with similar propensity scores, balancing all factors. The fourth step is to assess the success of the matching with balance diagnostics, graphically or analytically. The fifth step is to apply appropriate statistical methodology using the propensity-matched data to compare outcomes among treatment groups.PSM is becoming an increasingly more popular statistical methodology in medical research. It often allows for improved evaluation of a treatment effect that may otherwise be invalid due to a lack of balance between the 2 treatment groups with regard to confounding variables. PSM may increase the level of evidence of a study and in turn increases the strength and generalizability of its results. Our step-by-step approach provides a useful strategy for anesthesiologists to implement PSM in their future research.

The development of a modified spectral ripple test.

PubMed

Aronoff, Justin M; Landsberger, David M

2013-08-01

Poor spectral resolution can be a limiting factor for hearing impaired listeners, particularly for complex listening tasks such as speech understanding in noise. Spectral ripple tests are commonly used to measure spectral resolution, but these tests contain a number of potential confounds that can make interpretation of the results difficult. To measure spectral resolution while avoiding those confounds, a modified spectral ripple test with dynamically changing ripples was created, referred to as the spectral-temporally modulated ripple test (SMRT). This paper describes the SMRT and provides evidence that it is sensitive to changes in spectral resolution.

The Value of Response Times in Item Response Modeling

ERIC Educational Resources Information Center

Molenaar, Dylan

2015-01-01

A new and very interesting approach to the analysis of responses and response times is proposed by Goldhammer (this issue). In his approach, differences in the speed-ability compromise within respondents are considered to confound the differences in ability between respondents. These confounding effects of speed on the inferences about ability can…

The effects of sleep duration on the incidence of cardiovascular events among middle-aged male workers in Japan.

PubMed

Hamazaki, Yuko; Morikawa, Yuko; Nakamura, Koshi; Sakurai, Masaru; Miura, Katsuyuki; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki

2011-09-01

Although previous epidemiological studies have investigated the relationship between sleep duration and various cardiovascular events, the results have been inconsistent. Accordingly, we conducted a follow-up survey to investigate the relationship between sleep duration and cardiovascular events among male workers, accounting for occupational factors that might confound the true relationship. A total of 2282 male employees aged 35-54 years based in a factory in Japan were followed for 14 years. The risk of cardiovascular events was compared among 4 groups stratified based on sleep duration at baseline (<6, 6-6.9, 7-7.9, and ≥8 hours). Cardiovascular events included stroke, coronary events and sudden cardiac death. The hazard ratios for events were calculated using a Cox proportional hazards model, with the 7-7.9-hour group serving as a reference. The model was adjusted for potential confounders including traditional cardiovascular risk factors and working characteristics. During 14 years of follow-up, 64 cardiovascular events were recorded including 30 strokes, 27 coronary events and 7 sudden cardiac deaths. After adjustment for possible confounders, the hazard ratios for cardiovascular and coronary events in the <6-hour group were 3.49 [95% confidence interval (95% CI) 1.30-9.40] and 4.95 (95% CI 1.31-18.73), respectively. There was no significant increment in the risk of stroke for any sleep duration groups. Short sleep duration (<6 hours) was a significant risk factor for coronary events in a Japanese male working population.

Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy.

PubMed

Hooijmans, M T; Damon, B M; Froeling, M; Versluis, M J; Burakiewicz, J; Verschuuren, J J G M; Niks, E H; Webb, A G; Kan, H E

2015-11-01

Diffusion tensor imaging (DTI) is a popular method to assess differences in fiber organization in diseased and healthy muscle tissue. Previous work has shown that muscle DTI measurements depend on signal-to-noise ratio (SNR), %fat, and tissue T2. The goal of this study was to evaluate the potential biasing effects of these factors on skeletal muscle DTI data in patients with Duchenne Muscular Dystrophy (DMD). MR images were obtained of the right lower leg of 21 DMD patients and 12 healthy controls on a Philips 3T system. DTI measurements were combined with quantitative in-vivo measures of mean water T2, %fat and SNR to evaluate their effect on DTI parameter estimation. All outcome measures were determined within ROIs drawn for six lower leg muscles. Between group analysis, using all ROIs, revealed a significantly elevated FA in the GCL, SOL and PER muscles (p<0.05) and an increased mean diffusivity (p<0.05) and λ3 (p<0.05) in the TA muscle of DMD patients. In-vivo evaluation of the individual confounders showed behaviour in line with predictions from previous simulation work. To account for these confounders, subsequent analysis used only ROIs with SNR greater than 20. With this criterion we found significantly greater MD in the TA muscle of DMD patient (p<0.009) and λ3 in the TA and GCL muscles (p<0.001) of DMD patients, but no differences in FA. As both increased %fat and lower SNR are expected to reduce the apparent MD and λ3, these between-group differences are likely due to pathophysiology. However, the increased FA, observed when using all ROIs, likely reflects the effect of low SNR and %fat on the DTI parameter estimation. These findings suggest that measuring mean water T2, %fat and SNR is essential to ascribe changes in DTI measures to intrinsic diffusion changes or to confounding influences. Copyright © 2015 John Wiley & Sons, Ltd.

Social network effects in contraceptive behavior among adolescents.

PubMed

Ali, Mir M; Amialchuk, Aliaksandr; Dwyer, Debra S

2011-10-01

To quantify empirically the role of peer social networks in contraceptive behavior among adolescents. Using longitudinal data from a nationally representative sample of adolescents, the authors use a multivariate structural model with school-level fixed effects to account for the problems of contextual effects, correlated effects, and peer selection to reduce the potential impact of biases from the estimates of peer influence. The peer group measures are drawn not only from the nominations of close friends but also from classmates. Contraception use among the peer groups was constructed using the peers' own reports of their contraceptive behavior. Controlling for parental characteristics and other demographic variables, the authors find that a 10% increase in the proportion of classmates who use contraception increases the likelihood of individual contraception use by approximately 5%. They also find evidence that the influence of close friends diminishes after accounting for unobserved environmental confounders. The findings of this study support the findings in the literature that peer effects are important determinants of contraception use even after controlling for potential biases in the data. Effective policy aimed at increasing contraception use among adolescents should consider these peer effects.

Effects of bilingualism on vocabulary, executive functions, age of dementia onset, and regional brain structure.

PubMed

Gasquoine, Philip Gerard

2016-11-01

To review the current literature on the effects of bilingualism on vocabulary, executive functions, age of dementia onset, and regional brain structure. PubMed and PsycINFO databases were searched (from January 1999 to present) for relevant original research and review articles on bilingualism (but not multilingualism) paired with each target neuropsychological variable published in English. A qualitative review of these articles was conducted. It has long been known that mean scores of bilinguals fall below those of monolinguals on vocabulary and other language, but not visual-perceptual, format cognitive tests. Contemporary studies that have reported higher mean scores for bilinguals than monolinguals on executive function task-switching or inhibition tasks have not always been replicated, leading to concerns of publication bias, statistical flaws, and failures to match groups on potentially confounding variables. Studies suggesting the onset of Alzheimer's disease occurred about 4 years later for bilinguals versus monolinguals have not been confirmed in longitudinal, cohort, community-based, incidence studies that have used neuropsychological testing and diagnostic criteria to establish an age of dementia diagnosis. Neuroimaging studies of regional gray and white matter volume in bilinguals versus monolinguals show inconsistencies in terms of both the regions of difference and the nature of the difference. Resolving inconsistencies in the behavioral data is necessary before searching in the brain for neuroanatomical correlation. Comparisons of balanced versus language-dominant groups within the same ethnoculture combined with objective measurement of bilingualism could better match groups on potentially confounding variables. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Entorhinal Cortex Volume in Antipsychotic-naïve Schizophrenia.

PubMed

Jose, Sam P; Sharma, Eesha; Narayanaswamy, Janardhanan C; Rajendran, Vishnurajan; Kalmady, Sunil V; Rao, Naren P; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2012-04-01

Entorhinal cortex (ERC), a multimodal sensory relay station for the hippocampus, is critically involved in learning, emotion, and novelty detection. One of the pathogenetic mechanistic bases in schizophrenia is proposed to involve aberrant information processing in the ERC. Several studies have looked at cytoarchitectural and morphometric changes in the ERC, but results have been inconsistent possibly due to the potential confounding effects of antipsychotic treatment. In this study, we have examined the entorhinal cortex volume in antipsychotic-naïve schizophrenia patients (n=40; M:F=22:18) in comparison with age, sex, and handedness, matched (as a group) with healthy subjects (n=42; M:F=25:17) using a valid method. 3-Tesla MR images with 1-mm sections were used and the data was analyzed using the SPSS software. Female schizophrenia patients (1.25±0.22 mL) showed significant volume deficit in the right ERC in comparison with female healthy controls (1.45±0.34 mL) (F=4.9; P=0.03), after controlling for the potential confounding effects of intracranial volume. However, male patients did not differ from male controls. The left ERC volume did not differ between patients and controls. Consistent with the findings of a few earlier studies we found a reduction in the right ERC volume in patients. However, this was limited to women. Contextually, our study finding supports the role for ERC deficit in schizophrenia pathogenesis - perhaps mediated through aberrant novelty detection. Sex-differential observation of ERC volume deficit in schizophrenia needs further studies.

Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

PubMed

Pouwels, K B; Van Kleef, E; Vansteelandt, S; Batra, R; Edgeworth, J D; Smieszek, T; Robotham, J V

2017-05-01

Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature. Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes. Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Burden of potentially pathologic copy number variants is higher in children with isolated congenital heart disease and significantly impairs covariate-adjusted transplant-free survival.

PubMed

Kim, Daniel Seung; Kim, Jerry H; Burt, Amber A; Crosslin, David R; Burnham, Nancy; Kim, Cecilia E; McDonald-McGinn, Donna M; Zackai, Elaine H; Nicolson, Susan C; Spray, Thomas L; Stanaway, Ian B; Nickerson, Deborah A; Heagerty, Patrick J; Hakonarson, Hakon; Gaynor, J William; Jarvik, Gail P

2016-04-01

Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival. These cases are derived from a prospective cohort of patients with nonsyndromic CHD (n = 422) identified before first surgery. Healthy pediatric controls (n = 500) were obtained from the electronic Medical Records and Genetic Epidemiology Network, and CNV frequency was contrasted for CHD cases and controls. CNVs were determined algorithmically; subsequently screened for >95% overlap between 2 methods, size (>300 kb), quality score, overlap with a gene, and novelty (absent from databases of known, benign CNVs); and separately validated by quantitative polymerase chain reaction. Survival likelihoods for cases were calculated using Cox proportional hazards modeling to evaluate the joint effect of CNV burden and known confounders on transplant-free survival. Children with nonsyndromic CHD had a higher burden of potentially pathogenic CNVs compared with pediatric controls (12.1% vs 5.0%; P = .00016). Presence of a CNV was associated with significantly decreased transplant-free survival after surgery (hazard ratio, 3.42; 95% confidence interval, 1.66-7.09; P = .00090) with confounder adjustment. We confirm that children with isolated CHD have a greater burden of rare/large CNVs. We report a novel finding that these CNVs are associated with an adjusted 2.55-fold increased risk of death or transplant. These data suggest that CNV burden is an important modifier of survival after surgery for CHD. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Effects of bilingualism on white matter integrity in older adults.

PubMed

Anderson, John A E; Grundy, John G; De Frutos, Jaisalmer; Barker, Ryan M; Grady, Cheryl; Bialystok, Ellen

2018-02-15

Bilingualism can delay the onset of dementia symptoms and has thus been characterized as a mechanism for cognitive or brain reserve, although the origin of this reserve is unknown. Studies with young adults generally show that bilingualism is associated with a strengthening of white matter, but there is conflicting evidence for how bilingualism affects white matter in older age. Given that bilingualism has been shown to help stave off the symptoms of dementia by up to four years, it is crucial that we clarify the mechanism underlying this reserve. The current study uses diffusion tensor imaging (DTI) to compare monolinguals and bilinguals while carefully controlling for potential confounds (e.g., I.Q., MMSE, and demographic variables). We show that group differences in Fractional Anisotropy (FA) and Radial Diffusivity (RD) arise from multivariable interactions not adequately controlled for by sequential bivariate testing. After matching and statistically controlling for confounds, bilinguals still had greater axial diffusivity (AD) in the left superior longitudinal fasciculus than monolingual peers, supporting a neural reserve account for healthy older bilinguals. Copyright © 2017 Elsevier Inc. All rights reserved.

The influence of fundamental frequency on perceived duration in spectrally comparable sounds

PubMed Central

Aalto, Daniel; Simko, Juraj; Vainio, Martti

2017-01-01

The perceived duration of a sound is affected by its fundamental frequency and intensity: higher sounds are judged to be longer, as are sounds with greater intensity. Since increasing intensity lengthens the perceived duration of the auditory object, and increasing the fundamental frequency increases the sound’s perceived loudness (up to ca. 3 kHz), frequency modulation of duration could be potentially explained by a confounding effect where the primary cause of the modulation would be variations in intensity. Here, a series of experiments are described that were designed to disentangle the contributions of fundamental frequency, intensity, and duration to perceived loudness and duration. In two forced-choice tasks, participants judged duration and intensity differences between two sounds varying simultaneously in intensity, fundamental frequency, fundamental frequency gliding range, and duration. The results suggest that fundamental frequency and intensity each have an impact on duration judgments, while frequency gliding range did not influence the present results. We also demonstrate that the modulation of perceived duration by sound fundamental frequency cannot be fully explained by the confounding relationship between frequency and intensity. PMID:28879063

Limitations of a metabolic network-based reverse ecology method for inferring host-pathogen interactions.

PubMed

Takemoto, Kazuhiro; Aie, Kazuki

2017-05-25

Host-pathogen interactions are important in a wide range of research fields. Given the importance of metabolic crosstalk between hosts and pathogens, a metabolic network-based reverse ecology method was proposed to infer these interactions. However, the validity of this method remains unclear because of the various explanations presented and the influence of potentially confounding factors that have thus far been neglected. We re-evaluated the importance of the reverse ecology method for evaluating host-pathogen interactions while statistically controlling for confounding effects using oxygen requirement, genome, metabolic network, and phylogeny data. Our data analyses showed that host-pathogen interactions were more strongly influenced by genome size, primary network parameters (e.g., number of edges), oxygen requirement, and phylogeny than the reserve ecology-based measures. These results indicate the limitations of the reverse ecology method; however, they do not discount the importance of adopting reverse ecology approaches altogether. Rather, we highlight the need for developing more suitable methods for inferring host-pathogen interactions and conducting more careful examinations of the relationships between metabolic networks and host-pathogen interactions.

The influence of fundamental frequency on perceived duration in spectrally comparable sounds.

PubMed

Dawson, Caitlin; Aalto, Daniel; Simko, Juraj; Vainio, Martti

2017-01-01

The perceived duration of a sound is affected by its fundamental frequency and intensity: higher sounds are judged to be longer, as are sounds with greater intensity. Since increasing intensity lengthens the perceived duration of the auditory object, and increasing the fundamental frequency increases the sound's perceived loudness (up to ca. 3 kHz), frequency modulation of duration could be potentially explained by a confounding effect where the primary cause of the modulation would be variations in intensity. Here, a series of experiments are described that were designed to disentangle the contributions of fundamental frequency, intensity, and duration to perceived loudness and duration. In two forced-choice tasks, participants judged duration and intensity differences between two sounds varying simultaneously in intensity, fundamental frequency, fundamental frequency gliding range, and duration. The results suggest that fundamental frequency and intensity each have an impact on duration judgments, while frequency gliding range did not influence the present results. We also demonstrate that the modulation of perceived duration by sound fundamental frequency cannot be fully explained by the confounding relationship between frequency and intensity.

Combating Unmeasured Confounding in Cross-Sectional Studies: Evaluating Instrumental-Variable and Heckman Selection Models

PubMed Central

DeMaris, Alfred

2014-01-01

Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904

Who really gets strep sore throat? Confounding and effect modification of a time-varying exposure on recurrent events.

PubMed

Follmann, Dean; Huang, Chiung-Yu; Gabriel, Erin

2016-10-30

Unmeasured confounding is the fundamental obstacle to drawing causal conclusions about the impact of an intervention from observational data. Typically, covariates are measured to eliminate or ameliorate confounding, but they may be insufficient or unavailable. In the special setting where a transient intervention or exposure varies over time within each individual and confounding is time constant, a different tack is possible. The key idea is to condition on either the overall outcome or the proportion of time in the intervention. These measures can eliminate the unmeasured confounding either by conditioning or by use of a proxy covariate. We evaluate existing methods and develop new models from which causal conclusions can be drawn from such observational data even if no baseline covariates are measured. Our motivation for this work was to determine the causal effect of Streptococcus bacteria in the throat on pharyngitis (sore throat) in Indian schoolchildren. Using our models, we show that existing methods can be badly biased and that sick children who are rarely colonized have a high probability that the Streptococcus bacteria are causing their disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

The homicidol effect: investigating murder as a fitness signal.

PubMed

Dahlén, Micael; Söderlund, Magnus

2012-01-01

This article extends homicide adaptation theory by investigating signal effects of a murder. In two experiments (N = 299 and N = 161) participants reported their perceptions of a described person. The first study manipulated the information about the person (including or excluding a single sentence stating that the person has committed a murder) and stimulus person/observer sex match (same vs. opposite sex). Results suggest that murder functions as a signal of the described person's fitness that enhances observers' evaluations and inclination to interact with the person. Opposite-sex observers evaluate the murderer's intent more favorably than same-sex observers, but these evaluations of intent produce differential (positive vs. negative) effects between the two groups. The second study replicated the findings and ruled out potential confounds.

Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease

PubMed Central

2013-01-01

There is a substantial amount of evidence from experimental parkinsonian models to show the neuroprotective effects of monoamine oxidase-B (MAOB) inhibitors. They have been studied for their potential disease-modifying effects in Parkinson’s disease (PD) for over 20 years in various clinical trials. This review provides a summary of the clinical trials and discusses the implications of their results in the context of disease-modification in PD. Earlier clinical trials on selegiline were confounded by symptomatic effects of this drug. Later clinical trials on rasagiline using delayed-start design provide newer insights in disease-modification in PD but success in achieving the aims of this strategy remain elusive due to obstacles, some of which may be insurmountable. PMID:24011391

Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways

PubMed Central

Burgess, Stephen; Daniel, Rhian M; Butterworth, Adam S; Thompson, Simon G

2015-01-01

Background: Mendelian randomization uses genetic variants, assumed to be instrumental variables for a particular exposure, to estimate the causal effect of that exposure on an outcome. If the instrumental variable criteria are satisfied, the resulting estimator is consistent even in the presence of unmeasured confounding and reverse causation. Methods: We extend the Mendelian randomization paradigm to investigate more complex networks of relationships between variables, in particular where some of the effect of an exposure on the outcome may operate through an intermediate variable (a mediator). If instrumental variables for the exposure and mediator are available, direct and indirect effects of the exposure on the outcome can be estimated, for example using either a regression-based method or structural equation models. The direction of effect between the exposure and a possible mediator can also be assessed. Methods are illustrated in an applied example considering causal relationships between body mass index, C-reactive protein and uric acid. Results: These estimators are consistent in the presence of unmeasured confounding if, in addition to the instrumental variable assumptions, the effects of both the exposure on the mediator and the mediator on the outcome are homogeneous across individuals and linear without interactions. Nevertheless, a simulation study demonstrates that even considerable heterogeneity in these effects does not lead to bias in the estimates. Conclusions: These methods can be used to estimate direct and indirect causal effects in a mediation setting, and have potential for the investigation of more complex networks between multiple interrelated exposures and disease outcomes. PMID:25150977

Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study.

