Using propensity scores to estimate the effects of insecticides on stream invertebrates from observational data

USGS Publications Warehouse

Lester L. Yuan,; Amina I. Pollard,; Carlisle, Daren M.

2009-01-01

Analyses of observational data can provide insights into relationships between environmental conditions and biological responses across a broader range of natural conditions than experimental studies, potentially complementing insights gained from experiments. However, observational data must be analyzed carefully to minimize the likelihood that confounding variables bias observed relationships. Propensity scores provide a robust approach for controlling for the effects of measured confounding variables when analyzing observational data. Here, we use propensity scores to estimate changes in mean invertebrate taxon richness in streams that have experienced insecticide concentrations that exceed aquatic life use benchmark concentrations. A simple comparison of richness in sites exposed to elevated insecticides with those that were not exposed suggests that exposed sites had on average 6.8 fewer taxa compared to unexposed sites. The presence of potential confounding variables makes it difficult to assert a causal relationship from this simple comparison. After controlling for confounding factors using propensity scores, the difference in richness between exposed and unexposed sites was reduced to 4.1 taxa, a difference that was still statistically significant. Because the propensity score analysis controlled for the effects of a wide variety of possible confounding variables, we infer that the change in richness observed in the propensity score analysis was likely caused by insecticide exposure.

Using propensity scores to estimate the effects of insecticides on stream invertebrates from observational data

USGS Publications Warehouse

Yuan, L.L.; Pollard, A.I.; Carlisle, D.M.

2009-01-01

Analyses of observational data can provide insights into relationships between environmental conditions and biological responses across a broader range of natural conditions than experimental studies, potentially complementing insights gained from experiments. However, observational data must be analyzed carefully to minimize the likelihood that confounding variables bias observed relationships. Propensity scores provide a robust approach for controlling for the effects of measured confounding variables when analyzing observational data. Here, we use propensity scores to estimate changes in mean invertebrate taxon richness in streams that have experienced insecticide concentrations that exceed aquatic life use benchmark concentrations. A simple comparison of richness in sites exposed to elevated insecticides with those that were not exposed suggests that exposed sites had on average 6.8 fewer taxa compared to unexposed sites. The presence of potential confounding variables makes it difficult to assert a causal relationship from this simple comparison. After controlling for confounding factors using propensity scores, the difference in richness between exposed and unexposed sites was reduced to 4.1 taxa, a difference that was still statistically significant. Because the propensity score analysis controlled for the effects of a wide variety of possible confounding variables, we infer that the change in richness observed in the propensity score analysis was likely caused by insecticide exposure. ?? 2009 SETAC.

Implementing the undergraduate mini-CEX: a tailored approach at Southampton University.

PubMed

Hill, Faith; Kendall, Kathleen; Galbraith, Kevin; Crossley, Jim

2009-04-01

The mini-clinical evaluation exercise (mini-CEX) is widely used in the UK to assess clinical competence, but there is little evidence regarding its implementation in the undergraduate setting. This study aimed to estimate the validity and reliability of the undergraduate mini-CEX and discuss the challenges involved in its implementation. A total of 3499 mini-CEX forms were completed. Validity was assessed by estimating associations between mini-CEX score and a number of external variables, examining the internal structure of the instrument, checking competency domain response rates and profiles against expectations, and by qualitative evaluation of stakeholder interviews. Reliability was evaluated by overall reliability coefficient (R), estimation of the standard error of measurement (SEM), and from stakeholders' perceptions. Variance component analysis examined the contribution of relevant factors to students' scores. Validity was threatened by various confounding variables, including: examiner status; case complexity; attachment specialty; patient gender, and case focus. Factor analysis suggested that competency domains reflect a single latent variable. Maximum reliability can be achieved by aggregating scores over 15 encounters (R = 0.73; 95% confidence interval [CI] +/- 0.28 based on a 6-point assessment scale). Examiner stringency contributed 29% of score variation and student attachment aptitude 13%. Stakeholder interviews revealed staff development needs but the majority perceived the mini-CEX as more reliable and valid than the previous long case. The mini-CEX has good overall utility for assessing aspects of the clinical encounter in an undergraduate setting. Strengths include fidelity, wide sampling, perceived validity, and formative observation and feedback. Reliability is limited by variable examiner stringency, and validity by confounding variables, but these should be viewed within the context of overall assessment strategies.

Nutritional status and the influence of TV consumption on female body size ideals in populations recently exposed to the media.