PubMed

de Keyser, Catherine E; Leening, Maarten J G; Romio, Silvana A; Jukema, J Wouter; Hofman, Albert; Ikram, M Arfan; Franco, Oscar H; Stijnen, Theo; Stricker, Bruno H

2014-11-01

When studying the causal effect of drug use in observational data, marginal structural modeling (MSM) can be used to adjust for time-dependent confounders that are affected by previous treatment. The objective of this study was to compare traditional Cox proportional hazard models (with and without time-dependent covariates) with MSM to study causal effects of time-dependent drug use. The example of primary prevention of cardiovascular disease (CVD) with statins was examined using up to 17.7 years of follow-up from 4,654 participants of the observational prospective population-based Rotterdam Study. In the MSM model, the weight was based on measurements of established cardiovascular risk factors and co-morbidity. In general, we could not demonstrate important differences in results from the Cox models and MSM. Results from analysis on duration of statin use suggested that substantial residual confounding by indication was not accounted for during the period shortly after statin initiation. In conclusion, although on theoretical grounds MSM is an elegant technique, lack of data on the precise time-dependent confounders, such as indication of treatment or other considerations of the prescribing physician jeopardizes the calculation of valid weights. Confounding remains a hurdle in observational effectiveness research on preventive drugs with a multitude of prescription determinants.

Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis.

PubMed

Atassi, Nazem; Cudkowicz, Merit E; Schoenfeld, David A

2011-07-01

A few studies suggest that non-invasive ventilation (1) and gastric tube (G-tube) may have a positive impact on survival but the effect on functional decline is unclear. Confounding by indication may have produced biased estimates of the benefit seen in some of these retrospective studies. The objective of this study was to evaluate the effects of G-tube and NIV on survival and functional decline using advanced statistical models that adjust for confounding by indications. A database of 331 subjects enrolled in previous clinical trials in ALS was available for analysis. Marginal structural models (MSM) were used to compare the mortality hazards and ALSFRS-R slopes between treatment and non-treatment groups, after adjusting for confounding by indication. Results showed that the placement of a G-tube was associated with an additional 1.42 units/month decline in the ALSFRS-R slope (p < 0.0001) and increased mortality hazard of 0.28 (p = 0.02). The use of NIV had no significant effect on ALSFRS-R decline or mortality. In conclusion, marginal structural models can be used to adjust for confounding by indication in retrospective ALS studies. G-tube placement could be followed by a faster rate of functional decline and increased mortality. Our results may suffer from some of the limitations of retrospective analyses.

How multiple causes combine: independence constraints on causal inference.

PubMed

Liljeholm, Mimi

2015-01-01

According to the causal power view, two core constraints-that causes occur independently (i.e., no confounding) and influence their effects independently-serve as boundary conditions for causal induction. This study investigated how violations of these constraints modulate uncertainty about the existence and strength of a causal relationship. Participants were presented with pairs of candidate causes that were either confounded or not, and that either interacted or exerted their influences independently. Consistent with the causal power view, uncertainty about the existence and strength of causal relationships was greater when causes were confounded or interacted than when unconfounded and acting independently. An elemental Bayesian causal model captured differences in uncertainty due to confounding but not those due to an interaction. Implications of distinct sources of uncertainty for the selection of contingency information and causal generalization are discussed.

Vehicle year and the risk of car crash injury

PubMed Central

Blows, S; Ivers, R; Woodward, M; Connor, J; Ameratunga, S; Norton, R

2003-01-01

Objective: To quantify the association between vehicle age and risk of car crash injury. Design and setting: Data from a population based case-control study conducted in the Auckland region in 1998/99 was used to examine the adjusted risk of car crash injury or death due to vehicle age, after controlling for a range of known confounders. Cases were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and controls were randomly selected cars on Auckland roads. The drivers of the 571 case vehicles and 588 control vehicles completed a structured interview. Main outcome measure: Hospitalisation or death of a vehicle occupant due to car crash injury. Results: Vehicles constructed before 1984 had significantly greater chance of being involved in an injury crash than those constructed after 1994 (odds ratio 2.88, 95% confidence interval (CI) 1.20 to 6.91), after adjustment for potential confounders. There was also a trend for increasing crash risk with each one year increase in vehicle age after adjustment for potential confounders (odds ratio 1.05, 95% CI 0.99 to 1.11; p = 0.09). Conclusion: This study quantifies the increased risk of car crash injury associated with older vehicle year and confirms this as an important public health issue. PMID:14693899

Vehicle year and the risk of car crash injury.

PubMed

Blows, S; Ivers, R Q; Woodward, M; Connor, J; Ameratunga, S; Norton, R

2003-12-01

To quantify the association between vehicle age and risk of car crash injury. Data from a population based case-control study conducted in the Auckland region in 1998/99 was used to examine the adjusted risk of car crash injury or death due to vehicle age, after controlling for a range of known confounders. Cases were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and controls were randomly selected cars on Auckland roads. The drivers of the 571 case vehicles and 588 control vehicles completed a structured interview. Hospitalisation or death of a vehicle occupant due to car crash injury. Vehicles constructed before 1984 had significantly greater chance of being involved in an injury crash than those constructed after 1994 (odds ratio 2.88, 95% confidence interval (CI) 1.20 to 6.91), after adjustment for potential confounders. There was also a trend for increasing crash risk with each one year increase in vehicle age after adjustment for potential confounders (odds ratio 1.05, 95% CI 0.99 to 1.11; p = 0.09). This study quantifies the increased risk of car crash injury associated with older vehicle year and confirms this as an important public health issue.

Longitudinal Monitoring of Patients With Chronic Low Back Pain During Physical Therapy Treatment Using the STarT Back Screening Tool.

PubMed

Medeiros, Flávia Cordeiro; Costa, Leonardo Oliveira Pena; Added, Marco Aurélio Nemitalla; Salomão, Evelyn Cassia; Costa, Lucíola da Cunha Menezes

2017-05-01

Study Design Preplanned secondary analysis of a randomized clinical trial. Background The STarT Back Screening Tool (SBST) was developed to screen and to classify patients with low back pain into subgroups for the risk of having a poor prognosis. However, this classification at baseline does not take into account variables that can influence the prognosis during treatment or over time. Objectives (1) To investigate the changes in risk subgroup measured by the SBST over a period of 6 months, and (2) to assess the long-term predictive ability of the SBST when administered at different time points. Methods Patients with chronic nonspecific low back pain (n = 148) receiving physical therapy care as part of a randomized trial were analyzed. Pain intensity, disability, global perceived effect, and the SBST were collected at baseline, 5 weeks, 3 months, and 6 months. Changes in SBST risk classification were calculated. Hierarchical linear regression models adjusted for potential confounders were built to analyze the predictive capabilities of the SBST when administered at different time points. Results A large proportion of patients (60.8%) changed their risk subgroup after receiving physical therapy care. The SBST improved the prediction for all 6-month outcomes when using the 5-week risk subgroup and the difference between baseline and 5-week subgroup, after controlling for potential confounders. The SBST at baseline did not improve the predictive ability of the models after adjusting for confounders. Conclusion This study shows that many patients change SBST risk subgroup after receiving physical therapy care, and that the predictive ability of the SBST in patients with chronic low back pain increases when administered at different time points. Level of Evidence Prognosis, 2b. J Orthop Sports Phys Ther 2017;47(5):314-323. Epub 29 Mar 2017. doi:10.2519/jospt.2017.7199.

Reanalysis of mortality from lung cancer among diatomaceous earth industry workers, with consideration of potential confounding by asbestos exposure.

PubMed Central

Checkoway, H; Heyer, N J; Demers, P A; Gibbs, G W

1996-01-01

OBJECTIVE: To evaluate the potential for confounding from asbestos exposure, primarily chrysotile, on the relation between crystalline silica and mortality from lung cancer among diatomaceous earth (diatomite) workers. METHODS: A reanalysis of a cohort mortality study of diatomite workers was performed to take into account quantitative estimates of asbestos exposure. The reanalysis was limited to a subset of the original cohort, comprising 2266 white men for whom asbestos exposure could be reconstructed with greatest confidence. Comparisons between mortality from lung cancer (standardised mortality ratios (SMR)) were made between rates for 1942-87 for United States white men, and workers cross classified according to cumulative exposures to crystalline silica and asbestos. Comparisons of internal rates, involving Poisson regression modeling, were conducted for exposure to crystalline silica, with and without adjustment for asbestos exposure. Exposures were lagged by 15 years to take into account disease latency. RESULTS: There was an overall excess of lung cancer (SMR 1.41; 52 observed). The SMRs for four categories of increasing crystalline silica among the workers not exposed to asbestos were 1.13, 0.87, 2.14, 2.00. An SMR of 8.31 (three observed) was found for workers with the highest cumulative exposure to both dusts. Internal analysis, after adjustment for asbestos exposure, yielded rate ratios for categories of exposure to crystalline silica: 1.00 (reference), 1.37, 1.80, and 1.79. CONCLUSIONS: Asbestos exposure was not an important confounder of the association between crystalline silica and mortality from lung cancer in this cohort. Although based on a small number of deaths from lung cancer, the data suggest possible synergy between these exposures. An extended follow up of this cohort is in progress and should enable better assessments of independent and combined effects on risk of lung cancer. PMID:8882123

Type A personality, hostility, time urgency and unintentional injuries among Chinese undergraduates: a matched case–control study

PubMed Central

2013-01-01

Background Associations between type A behaviour pattern (TABP) and injuries are inconsistent. These inconsistencies may be due to different effects of various components of TABP, namely time urgency/impatience, hostility and competitive drive. It is important to examine the relationship between the global TABP, its two components, and unintentional injuries, among undergraduates in China. Methods On the basis of a previous cross-sectional study, we conducted a matched case–control study. 253 cases and an equal number of age-, gender-, and major-matched controls were included. The questionnaire solicited socio-demographic information, the experience of injuries, the scale of TABP, and other potential confounding factors. Besides the correlation between the global TABP and injuries, the influences of the two components of TABP on injuries were also evaluated. Conditional logistic regression was used to determine the crude odds ratios (ORs) and adjusted ORs of injury events. Results A dose–response relationship was apparent among students who rated themselves higher on the TABP scale (P-value for trend, 0.002), with a crude OR of 2.93 (95% CI: 0.93–9.19) for injuries comparing those with TABP to those with type B behaviour pattern (TBBP). After adjustment for potential confounding factors, TABP remained statistically significant, and the adjusted OR was 5.52 (95% CI: 1.43–21.27); from a comparison of students with TABP to those with TBBP. A dose–response relationship was also apparent between the hostility component and nonfatal injuries, both in crude analysis and after adjusting for other confounders. The relationship between time-hurry and injuries was not statistically significant, based on univariate and multivariate analyses. Conclusions Both the global TABP and the hostility component were associated with a dose response increase in the risk of non-fatal unintentional injuries among Chinese undergraduates. Further studies need to be conducted to confirm or reject this correlation. PMID:24219492

Application of an In Vivo Hepatic Triacylglycerol Production Method in the Setting of a High-Fat Diet in Mice

PubMed Central

Ono-Moore, Kikumi D.; Ferguson, Matthew; Blackburn, Michael L.; Issafras, Hassan; Adams, Sean H.

2016-01-01

High-fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Dysfunction of triacylglycerol (TAG) metabolism may contribute to the development of hepatic steatosis, via increased de novo lipogenesis or repackaging of circulating nonesterified fatty acids (NEFAs). Hepatic TAG production (HTP) rate can be assessed through injecting mice with nonionic detergents that inhibit tissue lipoprotein lipase. Potential confounding effects of detergent-based HTP tests (HTPTs) used in longitudinal studies—including the impact on food intake, energy balance, and weight gain—have not been reported. To examine this, male C57BL/6J mice were fed a 10% or 60% kcal diet. After 4 weeks, the mice underwent an HTPT via poloxamer 407 intraperitoneal injections (1000 mg/kg). Weight gain, energy intake, and postabsorptive TAG levels normalized 7–10 days post-HTPT. The post-HTPT recovery of body weight and energy intake suggest that, in metabolic phenotyping studies, any additional sample collection should occur at least 7–10 days after the HTPT to reduce confounding effects. Diet-specific effects on HTP were also observed: HF-fed mice had reduced HTP, plasma TAG, and NEFA levels compared to controls. In conclusion, the current study highlights the procedural and physiological complexities associated with studying lipid metabolism using a HTPT in the DIO mouse model. PMID:28036028

Low socioeconomic status is a risk factor for preeclampsia: the Generation R Study.

PubMed

Silva, Lindsay M; Coolman, Marianne; Steegers, Eric Ap; Jaddoe, Vincent Wv; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

2008-06-01

To examine whether maternal socioeconomic status, as indicated by maternal educational level, is associated with preeclampsia, and if so, to what extent known risk factors for preeclampsia mediate the effect of educational level. In the Generation R Study, a population-based cohort study, we examined data of 3547 pregnant women. Odds ratios of preeclampsia for low, mid-low and mid-high educational level compared with high educational level were calculated after adjustment for confounders and additional adjustment for a selection of potential mediators (family history, material factors, psychosocial factors, substance use, working conditions, preexisting medical conditions, maternal anthropometrics and blood pressure at enrollment) that individually caused more than 10% change in the odds ratio for low education. Adjusted for the confounding effects of age, gravidity and multiple pregnancy, women with low educational level were more likely to develop preeclampsia (odds ratio 5.12; 95% confidence interval: 2.20, 11.93) than women with high educational level. After additional adjustment for financial difficulties, smoking in pregnancy, working conditions, body mass index and blood pressure at enrollment, the odds ratio was 4.91 (95% confidence interval: 1.93, 12.52). Low maternal socioeconomic status is a strong risk factor for preeclampsia. Only a small part of this association can be explained by the mediating effects of established risk factors for preeclampsia. Further research is needed to disentangle the pathway from low socioeconomic status to preeclampsia.

Application of an In Vivo Hepatic Triacylglycerol Production Method in the Setting of a High-Fat Diet in Mice.

PubMed

Ono-Moore, Kikumi D; Ferguson, Matthew; Blackburn, Michael L; Issafras, Hassan; Adams, Sean H

2016-12-28

High-fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Dysfunction of triacylglycerol (TAG) metabolism may contribute to the development of hepatic steatosis, via increased de novo lipogenesis or repackaging of circulating nonesterified fatty acids (NEFAs). Hepatic TAG production (HTP) rate can be assessed through injecting mice with nonionic detergents that inhibit tissue lipoprotein lipase. Potential confounding effects of detergent-based HTP tests (HTPTs) used in longitudinal studies-including the impact on food intake, energy balance, and weight gain-have not been reported. To examine this, male C57BL/6J mice were fed a 10% or 60% kcal diet. After 4 weeks, the mice underwent an HTPT via poloxamer 407 intraperitoneal injections (1000 mg/kg). Weight gain, energy intake, and postabsorptive TAG levels normalized 7-10 days post-HTPT. The post-HTPT recovery of body weight and energy intake suggest that, in metabolic phenotyping studies, any additional sample collection should occur at least 7-10 days after the HTPT to reduce confounding effects. Diet-specific effects on HTP were also observed: HF-fed mice had reduced HTP, plasma TAG, and NEFA levels compared to controls. In conclusion, the current study highlights the procedural and physiological complexities associated with studying lipid metabolism using a HTPT in the DIO mouse model.

Exposure to violence in childhood is associated with higher body mass index in adolescence.

PubMed

Gooding, Holly C; Milliren, Carly; Austin, S Bryn; Sheridan, Margaret A; McLaughlin, Katie A

2015-12-01

To determine whether different types of childhood adversity are associated with body mass index (BMI) in adolescence, we studied 147 adolescents aged 13-17 years, 41% of whom reported exposure to at least one adversity (maltreatment, abuse, peer victimization, or witness to community or domestic violence). We examined associations between adversity type and age- and sex-specific BMI z-scores using linear regression and overweight and obese status using logistic regression. We adjusted for potential socio-demographic, behavioral, and psychological confounders and tested for effect modification by gender. Adolescents with a history of sexual abuse, emotional abuse, or peer victimization did not have significantly different BMI z-scores than those without exposure (p>0.05 for all comparisons). BMI z-scores were higher in adolescents who had experienced physical abuse (β=0.50, 95% CI 0.12-0.91) or witnessed domestic violence (β=0.85, 95% CI 0.30-1.40). Participants who witnessed domestic violence had almost 6 times the odds of being overweight or obese (95% CI: 1.09-30.7), even after adjustment for potential confounders. No gender-by-adversity interactions were found. Exposure to violence in childhood is associated with higher adolescent BMI. This finding highlights the importance of screening for violence in pediatric practice and providing obesity prevention counseling for youth. Copyright © 2015 Elsevier Ltd. All rights reserved.

P300 Source Localization Contrasts in Body-Focused Repetitive Behaviors and Tic Disorders

PubMed Central

Sauvé, Geneviève; O’Connor, Kieron P.; Blanchet, Pierre J.

2017-01-01

Tic disorders (TD) and body-focused repetitive behaviors (BFRB) have similar phenotypes that can be challenging to distinguish in clinical settings. Both disorders show high rates of comorbid psychiatric conditions, dysfunctional basal ganglia activity, atypical cortical functioning in the prefrontal and motor cortical regions, and cognitive deficits. Clinicians frequently confound the two disorders and it is important to find reliable objective methods to discriminate TD and BFRB. Neuropsychological tests and event-related potential (ERP) studies have yielded inconsistent results regarding a possible context updating deficit in TD and BFRB patients. However, most previous studies did not control for the presence of comorbid psychiatric condition and medication status, which might have confounded the findings reported to date. Hence, we aimed to investigate the psychophysiology of working memory using ERP in carefully screened TD and BFRB patients excluding those with psychiatric comorbidity and those taking psychoactive medication. The current study compared 12 TD patients, 12 BRFB patients, and 15 healthy control participants using a motor oddball task (button press). The P300 component was analyzed as an index of working memory functioning. Results showed that BFRB patients had decreased P300 oddball effect amplitudes over the right hemisphere compared to the TD and control groups. Clinical groups presented different scalp distributions compared to controls, which could represent a potential endophenotype candidate of BFRB and TD. PMID:28671557

Impact sports and bone fractures among adolescents.