PubMed

Jucker, Jean-Luc; Thornborrow, Tracey; Beierholm, Ulrik; Burt, D Michael; Barton, Robert A; Evans, Elizabeth H; Jamieson, Mark A; Tovée, Martin J; Boothroyd, Lynda G

2017-08-16

Television consumption influences perceptions of attractive female body size. However, cross-cultural research examining media influence on body ideals is typically confounded by differences in the availability of reliable and diverse foodstuffs. 112 participants were recruited from 3 Nicaraguan villages that differed in television consumption and nutritional status, such that the contribution of both factors could be revealed. Participants completed a female figure preference task, reported their television consumption, and responded to several measures assessing nutritional status. Communities with higher television consumption and/or higher nutritional status preferred thinner female bodies than communities with lower television consumption and/or lower nutritional status. Bayesian mixed models estimated the plausible range of effects for television consumption, nutritional status, and other relevant variables on individual preferences. The model explained all meaningful differences between our low-nutrition villages, and television consumption, after sex, was the most likely of these predictors to contribute to variation in preferences (probability mass >95% when modelling only variables with zero-order associations with preferences, but only 90% when modelling all possible predictors). In contrast, we found no likely link with nutritional status. We thus found evidence that where media access and nutritional status are confounded, media is the more likely predictor of body ideals.

Integrated presentation of ecological risk from multiple stressors

NASA Astrophysics Data System (ADS)

Goussen, Benoit; Price, Oliver R.; Rendal, Cecilie; Ashauer, Roman

2016-10-01

Current environmental risk assessments (ERA) do not account explicitly for ecological factors (e.g. species composition, temperature or food availability) and multiple stressors. Assessing mixtures of chemical and ecological stressors is needed as well as accounting for variability in environmental conditions and uncertainty of data and models. Here we propose a novel probabilistic ERA framework to overcome these limitations, which focusses on visualising assessment outcomes by construct-ing and interpreting prevalence plots as a quantitative prediction of risk. Key components include environmental scenarios that integrate exposure and ecology, and ecological modelling of relevant endpoints to assess the effect of a combination of stressors. Our illustrative results demonstrate the importance of regional differences in environmental conditions and the confounding interactions of stressors. Using this framework and prevalence plots provides a risk-based approach that combines risk assessment and risk management in a meaningful way and presents a truly mechanistic alternative to the threshold approach. Even whilst research continues to improve the underlying models and data, regulators and decision makers can already use the framework and prevalence plots. The integration of multiple stressors, environmental conditions and variability makes ERA more relevant and realistic.

Integrated presentation of ecological risk from multiple stressors.

PubMed

Goussen, Benoit; Price, Oliver R; Rendal, Cecilie; Ashauer, Roman

2016-10-26

Current environmental risk assessments (ERA) do not account explicitly for ecological factors (e.g. species composition, temperature or food availability) and multiple stressors. Assessing mixtures of chemical and ecological stressors is needed as well as accounting for variability in environmental conditions and uncertainty of data and models. Here we propose a novel probabilistic ERA framework to overcome these limitations, which focusses on visualising assessment outcomes by construct-ing and interpreting prevalence plots as a quantitative prediction of risk. Key components include environmental scenarios that integrate exposure and ecology, and ecological modelling of relevant endpoints to assess the effect of a combination of stressors. Our illustrative results demonstrate the importance of regional differences in environmental conditions and the confounding interactions of stressors. Using this framework and prevalence plots provides a risk-based approach that combines risk assessment and risk management in a meaningful way and presents a truly mechanistic alternative to the threshold approach. Even whilst research continues to improve the underlying models and data, regulators and decision makers can already use the framework and prevalence plots. The integration of multiple stressors, environmental conditions and variability makes ERA more relevant and realistic.

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

Evaluation of uncontrolled confounding in studies of environmental exposures and neurobehavioral testing in children.

PubMed

Mink, Pamela J; Goodman, Michael; Barraj, Leila M; Imrey, Harriet; Kelsh, Michael A; Yager, Janice

2004-07-01

Neurobehavioral tests are commonly used in studies of children exposed to low-level environmental concentrations of compounds known to be neurotoxic at higher levels. However, uncontrolled or incomplete control for confounding makes interpretation of results problematic because effects of confounders are often stronger than the effects of primary interest. We examined a priori the potential impact of confounding in a hypothetical study evaluating the association of a potentially neurotoxic environmental exposure with neurobehavioral function in children. We used 2 outcome measures: the Bayley Scales of Infant Development Mental Development Index and the Stanford-Binet Intelligence Scale Composite Score. We selected 3 potential confounders: maternal intelligence, home environment, and socioeconomic status as measured by years of parental education. We conducted 3 sets of analyses measuring the effect of each of the 3 confounding factors alone, 2 confounders acting simultaneously, and all 3 confounders acting simultaneously. Relatively small differences (0.5 standard deviations) in confounding variables between "exposed" and "unexposed" groups, if unmeasured and unaccounted for in the analysis, could produce spurious differences in cognitive test scores. The magnitude of this difference (3-10 points) has been suggested to have a meaningful impact in populations. The method of measuring confounders (eg, maternal intelligence) could also substantially affect the results. It is important to carefully consider the impact of potential confounders during the planning stages of an observational study. Study-to-study differences in neurobehavioral outcomes with similar environmental exposures could be partially explained by differences in the adjustment for confounding variables. Copyright 2004 Lippincott Williams and Wilkins

Investigating the relationship between neighborhood poverty and mortality risk: A marginal structural modeling approach

PubMed Central

Do, D. Phuong; Wang, Lu; Elliott, Michael R.