PubMed

Lynch, Kyle R; Kemper, Han C G; Turi-Lynch, Bruna; Agostinete, Ricardo R; Ito, Igor H; Luiz-De-Marco, Rafael; Rodrigues-Junior, Mario A; Fernandes, Rômulo A

2017-12-01

The objective of the present study was to investigate the effects of different sports on stress fractures among adolescents during a 9-month follow-up period. The sample was composed of 184 adolescents divided into three groups (impact sports [n = 102]; swimming [n = 35]; non-sports [n = 47]). The occurrence of stress fracture was reported by participants and coaches. As potential confounders we considered age, sex, resistance training, body composition variables and age at peak of height velocity. There were 13 adolescents who reported fractures during the 9-month period. Bone mineral density values were higher in adolescents engaged in impact sports (P-value = 0.002). Independently of confounders, the risk of stress fracture was lower in adolescents engaged in impact sports than in non-active adolescents (hazard ratio [HR] = 0.23 [95% confidence interval (CI) = 0.05 to 0.98]), while swimming practice was not associated to lower risk of fracture (HR = 0.49 [95% CI = 0.09 to 2.55]). In conclusion, the findings from this study indicate the importance of sports participation among adolescents in the reduction of stress fracture risk, especially with impact sports. More importantly, these results could be relevant for recognising adolescents in danger of not reaching their potential for peak bone mass and later an increased risk of fractures.

A blunted diurnal cortisol response in the lower educated does not explain educational differences in coronary heart disease: findings from the AGES-Reykjavik study.

PubMed

Groffen, Daniëlle A I; Bosma, Hans; Koster, Annemarie; von Bonsdorff, Mikaela B; Aspelund, Thor; Eiriksdottir, Gudny; Penninx, Brenda W J H; Kempen, Gertrudis I J M; Kirschbaum, Clemens; Gudnason, Vilmundur; Harris, Tamara B

2015-02-01

Lower educational attainment generally is a strong predictor of coronary heart disease (CHD). The underlying mechanisms of this effect are, however, less clear. One hypothesis is that stress related to limitations imposed by lower socioeconomic status elicits changes in hypothalamic-pituitary-adrenal axis functioning, which, in turn, increases risk of CHD. In a large cohort study, we examined whether educational attainment was related to risk of fatal and non-fatal CHD and the extent to which salivary cortisol mediated this relation independent of potential confounders, including lifestyles. Data came from 3723 participants aged 66 through 96 from the Age, Gene/Environment Susceptibility (AGES) - Reykjavik Study. Between 2002 and 2006, data were collected using questionnaires and examinations including morning and evening salivary samples. Hospital admission records and cause of death registries (ICD-9 and ICD-10 codes) were available until December 2009. Linear regression and Cox proportional hazards analyses were performed. Even after adjustment for potential confounders, including lifestyle, persons with lower educational attainment showed a blunted cortisol response and also greater risk of incident CHD. However, our data did not support the role of cortisol as a mediator in the association between education and CHD in an older sample (192). Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of medical malpractice liability on rate of referrals received by specialist physicians.

PubMed

Xu, Xiao; Spurr, Stephen J; Nan, Bin; Fendrick, A Mark

2013-10-01

Using nationally representative data from the United States, this paper analyzed the effect of a state’s medical malpractice environment on referral visits received by specialist physicians. The analytic sample included 12,839 ambulatory visits to specialist care doctors in office-based settings in the United States during 2003–2007. Whether the patient was referred for the visit was examined for its association with the state’s malpractice environment, assessed by the frequency and severity of paid medical malpractice claims, medical malpractice insurance premiums and an indicator for whether the state had a cap on non-economic damages. After accounting for potential confounders such as economic or professional incentives within practices, the analysis showed that statutory caps on non-economic damages of $250,000 were significantly associated with lower likelihood of a specialist receiving referrals, suggesting a potential impact of a state’s medical malpractice environment on physicians’ referral behavior.

The Effect of Medical Malpractice Liability on Rate of Referrals Received by Specialist Physicians

PubMed Central

Xu, Xiao; Spurr, Stephen J.; Nan, Bin; Fendrick, A. Mark

2013-01-01

Using nationally representative data from the U.S., this paper analyzed the effect of a state’s medical malpractice environment on referral visits received by specialist physicians. The analytic sample included 12,839 ambulatory visits to specialist care doctors in office-based settings in the U.S. during 2003–2007. Whether the patient was referred for the visit was examined for its association with the state’s malpractice environment, assessed by the frequency and severity of paid medical malpractice claims, medical malpractice insurance premiums, and an indicator for whether the state had a cap on noneconomic damages. After accounting for potential confounders such as economic or professional incentives within practices, the analysis showed that statutory caps on noneconomic damages of $250,000 were significantly associated with lower likelihood of a specialist receiving referrals, suggesting a potential impact of a state’s medical malpractice environment on physicians’ referral behavior. PMID:23527533

Case mix adjusted nursing-home reimbursement: a critical review of the evidence.

PubMed

Weissert, W G; Musliner, M C

1992-01-01

Nursing-home case mix adjusted payment systems typically base payments on estimates of patients' care needs, but to date the data on their effectiveness are ambiguous. Studies mainly show that access for patients most in need of care appears to improve under these systems. Case mix based payment systems have both positive and negative effects on quality of care and require compensating mechanisms for the potentially harmful incentives they can generate. On the positive side, nursing homes are paid more equitably; the negative aspect is reflected in higher costs, particularly for administration. A Health Care Financing Administration (HCFA) demonstration project may provide insights, but its limited number of predominantly small, rural, participating states, its tandem quality assurance system, and potentially confounding market variables may restrict the value of this project. We do not yet have the data to assess the impact of instituting case mix adjustment systems.

Accounting for context in studies of health inequalities: a review and comparison of analytic approaches.

PubMed

Schempf, Ashley H; Kaufman, Jay S

2012-10-01

A common epidemiologic objective is to evaluate the contribution of residential context to individual-level disparities by race or socioeconomic position. We reviewed analytic strategies to account for the total (observed and unobserved factors) contribution of environmental context to health inequalities, including conventional fixed effects (FE) and hybrid FE implemented within a random effects (RE) or a marginal model. To illustrate results and limitations of the various analytic approaches of accounting for the total contextual component of health disparities, we used data on births nested within neighborhoods as an applied example of evaluating neighborhood confounding of racial disparities in gestational age at birth, including both a continuous and a binary outcome. Ordinary and RE models provided disparity estimates that can be substantially biased in the presence of neighborhood confounding. Both FE and hybrid FE models can account for cluster level confounding and provide disparity estimates unconfounded by neighborhood, with the latter having greater flexibility in allowing estimation of neighborhood-level effects and intercept/slope variability when implemented in a RE specification. Given the range of models that can be implemented in a hybrid approach and the frequent goal of accounting for contextual confounding, this approach should be used more often. Published by Elsevier Inc.

Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

PubMed

Landau, Sabine; Emsley, Richard; Dunn, Graham

2018-06-01

Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of the three processes involving baseline measures of intermediate or clinical outcomes is operating. Necessary assumptions for the change score approach (B) to provide unbiased estimates under either process include the independence of baseline measures and change scores of the intermediate variable. Finally, estimates provided by the analysis of covariance approach (C) were found to be unbiased under all the three processes considered here. When applied to the example, there was evidence of mediation under all methods but the estimate of the indirect effect depended on the approach used with the proportion mediated varying from 57% to 86%. Trialists planning mediation analyses should measure baseline values of putative mediators as well as of continuous clinical outcomes. An analysis of covariance approach is recommended to avoid potential biases due to confounding processes involving baseline measures of intermediate or clinical outcomes, and not simply for increased precision.

Distinct cognitive control mechanisms as revealed by modality-specific conflict adaptation effects.

PubMed

Yang, Guochun; Nan, Weizhi; Zheng, Ya; Wu, Haiyan; Li, Qi; Liu, Xun

2017-04-01

Cognitive control is essential to resolve conflict in stimulus-response compatibility (SRC) tasks. The SRC effect in the current trial is reduced after an incongruent trial as compared with a congruent trial, a phenomenon being termed conflict adaptation (CA). The CA effect is found to be domain-specific , such that it occurs when adjacent trials contain the same type of conflict, but disappears when the conflicts are of different types. Similar patterns have been observed when tasks involve different modalities, but the modality-specific effect may have been confounded by task switching. In the current study, we investigated whether or not cognitive control could transfer across auditory and visual conflicts when task-switching was controlled. Participants were asked to respond to a visual or auditory (Experiments 1A/B) stimulus, with conflict coming from either the same or a different modality. CA effects showed modality-specific patterns. To account for potential confounding effects caused by differences in task-irrelevant properties, we specifically examined the influence of task-irrelevant properties on CA effects within the visual modality (Experiments 2A/B). Significant CA effects were observed across different conflicts from distinct task-irrelevant properties, ruling out that the lack of cross-modal CA effects in Experiments 1A/B resulted from differences in task-irrelevant information. Task-irrelevant properties were further matched in Experiments 3A/B to examine the pure effect of modality. Results replicated Experiments 1A/B showing robust modality-specific CA effects. Taken together, we provide supporting evidences that modality affects cognitive control in conflict resolution, which should be taken into account in theories of cognitive control. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Correlates of residential wiring code used in studies of health effects of residential electromagnetic fields.

PubMed

Bracken, M B; Belanger, K; Hellenbrand, K; Addesso, K; Patel, S; Triche, E; Leaderer, B P

1998-09-01

The home wiring code is the most widely used metric for studies of residential electromagnetic field (EMF) exposure and health effects. Despite the fact that wiring code often shows stronger correlations with disease outcome than more direct EMF home assessments, little is known about potential confounders of the wiring code association. In a study carried out in southern Connecticut in 1988-1991, the authors used strict and widely used criteria to assess the wiring codes of 3,259 homes in which respondents lived. They also collected other home characteristics from the tax assessor's office, estimated traffic density around the home from state data, and interviewed each subject (2,967 mothers of reproductive age) for personal characteristics. Women who lived in very high current configuration wiring coded homes were more likely to be in manual jobs and their homes were older (built before 1949, odds ratio (OR) = 73.24, 95% confidence interval (CI) 29.53-181.65) and had lower assessed value and higher traffic densities (highest density quartile, OR = 3.99, 95% CI 1.17-13.62). Because some of these variables have themselves been associated with health outcomes, the possibility of confounding of the wiring code associations must be rigorously evaluated in future EMF research.

Evaluation of Practice Effect on Neuropsychological Measures among Persons With and Without HIV Infection in Northern India

PubMed Central

Ownby, Raymond L.; Waldrop-Valverde, Drenna; Jones, Deborah L.; Sharma, Sunil; Nehra, Ritu; Kumar, Adarsh M.; Prabhakar, Sudesh; Acevedo, Amarilis; Kumar, Mahendra

2016-01-01

An evaluation of the effects of HIV infection on neurocognition over time is important for understanding disease progression. Changes in cognitive function can be evaluated longitudinally using neuropsychological testing at repeated intervals. The assessment of change over time, however, is complicated by the potentially confounding influence of learning on repeated test administrations, often referred to as practice effect. In this study, we present data on testing of persons with or without HIV infection on a battery administered at study baseline and repeated one year later. Results suggest that practice effects may be diminished in persons with HIV infection compared to without it. This appears to be true even among those with relatively intact immune functioning as measured by CD4 count. PMID:27739034

Assessing the independent contribution of maternal educational expectations to children's educational attainment in early adulthood: a propensity score matching analysis.

PubMed

Pingault, Jean Baptiste; Côté, Sylvana M; Petitclerc, Amélie; Vitaro, Frank; Tremblay, Richard E

2015-01-01

Parental educational expectations have been associated with children's educational attainment in a number of long-term longitudinal studies, but whether this relationship is causal has long been debated. The aims of this prospective study were twofold: 1) test whether low maternal educational expectations contributed to failure to graduate from high school; and 2) compare the results obtained using different strategies for accounting for confounding variables (i.e. multivariate regression and propensity score matching). The study sample included 1,279 participants from the Quebec Longitudinal Study of Kindergarten Children. Maternal educational expectations were assessed when the participants were aged 12 years. High school graduation—measuring educational attainment—was determined through the Quebec Ministry of Education when the participants were aged 22-23 years. Findings show that when using the most common statistical approach (i.e. multivariate regressions to adjust for a restricted set of potential confounders) the contribution of low maternal educational expectations to failure to graduate from high school was statistically significant. However, when using propensity score matching, the contribution of maternal expectations was reduced and remained statistically significant only for males. The results of this study are consistent with the possibility that the contribution of parental expectations to educational attainment is overestimated in the available literature. This may be explained by the use of a restricted range of potential confounding variables as well as the dearth of studies using appropriate statistical techniques and study designs in order to minimize confounding. Each of these techniques and designs, including propensity score matching, has its strengths and limitations: A more comprehensive understanding of the causal role of parental expectations will stem from a convergence of findings from studies using different techniques and designs.

A case study of nurse practitioner care compared to general practitioner care for children with respiratory tract infections.

PubMed

van Vugt, Saskia F; van de Pol, Alma C; Cleveringa, Frits G W; Stellato, Rebecca K; Kappers, Marieke P; de Wit, Niek J; Damoiseaux, Roger A M J

2018-05-13

To compare quality of care provided by nurse practitioners with care provided by general practitioners for children with respiratory tract infections in the Netherlands. Nurse practitioners increasingly manage acute conditions in general practice, with opportunities for more protocolled care. Studies on quality of nurse practitioners' care for children with respiratory tract infections are limited to the US health care system and do not take into account baseline differences in illness severity. Retrospective observational cohort study. Data were extracted from electronic healthcare records of children 0-6 years presenting with respiratory tract infection between January-December 2013. Primary outcomes were antibiotic prescriptions and early return visits. Generalized estimating equations were used to correct for potential confounders. A total of 899 respiratory tract infection consultations were assessed (168 seen by nurse practitioner; 731 by general practitioners). Baseline characteristics differed between these groups. Overall antibiotic prescription and early return visit rates were 21% and 24%, respectively. Adjusted odds ratio for antibiotic prescription after nurse practitioner vs. general practitioner delivered care was 1.40 (95% confidence interval 0.89-2.22) and for early return visits 1.53 (95% confidence interval 1.01-2.31). Important confounder for antibiotic prescription was illness severity. Presence of wheezing was a confounder for return visits. Complication and referral rates did not differ. Antibiotic prescription, complication and referral rates for paediatric respiratory tract infection consultations did not differ significantly between nurse practitioner and general practitioner consultations, after correction for potential confounders. General practitioners, however, see more severely ill children and have a lower return visit rate. A randomised controlled study is needed to determine whether nurse practitioner care quality is truly non-inferior. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tutorial in Biostatistics: Instrumental Variable Methods for Causal Inference*

PubMed Central

Baiocchi, Michael; Cheng, Jing; Small, Dylan S.

2014-01-01

A goal of many health studies is to determine the causal effect of a treatment or intervention on health outcomes. Often, it is not ethically or practically possible to conduct a perfectly randomized experiment and instead an observational study must be used. A major challenge to the validity of observational studies is the possibility of unmeasured confounding (i.e., unmeasured ways in which the treatment and control groups differ before treatment administration which also affect the outcome). Instrumental variables analysis is a method for controlling for unmeasured confounding. This type of analysis requires the measurement of a valid instrumental variable, which is a variable that (i) is independent of the unmeasured confounding; (ii) affects the treatment; and (iii) affects the outcome only indirectly through its effect on the treatment. This tutorial discusses the types of causal effects that can be estimated by instrumental variables analysis; the assumptions needed for instrumental variables analysis to provide valid estimates of causal effects and sensitivity analysis for those assumptions; methods of estimation of causal effects using instrumental variables; and sources of instrumental variables in health studies. PMID:24599889

Paternal age at childbirth and eating disorders in offspring.

PubMed

Javaras, K N; Rickert, M E; Thornton, L M; Peat, C M; Baker, J H; Birgegård, A; Norring, C; Landén, M; Almqvist, C; Larsson, H; Lichtenstein, P; Bulik, C M; D'Onofrio, B M

2017-02-01

Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence. Data for 2 276 809 individuals born in Sweden 1979-2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987-2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history. Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25-29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14-1.53] for AN and 1.26 (95% CI 1.13-1.40) for AED. In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.

Food insecurity and malnutrition in Chinese elementary school students.

PubMed

Shen, Xiuhua; Gao, Xiang; Tang, Wenjing; Mao, Xuanxia; Huang, Jingyan; Cai, Wei

2015-09-28

It has been shown that food insecurity is associated with poor diet quality and unfavourable health outcomes. However, little is known about the potential effects of food insecurity on the overall malnutrition status among children. In this study, we investigated the prevalence of food insecurity among 1583 elementary school students, aged 6-14 years, living in Chinese rural areas and examined its association with four malnutrition signs, including rickets sequelae, anaemia, stunting and wasting. Information on food security was collected via questionnaires. Rickets sequelae were assessed by an experienced paediatrician during the interview. Anaemia was determined by the WHO Hb thresholds adjusted by the local altitude. Weight and height were measured during the interview. Stunting and wasting were then evaluated according to WHO child growth standards (2007). We examined the association between food insecurity and the number of malnutrition signs (total number = 4), and the likelihood of having severe malnutrition (presence of 3+ signs), after adjusting for potential confounders, such as age, social-economic status and dietary intakes. During the previous 12 months, the overall prevalence of food insecurity was 6.1% in the entire studied population and 16.3% in participants with severe malnutrition. Participants with food insecurity had a slightly higher number of malnutrition signs (1.14 v. 0.96; P=0.043) relative to those who were food secure, after adjusting for potential confounders. Food insecurity was also associated with increased likelihood of having severe malnutrition (adjusted OR 3.08; 95% CI 1.47, 6.46; P=0.003). In conclusion, food insecurity is significantly associated with malnutrition among Chinese children in this community.

Epidemiologic studies of electric and magnetic fields and cancer: strategies for extending knowledge.

PubMed Central

Savitz, D A

1993-01-01

Epidemiologic research concerning electric and magnetic fields in relation to cancer has focused on the potential etiologic roles of residential exposure on childhood cancer and occupational exposure on adult leukemia and brain cancer. Future residential studies must concentrate on exposure assessment that is enhanced by developing models of historical exposure, assessment of the relation between magnetic fields and wire codes, and consideration of alternate exposure indices. Study design issues deserving attention include possible biases in random digit dialing control selection, consideration of the temporal course of exposure and disease, and acquisition of the necessary information to assess the potential value of ecologic studies. Highest priorities are comprehensive evaluation of exposure patterns and sources and examination of the sociology and geography of residential wire codes. Future occupational studies should also concentrate on improved exposure assessment with increased attention to nonutility worker populations and development of historical exposure indicators that are superior to job titles alone. Potential carcinogens in the workplace that could act as confounders need to be more carefully examined. The temporal relation between exposure and disease and possible effect modification by other workplace agents should be incorporated into future studies. The most pressing need is for measurement of exposure patterns in a variety of worker populations and performance of traditional epidemiologic evaluations of cancer occurrence. The principal source of bias toward the null is nondifferential misclassification of exposure with improvements expected to enhance any true etiologic association that is present. Biases away from the null might include biased control selection in residential studies and chemical carcinogens acting as confounders in occupational studies. PMID:8206046

Weight Loss and Coronary Heart Disease: Sensitivity Analysis for Unmeasured Confounding by Undiagnosed Disease.

PubMed

Danaei, Goodarz; Robins, James M; Young, Jessica G; Hu, Frank B; Manson, JoAnn E; Hernán, Miguel A

2016-03-01

Evidence for the effect of weight loss on coronary heart disease (CHD) or mortality has been mixed. The effect estimates can be confounded due to undiagnosed diseases that may affect weight loss. We used data from the Nurses' Health Study to estimate the 26-year risk of CHD under several hypothetical weight loss strategies. We applied the parametric g-formula and implemented a novel sensitivity analysis for unmeasured confounding due to undiagnosed disease by imposing a lag time for the effect of weight loss on chronic disease. Several sensitivity analyses were conducted. The estimated 26-year risk of CHD did not change under weight loss strategies using lag times from 0 to 18 years. For a 6-year lag time, the risk ratios of CHD for weight loss compared with no weight loss ranged from 1.00 (0.99, 1.02) to 1.02 (0.99, 1.05) for different degrees of weight loss with and without restricting the weight loss strategy to participants with no major chronic disease. Similarly, no protective effect of weight loss was estimated for mortality risk. In contrast, we estimated a protective effect of weight loss on risk of type 2 diabetes. We estimated that maintaining or losing weight after becoming overweight or obese does not reduce the risk of CHD or death in this cohort of middle-age US women. Unmeasured confounding, measurement error, and model misspecification are possible explanations but these did not prevent us from estimating a beneficial effect of weight loss on diabetes.

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

PubMed Central

2010-01-01

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action. PMID:21143861

Cost-effectiveness of using small vertebrates as indicators of disturbance.

PubMed

Peck, Mika Robert; Maddock, Simon T; Morales, Jorge Noe; Oñate, Hugolino; Mafla-Endara, Paola; Peñafiel, Vanessa Aguirre; Torres-Carvajal, Omar; Pozo-Rivera, Wilmer E; Cueva-Arroyo, Xavier A; Tolhurst, Bryony A

2014-10-01

In species-rich tropical forests, effective biodiversity management demands measures of progress, yet budgetary limitations typically constrain capacity of decision makers to assess response of biological communities to habitat change. One approach is to identify ecological-disturbance indicator species (EDIS) whose monitoring is also monetarily cost-effective. These species can be identified by determining individual species' responses to disturbance across a gradient; however, such responses may be confounded by factors other than disturbance. For example, in mountain environments the effects of anthropogenic habitat alteration are commonly confounded by elevation. EDIS have been identified with the indicator value (IndVal) metric, but there are weaknesses in the application of this approach in complex montane systems. We surveyed birds, small mammals, bats, and leaf-litter lizards in differentially disturbed cloud forest of the Ecuadorian Andes. We then incorporated elevation in generalized linear (mixed) models (GL(M)M) to screen for EDIS in the data set. Finally, we used rarefaction of species accumulation data to compare relative monetary costs of identifying and monitoring EDIS at equal sampling effort, based on species richness. Our GL(M)M generated greater numbers of EDIS but fewer characteristic species relative to IndVal. In absolute terms birds were the most cost-effective of the 4 taxa surveyed. We found one low-cost bird EDIS. In terms of the number of indicators generated as a proportion of species richness, EDIS of small mammals were the most cost-effective. Our approach has the potential to be a useful tool for facilitating more sustainable management of Andean forest systems. © 2014 Society for Conservation Biology.

Quasi-experimental study designs series-paper 9: collecting data from quasi-experimental studies.

PubMed

Aloe, Ariel M; Becker, Betsy Jane; Duvendack, Maren; Valentine, Jeffrey C; Shemilt, Ian; Waddington, Hugh

2017-09-01

To identify variables that must be coded when synthesizing primary studies that use quasi-experimental designs. All quasi-experimental (QE) designs. When designing a systematic review of QE studies, potential sources of heterogeneity-both theory-based and methodological-must be identified. We outline key components of inclusion criteria for syntheses of quasi-experimental studies. We provide recommendations for coding content-relevant and methodological variables and outlined the distinction between bivariate effect sizes and partial (i.e., adjusted) effect sizes. Designs used and controls used are viewed as of greatest importance. Potential sources of bias and confounding are also addressed. Careful consideration must be given to inclusion criteria and the coding of theoretical and methodological variables during the design phase of a synthesis of quasi-experimental studies. The success of the meta-regression analysis relies on the data available to the meta-analyst. Omission of critical moderator variables (i.e., effect modifiers) will undermine the conclusions of a meta-analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

The time course of symbolic number adaptation: oscillatory EEG activity and event-related potential analysis.

PubMed

Hsu, Yi-Fang; Szűcs, Dénes

2012-02-15

Several functional magnetic resonance imaging (fMRI) studies have used neural adaptation paradigms to detect anatomical locations of brain activity related to number processing. However, currently not much is known about the temporal structure of number adaptation. In the present study, we used electroencephalography (EEG) to elucidate the time course of neural events in symbolic number adaptation. The numerical distance of deviants relative to standards was manipulated. In order to avoid perceptual confounds, all levels of deviants consisted of perceptually identical stimuli. Multiple successive numerical distance effects were detected in event-related potentials (ERPs). Analysis of oscillatory activity further showed at least two distinct stages of neural processes involved in the automatic analysis of numerical magnitude, with the earlier effect emerging at around 200ms and the later effect appearing at around 400ms. The findings support for the hypothesis that numerical magnitude processing involves a succession of cognitive events. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention.

PubMed

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M; Stuart, Elizabeth A

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration.

Not only body weight perception but also body mass index is relevant to suicidal ideation and self-harming behavior in Japanese adolescents.

PubMed

Kinoshita, Kuni; Kinoshita, Yoshihiro; Shimodera, Shinji; Nishida, Atsushi; Inoue, Ken; Watanabe, Norio; Oshima, Norihito; Akechi, Tatsuo; Sasaki, Tsukasa; Inoue, Shimpei; Furukawa, Toshiaki A; Okazaki, Yuji

2012-04-01

Whether a low body mass index (BMI) is directly associated with a high risk of suicidal ideation or self-harming behavior in adolescents is still inconclusive. This study has, therefore, evaluated the relevance of BMI to suicidal ideation and self-harming behavior after controlling for body weight perception (BWP) and other potential confounding factors. BMI, BWP, suicidal ideation, and self-harming behavior were all assessed using a self-report questionnaire administered to 18,104 Japanese adolescents. Potential confounding factors were also evaluated. The data were then analyzed using bivariate and multivariate logistic regression. Low BMI was associated with suicidal ideation and deliberate self-harm when controlling for sex, age, drug use, emotional distress, and BWP. Low BMI may be an independent risk factor for suicidal ideation and deliberate self-harming behavior in Japanese adolescents.

Maternal obesity and childhood wheezing and asthma.

PubMed

Rusconi, Franca; Popovic, Maja

2017-03-01

Obesity represents one of the major public health problems worldwide, with an increased prevalence also among women of reproductive age. Maternal pre-pregnancy overweight and obesity are important risk factors for a number of maternal and foetal/neonatal complications. The objective of this review is to provide an overview of the most recent evidence regarding the associations between pre-pregnancy overweight/obesity and wheezing and asthma in childhood. Potential mechanisms, mediators and confounding factors involved in these associations are also discussed. Despite the relatively large body of studies examining these associations and taking into account main confounders and potential mediators, the causal relationship between maternal obesity and wheezing and asthma in childhood is still uncertain. This uncertainty is not trivial, as any prevention strategy aimed at reducing the burden of these conditions would necessarily imply better understanding of the factors that are in the causal chain. Copyright © 2016. Published by Elsevier Ltd.

Parent-based diagnosis of ADHD is as accurate as a teacher-based diagnosis of ADHD.

PubMed

Bied, Adam; Biederman, Joseph; Faraone, Stephen

2017-04-01

To review the literature evaluating the psychometric properties of parent and teacher informants relative to a gold-standard ADHD diagnosis in pediatric populations. We included studies that included both a parent and teacher informant, a gold-standard diagnosis, and diagnostic accuracy metrics. Potential confounds were evaluated. We also assessed the 'OR' and the 'AND' rules for combining informant reports. Eight articles met inclusion criteria. The diagnostic accuracy for predicting gold standard ADHD diagnoses did not differ between parents and teachers. Sample size, sample type, participant drop-out, participant age, participant gender, geographic area of the study, and date of study publication were assessed as potential confounds. Parent and teachers both yielded moderate to good diagnostic accuracy for ADHD diagnoses. Parent reports were statistically indistinguishable from those of teachers. The predictive features of the 'OR' and 'AND' rules are useful in evaluating approaches to better integrating information from these informants.

Non-nutritive sweeteners: evidence for benefit vs. risk.

PubMed

Gardner, Christopher

2014-02-01

Intake of added sugars in the American diet is high and has been linked to weight gain and adverse effects on glycemic control and diabetes. Several national health organizations recommend decreasing added sugars intake. Among the many strategies to consider to achieve this reduction is substitution with non-nutritive sweeteners (NNS - artificial sweeteners and stevia). The purpose of this review is to critically examine existing evidence for this strategy. Short-term intervention studies suggest that NNS, when substituted for added sugars, may be useful in supporting energy intake reduction, and promoting glycemic control and weight management. However, the magnitude of effect in these studies has ranged from modest to null. Compensatory eating behaviors likely diminish, and in some cases negate, potential effects. Findings from longer-term observational studies that examine associations between NNS use and obesity or type 2 diabetes are potentially confounded by reverse causality. Existing data are insufficient to clearly support or refute the effectiveness of substitution with NNS as a means of reducing added sugar intake. It is important to not lose sight of the impact of incorporating NNS-containing beverages and foods on overall diet quality when assessing potential health benefits vs. risks.

The contribution of fetal drug exposure to temperament: potential teratogenic effects on neuropsychiatric risk.

PubMed

Weiss, Sandra J; St Jonn-Seed, Mary; Harris-Muchell, Carolyn

2007-08-01

Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. High risk children (n = 120) were followed from birth to 6 months of age to determine the effects of fetal drug exposure on temperament, after controlling for the child's gender, gestational age, medical morbidity, ethnicity, and maltreatment as well as the mother's stress, income adequacy, and quality of caregiving. Methods included medical chart review, questionnaires, and videotapes of mother-child interaction. Preliminary analyses indicated that fetal drug exposure was associated with both distractibility and intensity of children's responses to the environment at 6 months of age. After adjusting for potentially confounding variables, drug exposure accounted for 12% of the variance in distractibility but was not a significant predictor in the regression model for intensity. Findings suggest that drug-exposed children may experience difficulty sustaining their focus of attention and be more easily distracted by environmental stimuli than non-drug-exposed children. Results converge with previous research to implicate cortical hyperarousal, stemming from teratogenic effects on the dopaminergic system during fetal development.

The spacing effect and metacognitive control.

PubMed

Mulligan, Neil W; Peterson, Daniel J

2014-01-01

Research suggests that spaced learning, compared with massed learning, results in superior long-term retention (the spacing effect). Son (2010) identified a potentially important moderator of the spacing effect: metacognitive control. Specifically, when participants chose massed restudy but were instead forced to space the restudy, the spacing effect disappeared in adults (or was reduced in children). This suggests spacing is less effective (or possibly ineffective) if implemented against the wishes of the learner. A closer examination of this paradigm, however, reveals that item-selection issues might alternatively explain the disappearance of the spacing effect. In the current experiments, we replicated the original design demonstrating that an item-selection confound is operating. Furthermore, relative to a more appropriate baseline, the spacing effect was significant and of the same size whether participants' restudy choices were honored or violated. In this paradigm, metacognitive control does not appear to moderate the spacing effect.

Associations of Cannabis and Cigarette Use with Depression and Anxiety at Age 18: Findings from the Avon Longitudinal Study of Parents and Children

PubMed Central

Gage, Suzanne H.; Hickman, Matthew; Heron, Jon; Munafò, Marcus R.; Lewis, Glyn; Macleod, John; Zammit, Stanley

2015-01-01

Introduction Substance use is associated with common mental health disorders, but the causal effect of specific substances is uncertain. We investigate whether adolescent cannabis and cigarette use is associated with incident depression and anxiety, while attempting to account for confounding and reverse causation. Methods We used data from ALSPAC, a UK birth cohort study, to investigate associations between cannabis or cigarettes (measured at age 16) and depression or anxiety (measured at age 18), before and after adjustment for pre-birth, childhood and adolescent confounders. Our imputed sample size was 4561 participants. Results Both cannabis (unadjusted OR 1.50, 95% CI 1.26, 1.80) and cigarette use (OR 1.37, 95% CI 1.16, 1.61) increased the odds of developing depression. Adjustment for pre-birth and childhood confounders partly attenuated these relationships though strong evidence of association persisted for cannabis use. There was weak evidence of association for cannabis (fully adjusted OR 1.30, 95% CI 0.98, 1.72) and insufficient evidence for association for cigarette use (fully adjusted OR = 0.97, 95% CI 0.75, 1.24) after mutually adjusting for each other, or for alcohol or other substance use. Neither cannabis nor cigarette use were associated with anxiety after adjustment for pre-birth and childhood confounders. Conclusions Whilst evidence of association between cannabis use and depression persisted after adjusting for pre-term and childhood confounders, our results highlight the difficulties in trying to estimate and interpret independent effects of cannabis and tobacco on psychopathology. Complementary methods are required to robustly examine effects of cannabis and tobacco on psychopathology. PMID:25875443

Estimating the monetary value of willingness to pay for E-book reader's attributes using partially confounded factorial conjoint choice experiment

NASA Astrophysics Data System (ADS)

Yong, Chin-Khian

2013-09-01

A partially confounded factorial conjoint choice experiments design was used to examine the monetary value of the willingness to pay for E-book Reader's attributes. Conjoint analysis is an efficient, cost-effective, and most widely used quantitative method in marketing research to understand consumer preferences and value trade-off. Value can be interpreted by customer or consumer as the received of multiple benefits from a price that was paid. The monetary value of willingness to pay for battery life, internal memory, external memory, screen size, text to Speech, touch screen, and converting handwriting to digital text of E-book reader were estimated in this study. Due to the significant interaction effect of the attributes with the price, the monetary values for the seven attributes were found to be different at different values of odds of purchasing versus not purchasing. The significant interactions effects were one of the main contribution of the partially confounded factorial conjoint choice experiment.

Resting-state FMRI confounds and cleanup

PubMed Central

Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

2013-01-01

The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

Metabolic syndrome and shift work: a systematic review.

PubMed

Canuto, Raquel; Garcez, Anderson S; Olinto, Maria T A

2013-12-01

The aim of this systematic review was to examine the association between shift work and metabolic syndrome (MetS) as well as the potential confounders investigated. A systematic search was conducted with the aim of finding original articles on the association between shift work and MetS. The included articles were chosen based on established inclusion criteria; their methodological quality was assessed using a validated quality checklist. A total of 10 articles were included in this review. The majority of the studies were classified as having a low risk of bias. The definitions of MetS and shift work varied between studies. Among the ten studies, eight found a positive association between shift work and MetS after controlling for socio-demographic and behavioral factors. Only three studies included sleep duration as a confounder, and these studies presented discordant results. We conclude that there was insufficient evidence regarding the association between shift work and prevalent MetS when the confounders are taken into account. Copyright © 2012 Elsevier Ltd. All rights reserved.

Can We Train Machine Learning Methods to Outperform the High-dimensional Propensity Score Algorithm?

PubMed

Karim, Mohammad Ehsanul; Pang, Menglan; Platt, Robert W

2018-03-01

The use of retrospective health care claims datasets is frequently criticized for the lack of complete information on potential confounders. Utilizing patient's health status-related information from claims datasets as surrogates or proxies for mismeasured and unobserved confounders, the high-dimensional propensity score algorithm enables us to reduce bias. Using a previously published cohort study of postmyocardial infarction statin use (1998-2012), we compare the performance of the algorithm with a number of popular machine learning approaches for confounder selection in high-dimensional covariate spaces: random forest, least absolute shrinkage and selection operator, and elastic net. Our results suggest that, when the data analysis is done with epidemiologic principles in mind, machine learning methods perform as well as the high-dimensional propensity score algorithm. Using a plasmode framework that mimicked the empirical data, we also showed that a hybrid of machine learning and high-dimensional propensity score algorithms generally perform slightly better than both in terms of mean squared error, when a bias-based analysis is used.

On negative outcome control of unobserved confounding as a generalization of difference-in-differences

PubMed Central

Sofer, Tamar; Richardson, David B.; Colicino, Elena; Schwartz, Joel; Tchetgen Tchetgen, Eric J.

2016-01-01

The difference-in-differences (DID) approach is a well known strategy for estimating the effect of an exposure in the presence of unobserved confounding. The approach is most commonly used when pre-and post-exposure outcome measurements are available, and one can assume that the association of the unobserved confounder with the outcome is equal in the two exposure groups, and constant over time. Then, one recovers the treatment effect by regressing the change in outcome over time on the exposure. In this paper, we interpret the difference-in-differences as a negative outcome control (NOC) approach. We show that the pre-exposure outcome is a negative control outcome, as it cannot be influenced by the subsequent exposure, and it is affected by both observed and unobserved confounders of the exposure-outcome association of interest. The relation between DID and NOC provides simple conditions under which negative control outcomes can be used to detect and correct for confounding bias. However, for general negative control outcomes, the DID-like assumption may be overly restrictive and rarely credible, because it requires that both the outcome of interest and the control outcome are measured on the same scale. Thus, we present a scale-invariant generalization of the DID that may be used in broader NOC contexts. The proposed approach is demonstrated in simulations and on a Normative Aging Study data set, in which Body Mass Index is used for NOC of the relationship between air pollution and inflammatory outcomes. PMID:28239233

The effect of alcohol advertising, marketing and portrayal on drinking behaviour in young people: systematic review of prospective cohort studies.

PubMed

Smith, Lesley A; Foxcroft, David R

2009-02-06

The effect of alcohol portrayals and advertising on the drinking behaviour of young people is a matter of much debate. We evaluated the relationship between exposure to alcohol advertising, marketing and portrayal on subsequent drinking behaviour in young people by systematic review of cohort (longitudinal) studies. studies were identified in October 2006 by searches of electronic databases, with no date restriction, supplemented with hand searches of reference lists of retrieved articles. Cohort studies that evaluated exposure to advertising or marketing or alcohol portrayals and drinking at baseline and assessed drinking behaviour at follow-up in young people were selected and reviewed. seven cohort studies that followed up more than 13,000 young people aged 10 to 26 years old were reviewed. The studies evaluated a range of different alcohol advertisement and marketing exposures including print and broadcast media. Two studies measured the hours of TV and music video viewing. All measured drinking behaviour using a variety of outcome measures. Two studies evaluated drinkers and non-drinkers separately. Baseline non-drinkers were significantly more likely to have become a drinker at follow-up with greater exposure to alcohol advertisements. There was little difference in drinking frequency at follow-up in baseline drinkers. In studies that included drinkers and non-drinkers, increased exposure at baseline led to significant increased risk of drinking at follow-up. The strength of the relationship varied between studies but effect sizes were generally modest. All studies controlled for age and gender, however potential confounding factors adjusted for in analyses varied from study to study. Important risk factors such as peer drinking and parental attitudes and behaviour were not adequately accounted for in some studies. data from prospective cohort studies suggest there is an association between exposure to alcohol advertising or promotional activity and subsequent alcohol consumption in young people. Inferences about the modest effect sizes found are limited by the potential influence of residual or unmeasured confounding.

Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data.