2013-01-01

Extant observational studies generally support the existence of a link between neighborhood context and health. However, estimating the causal impact of neighborhood effects from observational data has proven to be a challenge. Omission of relevant factors may lead to overestimating the effects of neighborhoods on health while inclusion of time-varying confounders that may also be mediators (e.g., income, labor force status) may lead to underestimation. Using longitudinal data from the 1990 to 2007 years of the Panel Study of Income Dynamics, this study investigates the link between neighborhood poverty and overall mortality risk. A marginal structural modeling strategy is employed to appropriately adjust for simultaneous mediating and confounding factors. To address the issue of possible upward bias from the omission of key variables, sensitivity analysis to assess the robustness of results against unobserved confounding is conducted. We examine two continuous measures of neighborhood poverty – single-point and a running average. Both were specified as piece-wise linear splines with a knot at 20 percent. We found no evidence from the traditional naïve strategy that neighborhood context influences mortality risk. In contrast, for both the single-point and running average neighborhood poverty specifications, the marginal structural model estimates indicated a statistically significant increase in mortality risk with increasing neighborhood poverty above the 20 percent threshold. For example, below 20 percent neighborhood poverty, no association was found. However, after the 20 percent poverty threshold is reached, each 10 percentage point increase in running average neighborhood poverty was found to increase the odds for mortality by 89 percent [95% CI = 1.22, 2.91]. Sensitivity analysis indicated that estimates were moderately robust to omitted variable bias. PMID:23849239

Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

PubMed

Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

2016-06-01

Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results.

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.

Implementation of Instrumental Variable Bounds for Data Missing Not at Random.

PubMed

Marden, Jessica R; Wang, Linbo; Tchetgen, Eric J Tchetgen; Walter, Stefan; Glymour, M Maria; Wirth, Kathleen E

2018-05-01

Instrumental variables are routinely used to recover a consistent estimator of an exposure causal effect in the presence of unmeasured confounding. Instrumental variable approaches to account for nonignorable missing data also exist but are less familiar to epidemiologists. Like instrumental variables for exposure causal effects, instrumental variables for missing data rely on exclusion restriction and instrumental variable relevance assumptions. Yet these two conditions alone are insufficient for point identification. For estimation, researchers have invoked a third assumption, typically involving fairly restrictive parametric constraints. Inferences can be sensitive to these parametric assumptions, which are typically not empirically testable. The purpose of our article is to discuss another approach for leveraging a valid instrumental variable. Although the approach is insufficient for nonparametric identification, it can nonetheless provide informative inferences about the presence, direction, and magnitude of selection bias, without invoking a third untestable parametric assumption. An important contribution of this article is an Excel spreadsheet tool that can be used to obtain empirical evidence of selection bias and calculate bounds and corresponding Bayesian 95% credible intervals for a nonidentifiable population proportion. For illustrative purposes, we used the spreadsheet tool to analyze HIV prevalence data collected by the 2007 Zambia Demographic and Health Survey (DHS).

Estimating Causal Effects with Ancestral Graph Markov Models

PubMed Central

Malinsky, Daniel; Spirtes, Peter

2017-01-01

We present an algorithm for estimating bounds on causal effects from observational data which combines graphical model search with simple linear regression. We assume that the underlying system can be represented by a linear structural equation model with no feedback, and we allow for the possibility of latent variables. Under assumptions standard in the causal search literature, we use conditional independence constraints to search for an equivalence class of ancestral graphs. Then, for each model in the equivalence class, we perform the appropriate regression (using causal structure information to determine which covariates to include in the regression) to estimate a set of possible causal effects. Our approach is based on the “IDA” procedure of Maathuis et al. (2009), which assumes that all relevant variables have been measured (i.e., no unmeasured confounders). We generalize their work by relaxing this assumption, which is often violated in applied contexts. We validate the performance of our algorithm on simulated data and demonstrate improved precision over IDA when latent variables are present. PMID:28217244

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.

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.

Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort

PubMed Central

Green, Emma; Shafto, Meredith A.; Matthews, Fiona E.; White, Simon R.

2015-01-01

This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups. PMID:26690191

Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort.