PubMed

Mantzorou, Maria; Pavlidou, Eleni; Vasios, George; Tsagalioti, Eftychia; Giaginis, Constantinos

2018-06-01

Numerous clinical trials have investigated the potential beneficial effects of curcumin supplementation against several human chronic diseases. Up to now, it has been claimed that curcumin consumption may exert beneficial effects against several chronic diseases by promoting human health and preventing diseases. In this aspect, the present review aims to critically collect and in-depth summarize the most recent, well-designed clinical studies evaluating the potential beneficial effects of curcumin consumption on human health promotion and disease prevention. According to recent and well-designed clinical studies, curcumin consumption may benefit against obesity, metabolic syndrome, and diabetes. Moreover, curcumin consumption seems to exert a positive effect on people suffering from various types of cancer, fatty liver disease, depression, arthritis, skin diseases, gut inflammation, and symptoms of premenstrual syndrome. Due to the strong heterogeneity among the clinical studies concerning the exact effective curcumin dose and formulation, as well as the recommended treatment duration for each chronic disease, no precise and definitive conclusions could be drawn. Further large-scale prospective studies are strongly recommended, being well-designed as far as follow-up times, dosage, formulation, and duration of curcumin supplementation are concerned. Moreover, potential confounders in each specific chronic disease should carefully be taken into account in future studies. Copyright © 2018 John Wiley & Sons, Ltd.

Confounder summary scores when comparing the effects of multiple drug exposures.

PubMed

Cadarette, Suzanne M; Gagne, Joshua J; Solomon, Daniel H; Katz, Jeffrey N; Stürmer, Til

2010-01-01

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.

Smoking and early retirement due to chronic disability.

PubMed

Bengtsson, Tommy; Nilsson, Anton

2018-05-01

This paper considers the long-term effects of smoking on disability retirement in Sweden. Smoking is known to have damaging effects on health, but there is limited evidence on how the effects of smoking translate into worse labour market outcomes, such as the inability to work. In contrast to the few previous studies on smoking and disability retirement, we use a large population sample with registry information on smoking, which is recorded for all women who give birth in Sweden. Thanks to these comprehensive data, we are able to account for a much broader range of potential confounders. In particular, by the use of sibling and twin fixed effects, we account for unobserved heterogeneity in childhood environment and family characteristics. Given that smoking is often initiated in adolescence, one would suspect such factors to play important roles. Among individuals aged 50-64 in 2011, a simple model suggested smokers to have a 5 percentage point higher probability of receiving (full) disability pension, making them more than twice as likely as non-smokers to receive this. However, in a model with sibling fixed effects, the size of the effect was reduced by more than a third. The results point to the importance of confounders, such as childhood circumstances or behaviours, which were not accounted for by previous studies. We also consider effects on disability due to different health conditions. In relative terms, effects are the largest for circulatory conditions and tumours. Results are largely driven by health problems severe enough to merit hospitalization, and there is no evidence of a role played by financial incentives. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlations between cannabis use and IQ change in the Dunedin cohort are consistent with confounding from socioeconomic status

PubMed Central

Rogeberg, Ole

2013-01-01

Does cannabis use have substantial and permanent effects on neuropsychological functioning? Renewed and intense attention to the issue has followed recent research on the Dunedin cohort, which found a positive association between, on the one hand, adolescent-onset cannabis use and dependence and, on the other hand, a decline in IQ from childhood to adulthood [Meier et al. (2012) Proc Natl Acad Sci USA 109(40):E2657–E2664]. The association is given a causal interpretation by the authors, but existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the Dunedin cohort, suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero. Further analyses of the Dunedin cohort are proposed to distinguish between the competing interpretations. Although it would be too strong to say that the results have been discredited, the methodology is flawed and the causal inference drawn from the results premature. PMID:23319626

Association between wrist ratio and carpal tunnel syndrome: Effect modification by body mass index.

PubMed

Thiese, Matthew S; Merryweather, Andrew; Koric, Alzina; Ott, Ulrike; Wood, Eric M; Kapellusch, Jay; Foster, James; Garg, Arun; Deckow-Schaefer, Gwen; Tomich, Suzanna; Kendall, Richard; Drury, David L; Wertsch, Jacqueline; Hegmann, Kurt T

2017-12-01

Previous studies have reported higher wrist ratios (WR) related to carpal tunnel syndrome (CTS) but have not assessed effect modification by obesity and may have inadequately controlled for confounders. Baseline data of a multicenter prospective cohort study were analyzed. CTS was defined by nerve conduction study (NCS) criteria and symptoms. Among the 1,206 participants, a square-shaped wrist was associated with CTS after controlling for confounders (prevalence ratio = 2.27; 95% confidence interval [95% CI], 1.33-3.86). Body mass index (BMI) was a strong effect modifier on the relationship between WR and both CTS and abnormal NCS results, with normal weight strata of rectangular versus square wrists = 8.18 (95% CI, 1.63-49.96) and 7.12 (95% CI, 2.19-23.16), respectively. A square wrist is significantly associated with CTS after controlling for confounders. Effect modification by high BMI masked the eightfold magnitude adjusted relationship seen between WR and CTS among normal weight participants. Muscle Nerve 56: 1047-1053, 2017. © 2017 Wiley Periodicals, Inc.

In vitro influence of light radiation on hair steroid concentrations.

PubMed

Grass, Juliane; Miller, Robert; Carlitz, Esther H D; Patrovsky, Fabian; Gao, Wei; Kirschbaum, Clemens; Stalder, Tobias

2016-11-01

Hair cortisol concentrations (hairF) are considered to be relatively robust to various confounding influences. However, a potentially important covariate factor that has received little attention in this context is hair exposure to ultraviolet/sunlight radiation. We conducted a detailed experimental investigation to examine the effects of light exposure on hair cortisol. In study I, a hydrocortisone-containing solution was subjected to short-term artificial light irradiation for 1, 3, 5, 10, 15, or 30min to evaluate the stability of cortisol molecules due to radiant energy. In study II, hair samples (N=12) were subjected to single short-term artificial light irradiation for 0, 1, or 5h to examine light-induced effects in the hair matrix. In study III, hair samples (N=25) were subjected to long-term naturalistic sunlight radiation over a period of two months (during summer) with daily exposure times of 0, 1, 3, or 6h, respectively. Besides cortisol, studies II & III also examined concentrations of cortisone (hairE), dehydroepiandrosterone (hairDHEA) and progesterone (hairP) in hair, quantified using LC-MS/MS technology. Results across the three studies consistently revealed effects of light irradiation on hair steroid concentrations: Longer light exposure resulted in a decrease of dissolved hydrocortisone (study I) as well as of hairF and hairE (studies II and III). Conversely, hairDHEA and hairP increased with longer natural sunlight exposure times (study III), while this effect was not observed for short-term artificial light irradiation (study II). Combined, our findings imply sunlight exposure as a potential confound in hair steroid research. Given the experimental character of this investigation, the magnitude of this effect under real-life testing conditions is difficult to estimate. To support future investigation into this, we designed a 'sunlight-exposure' questionnaire to share with the research community. The assessment and statistical accounting for sunlight exposure-related effects in future hair steroid research (using this or a similar questionnaire) may help to reduce the potential influence of this unwanted error source and could thus lead to more valid and reliable results. In addition, our data strongly suggest that hair samples for steroid analyses need to be stored in a dark environment. Copyright © 2016. Published by Elsevier Ltd.

Associations between Responsible Beverage Service Laws and Binge Drinking and Alcohol-Impaired Driving

PubMed Central

Linde, Ann C.; Toomey, Traci L.; Wolfson, Julian; Lenk, Kathleen M.; Jones-Webb, Rhonda; Erickson, Darin J.

2017-01-01

We explored potential associations between the strength of state Responsible Beverage Service (RBS) laws and self-reported binge drinking and alcohol-impaired driving in the U.S. A multilevel logistic mixed-effects model was used, adjusting for potential confounders. Analyses were conducted on the overall BRFSS sample and drinkers only. Seven percent of BRFSS respondents lived in states with the strongest RBS laws, 15% reported binge drinking and 2% reported driving after having too much to drink at least once in the past 30 days. There was no evidence of a significant association between RBS law strength and self-reported binge drinking or alcohol-impaired driving. Future studies should include additional information about RBS laws and use a prospective research design. PMID:29225382

Paternal and maternal alcohol abuse and offspring mental distress in the general population: the Nord-Trøndelag health study

PubMed Central

2012-01-01

Background The degree to which parental alcohol abuse is a risk factor for offspring mental distress is unclear, due to conflicting results of previous research. The inconsistencies in previous findings may be related to sample characteristics and lack of control of confounding or moderating factors. One such factor may be the gender of the abusing parent. Also, other factors, such as parental mental health, divorce, adolescent social network, school functioning or self-esteem, may impact the outcome. This study examines the impact of maternal and paternal alcohol abuse on adolescent mental distress, including potentially confounding, mediating or moderating effects of various variables. Methods Data from the Nord-Trøndelag Health Study (HUNT), a Norwegian population based health survey, from 4012 offspring and their parents were analyzed. Parental alcohol abuse was measured by numerical consumption indicators and CAGE, whereas offspring mental distress was measured by SCL-5, an abbreviated instrument tapping symptoms of anxiety and depression. Statistical method was analysis of variance. Results Maternal alcohol abuse was related to offspring mental distress, whereas no effect could be shown of paternal alcohol abuse. Effects of maternal alcohol abuse was partly mediated by parental mental distress, offspring social network and school functioning. However, all effects were relatively small. Conclusions The results indicate graver consequences for offspring of alcohol abusing mothers compared to offspring of alcohol abusing fathers. However, small effect sizes suggest that adolescent offspring of alcohol abusing parents in general manage quite well. PMID:22708789

What are the most effective risk-reduction strategies in sport concussion?

PubMed

Benson, Brian W; McIntosh, Andrew S; Maddocks, David; Herring, Stanley A; Raftery, Martin; Dvorák, Jirí

2013-04-01

To critically review the evidence to determine the efficacy and effectiveness of protective equipment, rule changes, neck strength and legislation in reducing sport concussion risk. Electronic databases, grey literature and bibliographies were used to search the evidence using Medical Subject Headings and text words. Inclusion/exclusion criteria were used to select articles for the clinical equipment studies. The quality of evidence was assessed using epidemiological criteria regarding internal/external validity (eg, strength of design, sample size/power, bias and confounding). No new valid, conclusive evidence was provided to suggest the use of headgear in rugby, or mouth guards in American football, significantly reduced players' risk of concussion. No evidence was provided to suggest an association between neck strength increases and concussion risk reduction. There was evidence in ice hockey to suggest fair-play rules and eliminating body checking among 11-years-olds to 12-years-olds were effective injury prevention strategies. Evidence is lacking on the effects of legislation on concussion prevention. Equipment self-selection bias was a common limitation, as was the lack of measurement and control for potential confounding variables. Lastly, helmets need to be able to protect from impacts resulting in a head change in velocities of up to 10 and 7 m/s in professional American and Australian football, respectively, as well as reduce head resultant linear and angular acceleration to below 50 g and 1500 rad/s(2), respectively, to optimise their effectiveness. A multifactorial approach is needed for concussion prevention. Future well-designed and sport-specific prospective analytical studies of sufficient power are warranted.

Double propensity-score adjustment: A solution to design bias or bias due to incomplete matching.

PubMed

Austin, Peter C

2017-02-01

Propensity-score matching is frequently used to reduce the effects of confounding when using observational data to estimate the effects of treatments. Matching allows one to estimate the average effect of treatment in the treated. Rosenbaum and Rubin coined the term "bias due to incomplete matching" to describe the bias that can occur when some treated subjects are excluded from the matched sample because no appropriate control subject was available. The presence of incomplete matching raises important questions around the generalizability of estimated treatment effects to the entire population of treated subjects. We describe an analytic solution to address the bias due to incomplete matching. Our method is based on using optimal or nearest neighbor matching, rather than caliper matching (which frequently results in the exclusion of some treated subjects). Within the sample matched on the propensity score, covariate adjustment using the propensity score is then employed to impute missing potential outcomes under lack of treatment for each treated subject. Using Monte Carlo simulations, we found that the proposed method resulted in estimates of treatment effect that were essentially unbiased. This method resulted in decreased bias compared to caliper matching alone and compared to either optimal matching or nearest neighbor matching alone. Caliper matching alone resulted in design bias or bias due to incomplete matching, while optimal matching or nearest neighbor matching alone resulted in bias due to residual confounding. The proposed method also tended to result in estimates with decreased mean squared error compared to when caliper matching was used.

Double propensity-score adjustment: A solution to design bias or bias due to incomplete matching

PubMed Central

2016-01-01

Propensity-score matching is frequently used to reduce the effects of confounding when using observational data to estimate the effects of treatments. Matching allows one to estimate the average effect of treatment in the treated. Rosenbaum and Rubin coined the term “bias due to incomplete matching” to describe the bias that can occur when some treated subjects are excluded from the matched sample because no appropriate control subject was available. The presence of incomplete matching raises important questions around the generalizability of estimated treatment effects to the entire population of treated subjects. We describe an analytic solution to address the bias due to incomplete matching. Our method is based on using optimal or nearest neighbor matching, rather than caliper matching (which frequently results in the exclusion of some treated subjects). Within the sample matched on the propensity score, covariate adjustment using the propensity score is then employed to impute missing potential outcomes under lack of treatment for each treated subject. Using Monte Carlo simulations, we found that the proposed method resulted in estimates of treatment effect that were essentially unbiased. This method resulted in decreased bias compared to caliper matching alone and compared to either optimal matching or nearest neighbor matching alone. Caliper matching alone resulted in design bias or bias due to incomplete matching, while optimal matching or nearest neighbor matching alone resulted in bias due to residual confounding. The proposed method also tended to result in estimates with decreased mean squared error compared to when caliper matching was used. PMID:25038071

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

PubMed Central

Wyss, Richard; Hansen, Ben B.; Ellis, Alan R.; Gagne, Joshua J.; Desai, Rishi J.; Glynn, Robert J.; Stürmer, Til

2017-01-01

Abstract A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the “dry-run” analysis, which divides the unexposed population into “pseudo-exposed” and “pseudo-unexposed” groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models. PMID:28338910

External adjustment sensitivity analysis for unmeasured confounding: an application to coronary stent outcomes, Pennsylvania 2004-2008.

PubMed

Huesch, Marco D

2013-06-01

Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004-2005 followed up for death through 3 years. Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. © Health Research and Educational Trust.

Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics.

PubMed

Ananth, Cande V; Schisterman, Enrique F

2017-08-01

Prospective and retrospective cohorts and case-control studies are some of the most important study designs in epidemiology because, under certain assumptions, they can mimic a randomized trial when done well. These assumptions include, but are not limited to, properly accounting for 2 important sources of bias: confounding and selection bias. While not adjusting the causal association for an intermediate variable will yield an unbiased estimate of the exposure-outcome's total causal effect, it is often that obstetricians will want to adjust for an intermediate variable to assess if the intermediate is the underlying driver of the association. Such a practice must be weighed in light of the underlying research question and whether such an adjustment is necessary should be carefully considered. Gestational age is, by far, the most commonly encountered variable in obstetrics that is often mislabeled as a confounder when, in fact, it may be an intermediate. If, indeed, gestational age is an intermediate but if mistakenly labeled as a confounding variable and consequently adjusted in an analysis, the conclusions can be unexpected. The implications of this overadjustment of an intermediate as though it were a confounder can render an otherwise persuasive study downright meaningless. This commentary provides an exposition of confounding bias, collider stratification, and selection biases, with applications in obstetrics and perinatal epidemiology. Copyright © 2017 Elsevier Inc. All rights reserved.

Does influenza vaccination improve pregnancy outcome? Methodological issues and research needs.

PubMed

Savitz, David A; Fell, Deshayne B; Ortiz, Justin R; Bhat, Niranjan

2015-11-25

Evidence that influenza vaccination during pregnancy is safe and effective at preventing influenza disease in women and their children through the first months of life is increasing. Several reports of reduced risk of adverse outcomes associated with influenza vaccination have generated interest in its potential for improving pregnancy outcome. Gavi, the Vaccine Alliance, estimates maternal influenza immunization programs in low-income countries would have a relatively modest impact on mortality compared to other new or under-utilized vaccines, however the impact would be substantially greater if reported vaccine effects on improved pregnancy outcomes were accurate. Here, we examine the available evidence and methodological issues bearing on the relationship between influenza vaccination and pregnancy outcome, particularly preterm birth and fetal growth restriction, and summarize research needs. Evidence for absence of harm associated with vaccination at a point in time is not symmetric with evidence of benefit, given the scenario in which vaccination reduces risk of influenza disease and, in turn, risk of adverse pregnancy outcome. The empirical evidence for vaccination preventing influenza in pregnant women is strong, but the evidence that influenza itself causes adverse pregnancy outcomes is inconsistent and limited in quality. Studies of vaccination and pregnancy outcome have produced mixed evidence of potential benefit but are limited in terms of influenza disease assessment and control of confounding, and their analytic methods often fail to fully address the longitudinal nature of pregnancy and influenza prevalence. We recommend making full use of results of randomized trials, re-analysis of existing observational studies to account for confounding and time-related factors, and quantitative assessment of the potential benefits of vaccination in improving pregnancy outcome, all of which should be informed by the collective engagement of experts in influenza, vaccines, and perinatal health. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The role of parenting in the prediction of criminal involvement: findings from a nationally representative sample of youth and a sample of adopted youth.

PubMed

Beaver, Kevin M; Schwartz, Joseph A; Connolly, Eric J; Al-Ghamdi, Mohammed Said; Kobeisy, Ahmed Nezar

2015-03-01

The role of parenting in the development of criminal behavior has been the source of a vast amount of research, with the majority of studies detecting statistically significant associations between dimensions of parenting and measures of criminal involvement. An emerging group of scholars, however, has drawn attention to the methodological limitations-mainly genetic confounding-of the parental socialization literature. The current study addressed this limitation by analyzing a sample of adoptees to assess the association between 8 parenting measures and 4 criminal justice outcome measures. The results revealed very little evidence of parental socialization effects on criminal behavior before controlling for genetic confounding and no evidence of parental socialization effects on criminal involvement after controlling for genetic confounding. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

PubMed

Tuk, Bert

2016-01-01

Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g ., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone-regardless of whether they present with syphilitic ALS or non-syphilitic ALS-may be effective at treating this rapidly progressive, highly devastating disease.

Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

PubMed

Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn

2016-11-01

It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up. © 2016 The British Psychological Society.

Effect of DHEAS on skeletal muscle over the life span: the InCHIANTI study.

PubMed

Valenti, Giorgio; Denti, Licia; Maggio, Marcello; Ceda, GianPaolo; Volpato, Stefano; Bandinelli, Stefania; Ceresini, Graziano; Cappola, Anne; Guralnik, Jack M; Ferrucci, Luigi

2004-05-01

It has been suggested that the reduced production of dehydroepiandrosterone sulfate (DHEAS) may be partially responsible for the decline of muscle strength and mass that often occurs with aging. However, this hypothesis has been only tested in small series of normal volunteers, with little consideration for potential confounders. Using data from a representative sample of 558 men (20-95 years) we tested the hypothesis that circulating DHEAS is independently associated with muscle strength and mass. Data are from InCHIANTI, an epidemiological study conducted in the Chianti geographic area (Tuscany, Italy). DHEAS serum levels were related to lower extremity muscle strength assessed by hand-held dynamometry and calf muscle area estimated from quantitative computerized tomography. Confounders included age, anthropometrics, physical activity, smoking, energy and alcohol intake, albumin, lipids, interleukin-6, comorbidity, depressive symptoms, and disability in activities of daily living. In fully adjusted models predicting lower extremity muscle strength and calf muscle area, we found significant age*log DHEAS interactions, suggesting that the relationship between DHEAS levels and muscle parameters differs across the life span. In age-stratified models adjusted for confounders, serum DHEAS was an independent predictor of muscle strength (p <.02) and mass (p <.01), but only for men between 60 and 79 years of age. After adjusting these models for serum-free or bioavailable testosterone, results were unchanged. In men aged 60-79 years, circulating DHEAS is an independent correlate of muscle strength and calf muscle area. The possible causal role of declining DHEAS in age-related sarcopenia should be further explored in longitudinal studies.

Comorbidities, confounders, and the white matter transcriptome in chronic alcoholism.

PubMed

Sutherland, Greg T; Sheedy, Donna; Sheahan, Pam J; Kaplan, Warren; Kril, Jillian J

2014-04-01

Alcohol abuse is the world's third leading cause of disease and disability, and one potential sequel of chronic abuse is alcohol-related brain damage (ARBD). This clinically manifests as cognitive dysfunction and pathologically as atrophy of white matter (WM) in particular. The mechanism linking chronic alcohol intoxication with ARBD remains largely unknown but it is also complicated by common comorbidities such as liver damage and nutritional deficiencies. Liver cirrhosis, in particular, often leads to hepatic encephalopathy (HE), a primary glial disease. In a novel transcriptomic study, we targeted the WM only of chronic alcoholics in an attempt to tease apart the pathogenesis of ARBD. Specifically, in alcoholics with and without HE, we explored both the prefrontal and primary motor cortices, 2 regions that experience differential levels of neuronal loss. Our results suggest that HE, along with 2 confounders, gray matter contamination, and low RNA quality are major drivers of gene expression in ARBD. All 3 exceeded the effects of alcohol itself. In particular, low-quality RNA samples were characterized by an up-regulation of translation machinery, while HE was associated with a down-regulation of mitochondrial energy metabolism pathways. The findings in HE alcoholics are consistent with the metabolic acidosis seen in this condition. In contrast non-HE alcoholics had widespread but only subtle changes in gene expression in their WM. Notwithstanding the latter result, this study demonstrates that significant confounders in transcriptomic studies of human postmortem brain tissue can be identified, quantified, and "removed" to reveal disease-specific signals. Copyright © 2014 by the Research Society on Alcoholism.

What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts.

PubMed

Brion, Marie-Jo A; Lawlor, Debbie A; Matijasevich, Alicia; Horta, Bernardo; Anselmi, Luciana; Araújo, Cora L; Menezes, Ana Maria B; Victora, Cesar G; Smith, George Davey

2011-06-01

A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low- or middle-income countries (LMIC), where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP), body mass index (BMI) and intelligence quotient (IQ). Standardized approaches for assessing the confounding structure of breastfeeding by socio-economic position were applied to the British Avon Longitudinal Study of Parents and Children (ALSPAC) (N ≃ 5000) and Brazilian Pelotas 1993 cohorts (N ≃ 1000). This was used to improve causal inference regarding associations of breastfeeding with child BP, BMI and IQ. Analyses were extended to include results from a meta-analysis of five LMICs (N ≃ 10 000) and compared with a randomized trial of breastfeeding promotion. Findings Although higher socio-economic position was strongly associated with breastfeeding in ALSPAC, there was little such patterning in Pelotas. In ALSPAC, breastfeeding was associated with lower BP, lower BMI and higher IQ, adjusted for confounders, but in the directions expected if due to socioeconomic patterning. In contrast, in Pelotas, breastfeeding was not strongly associated with BP or BMI but was associated with higher IQ. Differences in associations observed between ALSPAC and the LMIC meta-analysis were in line with those observed between ALSPAC and Pelotas, but with robust evidence of heterogeneity detected between ALSPAC and the LMIC meta-analysis associations. Trial data supported the conclusions inferred by the cross-cohort comparisons, which provided evidence for causal effects on IQ but not for BP or BMI. While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding, breastfeeding may have causal effects on IQ. Comparing associations between populations with differing confounding structures can be used to improve causal inference in observational studies.

Screen time impairs the relationship between physical fitness and academic attainment in children.

PubMed

Aguilar, Macarena M; Vergara, Felipe A; Velásquez, Erikson J A; Marina, Raquel; García-Hermoso, Antonio

2015-01-01

The purpose of this study was twofold: to analyze the association between physical fitness and academic attainment, and to determine the influence of screen time on the association between physical fitness and academic attainment. A cross-sectional study including 395 schoolchildren from seven schools of the Maule Region, Chile (mean age 12.1 years; 50.4% boys) participated in the autumn of 2014 (March to June). Self-reported physical activity and screen time were evaluated. The study measured academic achievement (mean of the grades obtained in several core subjects), physical fitness (cardiorespiratory fitness and muscular strength), weight, height, parental education, and socioeconomic status. Linear regression analysis was used to analyze the relationships between physical fitness and academic attainment after adjusting for potential confounders by gender. Analysis of variance was used to analyze the differences in academic attainment according to fitness and screen time categories (< 2 hours/day and ≥ 2 hours/day). In both genders good cardiorespiratory fitness levels were associated with high language (β=0.272-0.153) and mean academic attainment (β=0.192-0.156) grades; however, after adjusting for screen time and other potential confounders, these associations disappear. Similarly, no relationship was observed after analyzing those children who spend more hours of screen time (≥ 2 hours/day). Academic attainment is associated with higher cardiorespiratory fitness levels; however, it was weakly impaired by screen time. These findings seem to suggest that parents and policymakers should minimize the negative effects of screen time on children's lives to maximize the beneficial effect of healthy habits on academic attainment. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Booster Seat Effectiveness Among Older Children: Evidence From Washington State.

PubMed

Anderson, D Mark; Carlson, Lindsay L; Rees, Daniel I

2017-08-01

The American Academy of Pediatrics has recommended that children as old as 12 years use a booster seat when riding in motor vehicles, yet little is known about booster seat effectiveness when used by older children. This study estimated the association between booster use and injuries among children aged 8-12 years who were involved in motor vehicle crashes. Researchers analyzed data on all motor vehicle crashes involving children aged 8-12 years reported to the Washington State Department of Transportation from 2002 to 2015. Data were collected in 2015 and analyzed in 2016. Children who were in a booster seat were compared with children restrained by a seat belt alone. Logistic regression was used to adjust for potential confounders. In unadjusted models, booster use was associated with a 29% reduction in the odds of experiencing any injury versus riding in a seat belt alone (OR=0.709, 95% CI=0.675, 0.745). In models adjusted for potential confounders, booster use was associated with a 19% reduction in the odds of any injury relative to riding in a seat belt alone (OR=0.814, 95% CI=0.749, 0.884). The risk of experiencing an incapacitating/fatal injury was not associated with booster use. Children aged 8-12 years involved in a motor vehicle crash are less likely to be injured if in a booster than if restrained by a seat belt alone. Because only 10% of U.S. children aged 8-12 years use booster seats, policies encouraging their use could lead to fewer injuries. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

TBARS and BDNF levels in newborns exposed to crack/cocaine during pregnancy: a comparative study.

PubMed

Mardini, Victor; Rohde, Luis A; Ceresér, Keila M; Gubert, Carolina M; Silva, Emily G da; Xavier, Fernando; Parcianello, Rodrigo; Röhsig, Liane M; Pechansky, Flávio; Szobot, Claudia M

2017-01-01

To compare levels of a marker of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and brain-derived neurotrophic factor (BDNF) in umbilical cord blood (UCB) between newborns exposed to crack/cocaine in utero (exposed newborns [EN], n=57) and non-exposed newborns (NEN, n=99), as well as in maternal peripheral blood at delivery. This was a cross-sectional study. Potential confounders, including perinatal parameters, psychopathology, and use of other substances, were assessed. After adjusting for potential confounders, adjusted mean BDNF was significantly higher in EN (3.86 ng/mL, 95% confidence interval [95%CI] 2.29-5.43) than in NEN (0.85 ng/mL, 95%CI 0.47-1.23; p < 0.001; Cohen effect size: 1.12), and significantly lower in crack/cocaine mothers than in control mothers (4.03 ng/mL, 95%CI 2.87-5.18 vs. 6.67 ng/mL, 95%CI 5.60-7.74; p = 0.006). The adjusted mean TBARS level was significantly lower in EN (63.97 µM MDA, 95%CI 39.43-88.50) than NEN (177.04 µM MDA, 95%CI 140.93-213.14; p < 0.001; effect size = 0.84), with no difference between mother groups (p = 0.86). The changes in TBARS levels observed in EN suggest that fetuses exposed to cocaine mobilize endogenous antioxidant routes since very early stages of development. The increase in BDNF levels in EN might indicate changes in fetal development, whereas the changes in BDNF levels in mothers provide evidence of the complex metabolic processes involved in drug use during pregnancy.

Tea and Cardiovascular Disease

PubMed Central

Deka, Apranta; Vita, Joseph A.

2011-01-01

There is increasing evidence for a protective effect of tea consumption against cardiovascular disease. This review summarizes the available epidemiological data providing evidence for and against such an effect. We also review observational and intervention studies that investigated an effect of tea and tea extracts on cardiovascular risk factors, including blood pressure, serum lipids, diabetes mellitus, and obesity. Finally, we review potential mechanisms of benefit, including anti-inflammatory, anti-oxidant, and anti-proliferative effects, as well as favorable effects on endothelial function. Overall, the observational data suggest a benefit, but results are mixed and likely confounded by lifestyle and background dietary factors. The weight of evidence indicates favorable effects on risk factors and a number of plausible mechanisms have been elucidated in experimental and translational human studies. Despite the growing body evidence, it remains uncertain whether tea consumption should be recommended to the general population or to patients as a strategy to reduce cardiovascular risk. PMID:21477653

Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

PubMed

Plessinger, M A

1998-03-01

Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and the effects of amphetamine and methamphetamine in general.

Causal diagrams and multivariate analysis III: confound it!

PubMed

Jupiter, Daniel C

2015-01-01

This commentary concludes my series concerning inclusion of variables in multivariate analyses. We take up the issues of confounding and effect modification and summarize the work we have thus far done. Finally, we provide a rough algorithm to help guide us through the maze of possibilities that we have outlined. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Mediation analysis with time varying exposures and mediators

PubMed Central

VanderWeele, Tyler J.; Tchetgen Tchetgen, Eric J.

2016-01-01

Summary In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the “mediational g-formula.” When there is no mediation, the mediational g-formula reduces to Robins’ regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl’s mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators. PMID:28824285

Mediation analysis with time varying exposures and mediators.

PubMed

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

Long-term exposure to particulate matter, NO2 and the oxidative potential of particulates and diabetes prevalence in a large national health survey.

PubMed

Strak, Maciej; Janssen, Nicole; Beelen, Rob; Schmitz, Oliver; Vaartjes, Ilonca; Karssenberg, Derek; van den Brink, Carolien; Bots, Michiel L; Dijst, Martin; Brunekreef, Bert; Hoek, Gerard

2017-11-01

The evidence from observational epidemiological studies of a link between long-term air pollution exposure and diabetes prevalence and incidence is currently mixed. Some studies found the strongest associations of diabetes with fine particles, other studies with nitrogen dioxide and some studies found no associations. Our aim was to investigate associations between long-term exposure to multiple air pollutants and diabetes prevalence in a large national survey in the Netherlands. We performed a cross-sectional analysis using the 2012 Dutch national health survey to investigate the associations between the 2009 annual average concentrations of multiple air pollutants (PM 10 , PM 2.5 , PM 10-2.5 , PM 2.5 absorbance, OP DTT , OP ESR and NO 2 ) and diabetes prevalence, among 289,703 adults. Air pollution exposure was assessed by land use regression models. Diabetes was defined based on a combined measure of self-reported physician diagnosis and medication prescription from an external database. Using logistic regression, we adjusted for potential confounders, including neighborhood- and individual socio-economic status and lifestyle-related risk factors such as smoking habits, alcohol consumption, physical activity and BMI. After adjustment for potential confounders, all pollutants (except PM 2.5 ) were associated with diabetes prevalence. In two-pollutant models, NO 2 and OP DTT remained associated with increased diabetes prevalence. For NO 2 and OP DTT , single-pollutant ORs per interquartile range were 1.07 (95% CI: 1.05, 1.09) and 1.08 (95% CI: 1.05, 1.10), respectively. Stratified analysis showed no consistent effect modification by any of the included known diabetes risk factors. Long-term residential air pollution exposure was associated with diabetes prevalence in a large health survey in the Netherlands, strengthening the evidence of air pollution being an important diabetes risk factor. Most consistent associations were observed for NO 2 and oxidative potential of PM 2.5 measured by the DTT assay. The finding of an association with the oxidative potential of fine particles but not with PM 2.5 , suggests that particle composition may be important for a potential effect on diabetes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT

NASA Astrophysics Data System (ADS)

Maspero, Matteo; Seevinck, Peter R.; Schubert, Gerald; Hoesl, Michaela A. U.; van Asselen, Bram; Viergever, Max A.; Lagendijk, Jan J. W.; Meijer, Gert J.; van den Berg, Cornelis A. T.

2017-02-01

Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in the prostate. This study will be valuable for institutions interested in introducing MR-only dose planning in their clinical practice.

The association between paracetamol use and asthma: causation or coincidence?

PubMed

Weatherall, M; Ioannides, S; Braithwaite, I; Beasley, R

2015-01-01

A better understanding of the causation of asthma and allergic disorders could potentially lead to intervention strategies that reduce their prevalence and severity. One potential causative factor is the use of paracetamol. Most of the evidence for the link with asthma is from non-experimental studies of paracetamol exposure in utero, infancy, childhood and adult life; however, it has been difficult to rule out confounding and bias in the associations observed. The two randomized clinical trials of the effect of paracetamol in patients with asthma have been difficult to interpret, due to methodological issues. There have been no randomized controlled trials of paracetamol use and the development of asthma. Both asthma and paracetamol use are common, and so even if there is a relatively small effect of paracetamol exposure on the development of asthma or its severity, then such an effect would be of major public health significance. It is proposed that randomized controlled trials of the effect of paracetamol on the development of asthma and its severity are a high research priority. © 2014 John Wiley & Sons Ltd.

Social network effects in alcohol consumption among adolescents.

PubMed

Ali, Mir M; Dwyer, Debra S

2010-04-01

In this paper we seek to empirically quantify the role of peer social networks in explaining drinking behavior among adolescents. Using data from a nationally representative sample of adolescents we utilize a multivariate structural model with school-level fixed effects to account for the problems of contextual effects, correlated effects and peer selection to purge the potential biases from the estimates of peer influence. Our peer group measures are drawn not only from the nomination of close friends, but also from classmates. Drinking behavior among the peer groups was constructed using the peers' own report of their alcohol consumption. Controlling for parent level characteristics, and other demographic parameters, we find that a 10% increase in the proportion of classmates who drink will increase the likelihood of drinking participation and frequency by approximately four percentage points. We also find evidence to show that the influence of close friends, while still significant, diminishes in magnitude after accounting for unobserved environmental confounders. Our findings support the literature that peer effects are important determinants of drinking behavior even after controlling for potential biases. Effective policy aimed at reducing alcohol consumption among adolescents would consider these significant peer effects. 2009 Elsevier Ltd. All rights reserved.

Neurofeedback of SMR and Beta1 Frequencies: An Investigation of Learning Indices and Frequency-Specific Effects.

PubMed

Pimenta, Miguel G; van Run, Chris; de Fockert, Jan W; Gruzelier, John H

2018-05-15

Despite evidence that Sensorimotor Rhythm (SMR) and beta1 neurofeedback have distinct cognitive enhancement effects, it remains unclear whether their amplitudes can be independently enhanced. Furthermore, demands for top-down attention control, postural restraint and maintenance of cognitive set processes, all requiring low-beta frequencies, might masquerade as learning and confound interpretation. The feasibility of selectively enhancing SMR and beta1 amplitudes was investigated with the addition of a random frequency control condition that also requires the potentially confounding cognitive processes. A comprehensive approach to assessing neurofeedback learning was undertaken through the calculation of learning indices within- and across-session and pre-to-post baseline. Herein we provide the first demonstration of beta1 within-session amplitude learning that was not attributable to extraneous cognitive processes, for it was not found with random frequency training. On the other hand, within-session SMR learning might have been obscured by high interindividual variability and methodological limitations such as the type of feedback screen, the insufficient number of sessions, and the exclusion of simultaneous theta and high-beta inhibition. Interestingly, SMR and beta1 amplitude increased across sessions in the three groups suggesting unspecific effects of neurofeedback in the low beta frequency band. Moreover, there was no clear evidence of frequency specificity associated with either SMR or beta1 training. Some methodological limitations may underpin the divergent results with previous studies. Copyright © 2017 IBRO. All rights reserved.

Biomarkers for Uranium Risk Assessment for the Development of the CURE (Concerted Uranium Research in Europe) Molecular Epidemiological Protocol.

PubMed

Guéguen, Yann; Roy, Laurence; Hornhardt, Sabine; Badie, Christophe; Hall, Janet; Baatout, Sarah; Pernot, Eileen; Tomasek, Ladislav; Laurent, Olivier; Ebrahimian, Teni; Ibanez, Chrystelle; Grison, Stephane; Kabacik, Sylwia; Laurier, Dominique; Gomolka, Maria

2017-01-01

Despite substantial experimental and epidemiological research, there is limited knowledge of the uranium-induce health effects after chronic low-dose exposures in humans. Biological markers can objectively characterize pathological processes or environmental responses to uranium and confounding agents. The integration of such biological markers into a molecular epidemiological study would be a useful approach to improve and refine estimations of uranium-induced health risks. To initiate such a study, Concerted Uranium Research in Europe (CURE) was established, and involves biologists, epidemiologists and dosimetrists. The aims of the biological work package of CURE were: 1. To identify biomarkers and biological specimens relevant to uranium exposure; 2. To define standard operating procedures (SOPs); and 3. To set up a common protocol (logistic, questionnaire, ethical aspects) to perform a large-scale molecular epidemiologic study in uranium-exposed cohorts. An intensive literature review was performed and led to the identification of biomarkers related to: 1. retention organs (lungs, kidneys and bone); 2. other systems/organs with suspected effects (cardiovascular system, central nervous system and lympho-hematopoietic system); 3. target molecules (DNA damage, genomic instability); and 4. high-throughput methods for the identification of new biomarkers. To obtain high-quality biological materials, SOPs were established for the sampling and storage of different biospecimens. A questionnaire was developed to assess potential confounding factors. The proposed strategy can be adapted to other internal exposures and should improve the characterization of the biological and health effects that are relevant for risk assessment.

The effects of stress and affiliation on social decision-making: Investigating the tend-and-befriend pattern.

PubMed

Steinbeis, Nikolaus; Engert, Veronika; Linz, Roman; Singer, Tania

2015-12-01

The prevalence of psychosocial stress in Western societies is constantly on the rise. Its influence on social decision-making, however, remains poorly understood. Whereas, it is known that stress triggers psychological and physiological defense mechanisms, indications of such patterns in social decisions are ambivalent. We sought to elucidate the underlying mechanisms of stress-induced social decisions. We recruited 145 men, who were individually exposed to either a psychosocial stressor or a control condition, while primed with affiliation by interacting either with members of an in- or an out-group. We found that stressed participants were less trusting and engaged in less costly punishment compared to the non-stressed control group. Interacting with out-group members led to less reciprocity and more spiteful punishment. There was no interaction between stress and the affiliation conditions in any of the used social-decision-making paradigms. Lastly, while stress-reactive cortisol levels had no effect on trust behavior, higher baseline cortisol was correlated with greater trust. Our findings suggest that previous ambiguities in data reported on the influence of stress on social decisions, namely tend-and-befriend behavior may have arisen through critical social confounds in the induction of stress. When controlling for potential social confounds, stress may trigger fight-or-flight behavior as indicated by increased social anxiety. These findings highlight the considerable context-dependence of psychosocial stress and its effects on social behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

World War II-related post-traumatic stress disorder and breast cancer risk among Israeli women: a case-control study.

PubMed

Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

2014-03-01

Several studies have suggested that post-traumatic stress disorder (PTSD) is related to adverse health outcomes. There are limited data on PTSD and cancer, which has a long latency period. We investigated the association between World War II (WWII)-related PTSD and subsequent breast cancer (BC) risk among Jewish WWII survivors and examined whether this association was modified by exposure to hunger during WWII. We compared 65 BC patients diagnosed in 2005 through 2010 to 200 population-based controls who were members of various organizations for Jewish WWII survivors in Israel. All participants were born in Europe, lived at least six months under Nazi rule during WWII, and immigrated to Israel after the war. We estimated PTSD using the PTSD Inventory and applied logistic regression models to estimate the association between WWII-related PTSD and BC, adjusting for potential confounders. We observed a linear association between WWII-related PTSD and BC risk. This association remained significant following adjustment for potential confounders, including obesity, alcohol consumption, smoking, age during WWII, hunger exposure during WWII, and total number of traumatic life events (OR = 2.89, 95% CI = 1.14-7.31). However, the level of hunger exposure during WWII modified this effect significantly. These findings suggest an independent association between WWII-related PTSD and subsequent BC risk in Jewish WWII survivors that is modified by hunger, a novel finding. Future research is needed to further explore these findings.

A Cross-Sectional Study of the Association between Autoantibodies and Qualitative Ultrasound Index of Bone in an Elderly Sample without Clinical Autoimmune Disease

PubMed Central

McEvoy, Mark; Kelly, Brian; Agnew, Linda; Walker, Frederick R.; Boyle, Michael

2018-01-01

Bone loss is characteristic of the ageing process and a common complication of many autoimmune diseases. Research has highlighted a potential role of autoantibodies in pathologic bone loss. The confounding effects of immunomodulatory drugs make it difficult to establish the contribution of autoantibodies amongst autoimmune disease sufferers. We attempted to examine the relationship between autoantibodies and bone mass in a population of 2812 elderly participants without clinical autoimmune disease. Serum samples were assayed for a panel of autoantibodies (anti-nuclear, extractable nuclear antigen, anti-neutrophil cytoplasmic, thyroid peroxidase, tissue transglutaminase, anti-cardiolipin, rheumatoid factor, and cyclic citrullinated peptide). Bone mass was measured using quantitative ultrasound (QUS) of the calcaneus. The relationship between each autoantibody and bone mass was determined using linear regression models. Anti-nuclear autoantibodies were the most prevalent, positive in approximately 11%, and borderline in roughly 23% of our sample. They were also the only autoantibody observed to be significantly associated with QUS index in the univariate analysis (n = 1628; r = −0.20; 95% CI: −0.40–0.00; p = 0.046). However, statistical significance was lost after adjustment for various other potential confounders. None of the other autoantibodies was associated with QUS index in either univariate or multivariate analysis. We are limited by the cross-sectional nature of the study and the low prevalence of autoantibodies in our nonclinical sample. PMID:29854851

Adaptive dimensions of health research among indigenous Siberians.

PubMed

Snodgrass, J Josh; Sorensen, Mark V; Tarskaia, Larissa A; Leonard, William R

2007-01-01

Present evidence suggests that modern humans were the first hominid species to successfully colonize high-latitude environments (> or =55 degrees N). Given evidence for a recent (<200,000 years) lower latitude naissance of modern humans, the global dispersal and successful settlement of arctic and subarctic regions represent an unprecedented adaptive shift. This adaptive shift, which included cultural, behavioral, and biological dimensions, allowed human populations to cope with the myriad environmental stressors encountered in circumpolar regions. Although unique morphological and physiological adaptations among contemporary northern residents have been recognized for decades, human biologists are only now beginning to consider whether biological adaptations to regional environmental conditions influence health changes associated with economic modernization and lifestyle change. Recent studies have documented basal metabolic rates (BMRs) among indigenous Siberian populations that are systematically elevated compared to lower latitude groups; this metabolic elevation apparently is a physiological adaptation to cold stress experienced in the circumpolar environment. Important health implications of metabolic adaptation are suggested by research with the Yakut (Sakha), Evenki, and Buriat of Siberia. BMR is significantly positively correlated with blood pressure, independently of body size, body composition, and various potentially confounding variables (e.g., age and smoking). Further, this research has documented a significant negative association between BMR and LDL cholesterol, which remains after controlling for potential confounders; this suggests that high metabolic turnover among indigenous Siberians has a protective effect with regard to plasma lipid levels. These results underscore the importance of incorporating an evolutionary approach into health research among northern populations.

Voluntary psychiatric emergencies in Los Angeles County after funding of California's Mental Health Services Act.

PubMed

Bruckner, Tim A; Yonsu, Kim; Chakravarthy, Bharath; Brown, Timothy Tyler

2012-08-01

Since 2006, California's Mental Health Services Act (MHSA) has distributed an estimated $6 billion in new tax revenues to county mental health systems. Although evaluations of MHSA's effectiveness find favorable outcomes among high-risk individuals that represent 6% of all mental health clients, scant research has tested whether MHSA funds improve the overall functioning of the public mental health system. The authors analyzed whether the incidence of voluntary emergency psychiatric visits, a key gauge of the functioning of the mental health system, fell below expected levels after the disbursement of MHSA funds. Los Angeles County, the most populous county in California, was examined. The authors obtained the monthly incidence of emergency psychiatric visits among Medi-Cal patients for 96 months spanning July 2000 to June 2008 (5.9 million overall admissions, of which 47,328 were emergency visits). Time-series methods controlled for temporal patterns in emergency visits as well as other potential confounders (unemployment, for example) that could induce spurious associations. The incidence of voluntary psychiatric emergencies fell below expected levels eight to 12 months after the disbursement of MHSA funds. After one year, emergency visits returned to their long-term mean level. Results remained robust after analyses controlled for outliers and potential confounders. In the short term, an infusion of public funds devoted to mental health services appeared to reduce psychiatric emergency visits. Explanations for the transient nature of the decline in emergency visits in Los Angeles County are discussed.

Minimum Wage and Overweight and Obesity in Adult Women: A Multilevel Analysis of Low and Middle Income Countries.

PubMed

Conklin, Annalijn I; Ponce, Ninez A; Frank, John; Nandi, Arijit; Heymann, Jody

2016-01-01

To describe the relationship between minimum wage and overweight and obesity across countries at different levels of development. A cross-sectional analysis of 27 countries with data on the legislated minimum wage level linked to socio-demographic and anthropometry data of non-pregnant 190,892 adult women (24-49 y) from the Demographic and Health Survey. We used multilevel logistic regression models to condition on country- and individual-level potential confounders, and post-estimation of average marginal effects to calculate the adjusted prevalence difference. We found the association between minimum wage and overweight/obesity was independent of individual-level SES and confounders, and showed a reversed pattern by country development stage. The adjusted overweight/obesity prevalence difference in low-income countries was an average increase of about 0.1 percentage points (PD 0.075 [0.065, 0.084]), and an average decrease of 0.01 percentage points in middle-income countries (PD -0.014 [-0.019, -0.009]). The adjusted obesity prevalence difference in low-income countries was an average increase of 0.03 percentage points (PD 0.032 [0.021, 0.042]) and an average decrease of 0.03 percentage points in middle-income countries (PD -0.032 [-0.036, -0.027]). This is among the first studies to examine the potential impact of improved wages on an important precursor of non-communicable diseases globally. Among countries with a modest level of economic development, higher minimum wage was associated with lower levels of obesity.

Maternal Use of Corporal Punishment for 3-year-old Children and Subsequent Risk for Child Aggressive Behavior

PubMed Central

Taylor, Catherine A.; Manganello, Jennifer A.; Lee, Shawna J.; Rice, Janet C.

2016-01-01

OBJECTIVE To examine the association between maternal use of corporal punishment (CP) against their 3-year-old children and subsequent aggressive behavior among those children two years later. METHODS Respondents participated in waves 1, 3, and 5 of the Fragile Families and Child Wellbeing Study (1998–2005), a population-based longitudinal birth cohort study of children (and their parents) born in one of 20 large U.S. cities (n=2,461), with oversampling of unmarried couples. Maternal reports of CP, children’s aggressive behaviors at 3 and 5 years of age, and a host of key demographics and potential confounding factors were assessed including: child physical maltreatment, psychological maltreatment, and neglect, intimate partner aggression and violence, and maternal stress, depression, substance use, and consideration of abortion. RESULTS Multiple logistic regression analyses revealed that frequent use of CP (i.e., maternal use of spanking more than twice in the prior month) when the child was 3 years-old was associated with increased risk for higher levels of child aggression when the child was 5 years-old (adjusted odds ratio = 1.49 [CI=1.2–1.8] p<0.0001), even after simultaneously controlling for the child’s level of aggression at 3 years of age as well as all of the aforementioned confounding factors and key demographics. CONCLUSIONS Despite American Academy of Pediatrics recommendations to the contrary, most parents in the U.S. approve of and have used CP as a form of child discipline. The current findings support a growing body of evidence that even minor forms of CP, such as spanking, raise risk for increased subsequent child aggressive behavior. Importantly, these findings cannot be attributed to the possible confounding effects of a host of other maternal parenting risk factors. Increased and improved efforts to reduce the use of CP and promote the use of alternative, effective non-physical forms of child discipline among U.S. parents are warranted. PMID:20385647

Uncovering cyanobacteria ecological networks from long-term monitoring data using Granger causality analysis

NASA Astrophysics Data System (ADS)

Nelson, N.; Munoz-Carpena, R.; Kaplan, D. A.; Phlips, E. J.

2016-12-01

In many aquatic systems, cyanobacteria form harmful blooms capable of producing toxins, prompting hypoxia, and/or introducing internal nitrogen loads via N2-fixation, among other impacts. Traditionally, system-specific cyanobacteria drivers are determined by performing controlled experiments and bioassays, but these approaches may neglect the influences of confounding factors and over assign importance to only those variables considered within experimental designs. For example, a bioassay may conclude that the cyanobacteria in a particular system are limited by phosphorus, but will not explicitly take into account the role of flow as a control on phosphorus delivery. This study aims to address this analytical gap by identifying environmental controls on cyanobacteria while removing the effects of potentially confounding variables. In the present work, we evaluate a unique long-term (17 year) dataset composed of monthly observations of phytoplankton and zooplankton species abundances, water quality constituents, and hydrologic variables from Lake George, a flow-through lake of the St. Johns River (FL) impacted by cyanobacterial blooms. Using conditional Granger causality analysis, a time series approach that infers causality while removing the effects of confounding variables, data were evaluated to identify biological and physicochemical drivers of cyanobacteria. The analysis was performed for three response variable sets: total cyanobacteria, N2-fixers and non-fixers, and cyanobacteria genera. Results depicted increasing levels of ecological complexity as subdivisions of cyanobacteria became more detailed; whereas causal networks produced from analyses of cyanobacteria genera provided novel insights relevant for management (i.e. nutrients, flow), the total cyanobacteria network only included water temperature as a significant driver. Additionally, the more detailed cyanobacteria subdivisions uncovered that N2-fixation was only evident with the earliest season bloomer, thus indicating that early season bloomers may be facilitating later-season growth. These findings highlight the importance of detailed monitoring efforts, and indicate that greater emphasis needs to be placed on the role of early bloomers in phytoplankton dynamics, as it relates to management efforts.

Protective Effect of Hydroxychloroquine on Renal Damage in Patients with Lupus Nephritis: Data from LUMINA, a Multiethnic U.S. Cohort

PubMed Central

Pons-Estel, Guillermo J.; Alarcón, Graciela S.; McGwin, Gerald; Danila, Maria I.; Zhang, Jie; Bastian, Holly M.; Reveille, John D.; Vilá, Luis M.

2010-01-01

Objective To assess if hydroxychloroquine can delay renal damage development in lupus nephritis patients. Methods Lupus nephritis patients (n=256) from LUMINA (n=635), a multiethnic cohort of African Americans, Hispanics and Caucasians, age ≥16 years, disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined per the SLICC Damage Index (≥1 of the following lasting at least six months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria ≥3.5 g and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n=53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potentially confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or World Health Organization (WHO) Class glomerulonephritis were also derived. Results Sixty-three (31.0%) of 203 patients developed renal damage over a mean (standard deviation) disease duration of 5.2 (3.5) years. The most frequent renal damage domain item was proteinuria. Hydroxychloroquine-takers (79.3%) exhibited a lower frequency of WHO Class IV glomerulonephritis, lower disease activity and received lower glucocorticoid doses than non-takers. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (HR=0.12; 95% CI 0.02-0.97; p=0.0464) and reduced (HR=0.29; 95%CI 0.13-0.68; p=0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in hydroxychloroquine non-takers and in WHO Class IV glomerulonephritis (p<0.0001). Conclusions After adjusting for possible confounding factors the protective effect of hydroxychloroquine in retarding renal damage occurrence in SLE is still evident. PMID:19479701

Marijuana use and car crash injury.

PubMed

Blows, Stephanie; Ivers, Rebecca Q; Connor, Jennie; Ameratunga, Shanthi; Woodward, Mark; Norton, Robyn

2005-05-01

To investigate the relationship between marijuana use prior to driving, habitual marijuana use and car crash injury. Population based case-control study in Auckland, New Zealand. Case vehicles were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and control vehicles were a random sample of cars driving on Auckland roads. The drivers of 571 case and 588 control vehicles completed a structured interview. Self reported marijuana use in the 3 hours prior to the crash/survey and habitual marijuana use over the previous 12 months were recorded, along with a range of other variables potentially related to crash risk. The main outcome measure was hospitalization or death of a vehicle occupant due to car crash injury. Acute marijuana use was significantly associated with car crash injury, after controlling for the confounders age, gender, ethnicity, education level, passenger carriage, driving exposure and time of day (OR 3.9, 95% CI 1.2-12.9). However, after adjustment for these confounders plus other risky driving at the time of the crash (blood alcohol concentration, seat-belt use, travelling speed and sleepiness score), the effect of acute marijuana intake was no longer significant (OR 0.8, 95% CI 0.2-3.3). There was a strong significant association between habitual use and car crash injury after adjustment for all the above confounders plus acute use prior to driving (OR 9.5, 95% CI 2.8-32.3). This population-based case-control study indicates that habitual use of marijuana is strongly associated with car crash injury. The nature of the relationship between marijuana use and risk-taking is unclear and needs further research. The prevalence of marijuana use in this driving population was low, and acute use was associated with habitual marijuana use, suggesting that intervention strategies may be more effective if they are targeted towards high use groups.

Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

PubMed

Anderson, D

2001-09-01

It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which affect them is complex. Sometimes the variables are not completely independent of each other.

Epidemiologic studies of electric and magnetic fields and cancer: Strategies for extending knowledge

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

Savitz, D.A.

1993-12-01

Epidemiologic research concerning electric and magnetic fields in relation to cancer has focused on the potential etiologic roles of residential exposure on childhood cancer and occupational exposure on adult leukemia and brain cancer. Future residential studies must concentrate on exposure assessment that is enhanced by developing models of historical exposure, assessment of the relation between magnetic fields and wire codes, and consideration of alternate exposure indices. Study design issues deserving attention include possible biases in random digit dialing control selection, consideration of the temporal course of exposure and disease, and acquisition of the necessary information to assess the potential valuemore » of ecologic studies. Highest priorities are comprehensive evaluation of exposure patterns and sources and examination of the sociology and geography of residential wire codes. Future occupational studies should also concentrate on improved exposure assessment with increased attention to nonutility worker populations and development of historical exposure indicators that are superior to job titles alone. Potential carcinogens in the workplace that could act as confounders need to be more carefully examined. The temporal relation between exposure and disease and possible effect modification by other workplace agents should be incorporated into future studies. The most pressing need is for measurement of exposure patterns in a variety of worker populations and performance of traditional epidemiologic evaluations of cancer occurrence. The principal source of bias toward the null is nondifferential misclassification of exposure with improvements expected to enhance any true etiologic association that is present. Biases away from the null might include biased control selection in residential studies and chemical carcinogens acting as confounders in occupational studies. 51 refs., 1 tab.« less

[CONSUMPTION OF OMEGA- 3 FATTY ACIDS AND DEPRESSIVE SYMPTOMS IN COLLEGE STUDENTS FROM SONORA, MEXICO].

PubMed

Rubi Vargas, María; González Lomelí, Daniel; Terrazas Medina, Efraín A; Peralta Peña, Sandra L; Jordán Jinez, Ma Lourdes; Ruiz Paloalto, Ma Laura; Cupul Uicab, Lea A

2015-10-01

recent studies suggest that low serum levels of polyunsaturated fatty acids omega-3 are associated with a higher prevalence of depression. to evaluate whether low consumption of Omega-3 fatty acids is associated with a higher prevalence of depressive symptoms in a sample of college students from the Northwest of Mexico, and to assess the potential effect modification by alcohol consumption. we conducted a cross-sectional study in a sample of 706 college students (males and females) aged 18 to 24. The presence of depressive symptoms was identified with the Depression Scale of the Center for Epidemiologic Studies (CES-D), using a cutoff point of ≥ 24. The intake of omega-3 was obtained by a food frequency questionnaire validated for Mexican population. We estimated the weekly intake of alpha-linolenic fatty acid (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) derived from the diet in mg/g of food. The association between omega-3 from diet and the presence of depressive symptoms was assessed using logistic regression models adjusted for potential confounders. 67% of the participants were females; 16.6% were classified as having depressive symptoms. A low intake of ALA and EPA + DHA was not associated with depressive symptoms before and after adjusting for confounders. Median levels of ALA (from nuts only) were significantly lower among those with depressive symptoms compared to those without these symptoms. in this population of Mexican college students, a low intake of omega-3 fatty acids was not associated with depressive symptoms. The potential association between nut consumption and depressive symptoms deserve more attention. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Effects of spectral smearing on performance of the spectral ripple and spectro-temporal ripple tests.

PubMed

Narne, Vijaya Kumar; Sharma, Mridula; Van Dun, Bram; Bansal, Shalini; Prabhu, Latika; Moore, Brian C J

2016-12-01

The main aim of this study was to use spectral smearing to evaluate the efficacy of a spectral ripple test (SRt) using stationary sounds and a recent variant with gliding ripples called the spectro-temporal ripple test (STRt) in measuring reduced spectral resolution. In experiment 1 the highest detectable ripple density was measured using four amounts of spectral smearing (unsmeared, mild, moderate, and severe). The thresholds worsened with increasing smearing and were similar for the SRt and the STRt across the three conditions with smearing. For unsmeared stimuli, thresholds were significantly higher (better) for the STRt than for the SRt. An amplitude fluctuation at the outputs of simulated (gammatone) auditory filters centered above 6400 Hz was identified as providing a potential detection cue for the STRt stimuli. Experiment 2 used notched noise with energy below and above the passband of the SRt and STRt stimuli to reduce confounding cues in the STRt. Thresholds were almost identical for the STRt and SRt for both unsmeared and smeared stimuli, indicating that the confounding cue for the STRt was eliminated by the notched noise. Thresholds obtained with notched noise present could be predicted reasonably accurately using an excitation-pattern model.

Estimating Causal Effects in Observational Studies using Electronic Health Data: Challenges and (Some) Solutions

PubMed Central

Stuart, Elizabeth A.; DuGoff, Eva; Abrams, Michael; Salkever, David; Steinwachs, Donald

2013-01-01

Electronic health data sets, including electronic health records (EHR) and other administrative databases, are rich data sources that have the potential to help answer important questions about the effects of clinical interventions as well as policy changes. However, analyses using such data are almost always non-experimental, leading to concerns that those who receive a particular intervention are likely different from those who do not in ways that may confound the effects of interest. This paper outlines the challenges in estimating causal effects using electronic health data and offers some solutions, with particular attention paid to propensity score methods that help ensure comparisons between similar groups. The methods are illustrated with a case study describing the design of a study using Medicare and Medicaid administrative data to estimate the effect of the Medicare Part D prescription drug program on individuals with serious mental illness. PMID:24921064

Recent Approaches to Estimate Associations Between Source-Specific Air Pollution and Health.

PubMed

Krall, Jenna R; Strickland, Matthew J

2017-03-01

Estimating health effects associated with source-specific exposure is important for better understanding how pollution impacts health and for developing policies to better protect public health. Although epidemiologic studies of sources can be informative, these studies are challenging to conduct because source-specific exposures (e.g., particulate matter from vehicles) often are not directly observed and must be estimated. We reviewed recent studies that estimated associations between pollution sources and health to identify methodological developments designed to address important challenges. Notable advances in epidemiologic studies of sources include approaches for (1) propagating uncertainty in source estimation into health effect estimates, (2) assessing regional and seasonal variability in emissions sources and source-specific health effects, and (3) addressing potential confounding in estimated health effects. Novel methodological approaches to address challenges in studies of pollution sources, particularly evaluation of source-specific health effects, are important for determining how source-specific exposure impacts health.

Economic downturns and suicide mortality in the USA, 1980-2010: observational study.

PubMed

Harper, Sam; Charters, Thomas J; Strumpf, Erin C; Galea, Sandro; Nandi, Arijit

2015-06-01

Several studies have suggested strong associations between economic downturns and suicide mortality, but are at risk of bias due to unmeasured confounding. The rationale for our study was to provide more robust evidence by using a quasi-experimental design. We analysed 955,561 suicides occurring in the USA from 1980 to 2010 and used a broad index of economic activity in each US state to measure economic conditions. We used a quasi-experimental, fixed-effects design and we also assessed whether the effects were heterogeneous by demographic group and during periods of official recession. After accounting for secular trends, seasonality and unmeasured fixed characteristics of states, we found that an economic downturn similar in magnitude to the 2007 Great Recession increased suicide mortality by 0.14 deaths per 100,000 population [95% confidence interval (CI) 0.00, 0.28] or around 350 deaths. Effects were stronger for men (0.28, 95% CI 0.07, 0.49) than women and for those with less than 12 years of education (1.22 95% CI 0.83, 1.60) compared with more than 12 years of education. The overall effect did not differ for recessionary (0.11, 95% CI -0.02, 0.25) vs non-recessionary periods (0.15, 95% CI 0.01, 0.29). The main study limitation is the potential for misclassified death certificates and we cannot definitively rule out unmeasured confounding. We found limited evidence of a strong, population-wide detrimental effect of economic downturns on suicide mortality. The overall effect hides considerable heterogeneity by gender, socioeconomic position and time period. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Effort--reward imbalance and medically certified absence for mental health problems: a prospective study of white-collar workers.

PubMed

Ndjaboué, R; Brisson, C; Vézina, M; Blanchette, C; Bourbonnais, R

2014-01-01

Little is known about the effects of psychosocial work factors on objectively assessed mental health problems leading to medically certified absence. Only one study has evaluated the prospective effects of effort-reward imbalance (ERI) at work with regards to this outcome. The present study aimed to evaluate the effects of ERI on the incidence of medically certified absence for mental health problems. The study included 2086 white-collar workers (63.3% women) employed in public organisations in Quebec city. Participants were followed over a 9-year period. Medical absences from work were collected from employers' files and psychosocial factors were measured using the ERI questionnaire. Cox regression models were used to estimate the incidence of certified sickness absence due to mental health problems that lasted 5 workdays or more, while controlling for confounders. Workers exposed to ERI had a higher risk of a first spell of medically certified absence for mental health problems (HR=1.38, 95% CI 1.08 to 1.76) compared with unexposed workers. Low reward was significantly associated with a high risk among men (HR=2.80, 95% CI 1.34 to 5.89) but not in women. (HR=1.24, 95% CI 0.90 to 1.73). Effort at work had no effect on certified absence. All these effects were adjusted for potential confounders. ERI and low reward at work were prospectively associated with medically certified absence for mental health problems. These effects seem to differ by gender. Primary prevention that is aimed at reducing these stressors should be considered to help reduce the incidence of such severe mental health problems.

Economic downturns and suicide mortality in the USA, 1980–2010: observational study

PubMed Central

Harper, Sam; Charters, Thomas J; Strumpf, Erin C; Galea, Sandro; Nandi, Arijit

2015-01-01

Background: Several studies have suggested strong associations between economic downturns and suicide mortality, but are at risk of bias due to unmeasured confounding. The rationale for our study was to provide more robust evidence by using a quasi-experimental design. Methods: We analysed 955 561 suicides occurring in the USA from 1980 to 2010 and used a broad index of economic activity in each US state to measure economic conditions. We used a quasi-experimental, fixed-effects design and we also assessed whether the effects were heterogeneous by demographic group and during periods of official recession. Results: After accounting for secular trends, seasonality and unmeasured fixed characteristics of states, we found that an economic downturn similar in magnitude to the 2007 Great Recession increased suicide mortality by 0.14 deaths per 100 000 population [95% confidence interval (CI) 0.00, 0.28] or around 350 deaths. Effects were stronger for men (0.28, 95% CI 0.07, 0.49) than women and for those with less than 12 years of education (1.22 95% CI 0.83, 1.60) compared with more than 12 years of education. The overall effect did not differ for recessionary (0.11, 95% CI −0.02, 0.25) vs non-recessionary periods (0.15, 95% CI 0.01, 0.29). The main study limitation is the potential for misclassified death certificates and we cannot definitively rule out unmeasured confounding. Conclusions: We found limited evidence of a strong, population-wide detrimental effect of economic downturns on suicide mortality. The overall effect hides considerable heterogeneity by gender, socioeconomic position and time period. PMID:26082407

Effects of aggregation of drug and diagnostic codes on the performance of the high-dimensional propensity score algorithm: an empirical example.

PubMed

Le, Hoa V; Poole, Charles; Brookhart, M Alan; Schoenbach, Victor J; Beach, Kathleen J; Layton, J Bradley; Stürmer, Til

2013-11-19

The High-Dimensional Propensity Score (hd-PS) algorithm can select and adjust for baseline confounders of treatment-outcome associations in pharmacoepidemiologic studies that use healthcare claims data. How hd-PS performance is affected by aggregating medications or medical diagnoses has not been assessed. We evaluated the effects of aggregating medications or diagnoses on hd-PS performance in an empirical example using resampled cohorts with small sample size, rare outcome incidence, or low exposure prevalence. In a cohort study comparing the risk of upper gastrointestinal complications in celecoxib or traditional NSAIDs (diclofenac, ibuprofen) initiators with rheumatoid arthritis and osteoarthritis, we (1) aggregated medications and International Classification of Diseases-9 (ICD-9) diagnoses into hierarchies of the Anatomical Therapeutic Chemical classification (ATC) and the Clinical Classification Software (CCS), respectively, and (2) sampled the full cohort using techniques validated by simulations to create 9,600 samples to compare 16 aggregation scenarios across 50% and 20% samples with varying outcome incidence and exposure prevalence. We applied hd-PS to estimate relative risks (RR) using 5 dimensions, predefined confounders, ≤ 500 hd-PS covariates, and propensity score deciles. For each scenario, we calculated: (1) the geometric mean RR; (2) the difference between the scenario mean ln(RR) and the ln(RR) from published randomized controlled trials (RCT); and (3) the proportional difference in the degree of estimated confounding between that scenario and the base scenario (no aggregation). Compared with the base scenario, aggregations of medications into ATC level 4 alone or in combination with aggregation of diagnoses into CCS level 1 improved the hd-PS confounding adjustment in most scenarios, reducing residual confounding compared with the RCT findings by up to 19%. Aggregation of codes using hierarchical coding systems may improve the performance of the hd-PS to control for confounders. The balance of advantages and disadvantages of aggregation is likely to vary across research settings.

Famine Exposure in the Young and the Risk of Type 2 Diabetes in Adulthood

PubMed Central

van Abeelen, Annet F.M.; Elias, Sjoerd G.; Bossuyt, Patrick M.M.; Grobbee, Diederick E.; van der Schouw, Yvonne T.; Roseboom, Tessa J.; Uiterwaal, Cuno S.P.M.

2012-01-01

The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased type 2 diabetes risk in adulthood. We investigated the association between undernutrition during childhood and young adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect-EPIC (European Prospective Investigation Into Cancer and Nutrition) who were exposed to the 1944–1945 Dutch famine when they were between age 0 and 21 years. We used Cox proportional hazards regression models to explore the effect of famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education. Self-reported famine exposure during childhood and young adulthood was associated with an increased type 2 diabetes risk in a dose-dependent manner. In those who reported moderate famine exposure, the age-adjusted type 2 diabetes hazard ratio (HR) was 1.36 (95% CI [1.09–1.70]); in those who reported severe famine exposure, the age-adjusted HR was 1.64 (1.26–2.14) relative to unexposed women. These effects did not change after adjustment for confounders. This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases type 2 diabetes risk in adulthood. PMID:22648386

Effect of Acetaminophen on the Prevention of Acute Kidney Injury in Patients With Sepsis.

PubMed

Patanwala, Asad E; Aljuhani, Ohoud; Bakhsh, Hussain; Erstad, Brian L

2018-01-01

Acute kidney injury (AKI) commonly occurs in patients with sepsis. Acetaminophen (APAP) has been shown to inhibit lipid peroxidation and, thus, may be renal protective in patients with sepsis. The objective of this study was to determine the effect of APAP on AKI in patients with sepsis. This was a retrospective cohort study conducted at 2 affiliated academic medical centers in the United States. Adult patients who were admitted to the intensive care unit with a diagnosis of severe sepsis were included. Patients were categorized based on whether APAP was received within the first 7 days of hospitalization (APAP or no APAP groups). The primary outcome measure was occurrence or increase in AKI stage from admission. Multivariate logistic regression analyses were used to adjust for potential confounders. There were 238 patients who were included in the study cohort. Of these, 122 received APAP and 116 did not receive APAP. AKI or exacerbation occurred in 16.4% (n = 20) of patients in the APAP group and 19.8% (n = 23) of patients in the no APAP group ( P = 0.505). After adjusting for the most important confounders, there was no significant association between APAP use and AKI (odds ratio = 1.2; 95% CI = 0.6-2.4; P = 0.639). APAP use in critically ill patients with sepsis may not reduce the occurrence or exacerbation of AKI.

A seroprevalence and descriptive epidemiological study of malaria among Indian tribes of the Amazon basin of Brazil.

PubMed

de Arruda, M E; Aragaki, C; Gagliardi, F; Haile, R W

1996-04-01

Data on the seroprevalences of Plasmodium falciparum, P. vivax, and P. malariae in four isolated Indian tribes of the Amazon basin in Brazil, as determined by IFAT, were re-analysed. Age-, sex- and tribe-specific geometric mean antibody titres and externally standardized prevalence ratios were calculated for each parasite species. Correlation coefficients and prevalence odds ratios were also calculated for multiple infections with different combinations of the three Plasmodium species. Titres of all but one of the antibodies studied were similar in males and females; titres of antibodies to the blood stages of P. malariae were slightly higher in females than in males. Titres of antibodies to all three Plasmodium species increased with subject age, and this age effect was not confounded by sex or tribal differences. There were striking differences between tribes, with the Parakana tribe having relatively low titres of antibodies against P. falciparum and P. malariae; these tribal effects were not confounded by sex or age differences between tribes. The results indicate that conditions conductive to the transmission of P. malariae exist in this region of the Amazon. The potential for zoonotic transmission of P. brasilianum, a parasite of monkeys which is morphologically similar to P. malarie, and the generally high rates of seropositivity to all three species of Plasmodium indicate that control measures which are adequate and applicable to the region studied need to be developed.

Conditions Affecting Social Space in Drosophila melanogaster.

PubMed

McNeil, Alison R; Jolley, Sam N; Akinleye, Adesanya A; Nurilov, Marat; Rouzyi, Zulekha; Milunovich, Austin J; Chambers, Moria C; Simon, Anne F

2015-11-05

The social space assay described here can be used to quantify social interactions of Drosophila melanogaster - or other small insects - in a straightforward manner. As we previously demonstrated (1), in a two-dimensional chamber, we first force the flies to form a tight group, subsequently allowing them to take their preferred distance from each other. After the flies have settled, we measure the distance to the closest neighbor (or social space), processing a static picture with free online software (ImageJ). The analysis of the distance to the closest neighbor allows researchers to determine the effects of genetic and environmental factors on social interaction, while controlling for potential confounding factors. Diverse factors such as climbing ability, time of day, sex, and number of flies, can modify social spacing of flies. We thus propose a series of experimental controls to mitigate these confounding effects. This assay can be used for at least two purposes. First, researchers can determine how their favorite environmental shift (such as isolation, temperature, stress or toxins) will impact social spacing (1,2). Second, researchers can dissect the genetic and neural underpinnings of this basic form of social behavior (1,3). Specifically, we used it as a diagnostic tool to study the role of orthologous genes thought to be involved in social behavior in other organisms, such as candidate genes for autism in humans (4).

Dietary approaches to stop hypertension diet and obesity: A cross-sectional study of Iranian children and adolescents.

PubMed

Golpour-Hamedani, Sahar; Mohammadifard, Noushin; Khosravi, Alireza; Feizi, Awat; Safavi, Sayyed Morteza

2017-01-01

Few studies have investigated the effects of dietary approaches to stop hypertension (DASH) diet on obesity in children. The present study was conducted to examine adherence to the DASH diet in relation to obesity in children and adolescents, Isfahan, Iran. A cross-sectional study was carried out among 456 children aged 11-18 years who were selected by random cluster sampling method. Dietary intakes were assessed using a validated Food Frequency Questionnaire (FFQ). The DASH score was constructed based on food items emphasized or minimized in the DASH diet. Anthropometric measurements were conducted based on standard protocols. General and abdominal obesity were defined based on body mass index ≥ 95th percentiles and waist: height ratio of more than 0.5, respectively. Higher adherence to DASH diet was inversely associated with general obesity (odds ratioT1 vs. T3 3.34, 95% confidence interval 1.28-8.75); however, after controlling for confounding factors, this association disappeared. Furthermore, higher adherence to DASH diet was negatively associated with central obesity in children, but the relation was not statistically significant. We concluded that there was an inverse nonsignificant association between adherence to DASH diet and general obesity indices after adjustment for potential confounders. Further, well-designed randomized clinical trial studies are suggested to find out the effect of DASH diet on obesity obviously.

Environmental influence of problematic social relationships on adolescents' daily cortisol secretion: a monozygotic twin-difference study.

PubMed

Brendgen, M; Ouellet-Morin, I; Lupien, S J; Vitaro, F; Dionne, G; Boivin, M

2017-02-01

This study investigated the potential environmental effects of peer victimization and the quality of relationships with parents and friends on diurnal cortisol secretion in mid-adolescence. This study used the monozygotic (MZ) twin-difference design to control for genetic effects and thus estimate the unique environmental influences on diurnal cortisol. Participants were 136 MZ twin pairs (74 female pairs) for whom cortisol was assessed four times per day over four collection days grouped in a 2-week period in grade 8 (mean age = 14.07 years). Participants also provided self-reports of peer victimization from grade 4 to grade 8 and of the relationship quality with the mother, father and best friend in grade 8. The expected pattern of diurnal cortisol secretion was observed, with high levels at awakening followed by an increase 30 min later and a progressive decrease subsequently. Controlling for a host of confounders, only within-twin pair differences in peer victimization and a problematic relationship with the mother were significantly linked to twin differences in diurnal cortisol secretion. Specifically, whereas a more problematic mother-child relationship was associated with morning cortisol secretion, peer victimization was linked to cortisol secretion later in the day (diurnal slope). Controlling for genetic influences and other confounders, stressful relationships with peers and the mother exert unique and time-specific environmental influences on the pattern of diurnal cortisol secretion in mid-adolescence.

Contributions of social context to blood pressure: findings from a multilevel analysis of social capital and systolic blood pressure.

PubMed

Hamano, Tsuyoshi; Fujisawa, Yoshikazu; Yamasaki, Masayuki; Ito, Katsuhisa; Nabika, Toru; Shiwaku, Kuninori

2011-06-01

In recent years, few studies have quantified the effect of residential context on blood pressure. Although these studies have emphasized the importance of socioeconomic influences such as education or poverty levels, the association between the features of social structure such as social capital and blood pressure remain unclear. Therefore, we investigated whether social capital was associated with systolic blood pressure after controlling for individual potential confounders. We analyzed data from the Shimane Study conducted from 2006 to 2008 in rural mountainous regions of Japan. After excluding the missing data and data of participants taking hypertension medication, we conducted a multilevel analysis of the data for 335 individuals nested within 30 postcode sectors. Systolic blood pressure increased with increasing age and body mass index. We also found that a higher systolic blood pressure was observed among smokers and those taking medication for diabetes. Regarding the contextual effects of social capital, systolic blood pressure increased with an increasing proportion of lack of fairness, after adjustment for individual confounders. To the best of our knowledge, this study is the first to investigate the association between social capital and systolic blood pressure by using a multilevel methodological framework. Surprisingly, we found that lack of fairness had a strong effect on systolic blood pressure. However, we could not find any significant associations between other items of social capital and systolic blood pressure. Further studies are needed to clarify the mechanism by which lack of fairness may have an effect on systolic blood pressure.