PubMed

Green, Emma; Shafto, Meredith A; Matthews, Fiona E; White, Simon R

2015-12-07

This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups.

Cross-reactivity and masqueraders in seafood reactions.

PubMed

Banks, Taylor A; Gada, Satyen M

2013-01-01

Confounding variables play a significant role in many adverse seafood reactions and a clear understanding of these factors is important in properly characterizing reactions associated with potential masqueraders and mimics. Although the medical literature is replete with reviews of seafood hypersensitivity and reports of cross-reactive and newly characterized allergens, there has not been a recent effort to provide an updated overview of the several processes that may lead clinicians to draw incorrect conclusions in evaluating reported reactions to seafood. Ranging from seafood intoxications to other nonallergic or complex seafood reactions, these events can easily be misconstrued as representing a seafood IgE-mediated allergy. Among these are the more familiar topics of cross-reactivity and scombroid intoxication, and those with a still evolving understanding such as ciguatera fish poisoning and Anisakis reactions. This article seeks to provide an accessible but comprehensive summary of the relevant information surrounding these confounders in assessing adverse reactions to seafood. Such knowledge may be instrumental in unraveling complex or otherwise unclear presentations and aid clinicians in accurately evaluating and managing patients with reported seafood reactions.

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).

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.

Integrated presentation of ecological risk from multiple stressors

PubMed Central

Goussen, Benoit; Price, Oliver R.; Rendal, Cecilie; Ashauer, Roman

2016-01-01

Current environmental risk assessments (ERA) do not account explicitly for ecological factors (e.g. species composition, temperature or food availability) and multiple stressors. Assessing mixtures of chemical and ecological stressors is needed as well as accounting for variability in environmental conditions and uncertainty of data and models. Here we propose a novel probabilistic ERA framework to overcome these limitations, which focusses on visualising assessment outcomes by construct-ing and interpreting prevalence plots as a quantitative prediction of risk. Key components include environmental scenarios that integrate exposure and ecology, and ecological modelling of relevant endpoints to assess the effect of a combination of stressors. Our illustrative results demonstrate the importance of regional differences in environmental conditions and the confounding interactions of stressors. Using this framework and prevalence plots provides a risk-based approach that combines risk assessment and risk management in a meaningful way and presents a truly mechanistic alternative to the threshold approach. Even whilst research continues to improve the underlying models and data, regulators and decision makers can already use the framework and prevalence plots. The integration of multiple stressors, environmental conditions and variability makes ERA more relevant and realistic. PMID:27782171

Distinguishing prostate cancer from benign confounders via a cascaded classifier on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Litjens, G. J. S.; Elliott, R.; Shih, N.; Feldman, M.; Barentsz, J. O.; Hulsbergen-van de Kaa, C. A.; Kovacs, I.; Huisman, H. J.; Madabhushi, A.

2014-03-01

Learning how to separate benign confounders from prostate cancer is important because the imaging characteristics of these confounders are poorly understood. Furthermore, the typical representations of the MRI parameters might not be enough to allow discrimination. The diagnostic uncertainty this causes leads to a lower diagnostic accuracy. In this paper a new cascaded classifier is introduced to separate prostate cancer and benign confounders on MRI in conjunction with specific computer-extracted features to distinguish each of the benign classes (benign prostatic hyperplasia (BPH), inflammation, atrophy or prostatic intra-epithelial neoplasia (PIN). In this study we tried to (1) calculate different mathematical representations of the MRI parameters which more clearly express subtle differences between different classes, (2) learn which of the MRI image features will allow to distinguish specific benign confounders from prostate cancer, and (2) find the combination of computer-extracted MRI features to best discriminate cancer from the confounding classes using a cascaded classifier. One of the most important requirements for identifying MRI signatures for adenocarcinoma, BPH, atrophy, inflammation, and PIN is accurate mapping of the location and spatial extent of the confounder and cancer categories from ex vivo histopathology to MRI. Towards this end we employed an annotated prostatectomy data set of 31 patients, all of whom underwent a multi-parametric 3 Tesla MRI prior to radical prostatectomy. The prostatectomy slides were carefully co-registered to the corresponding MRI slices using an elastic registration technique. We extracted texture features from the T2-weighted imaging, pharmacokinetic features from the dynamic contrast enhanced imaging and diffusion features from the diffusion-weighted imaging for each of the confounder classes and prostate cancer. These features were selected because they form the mainstay of clinical diagnosis. Relevant features for each of the classes were selected using maximum relevance minimum redundancy feature selection, allowing us to perform classifier independent feature selection. The selected features were then incorporated in a cascading classifier, which can focus on easier sub-tasks at each stage, leaving the more difficult classification tasks for later stages. Results show that distinct features are relevant for each of the benign classes, for example the fraction of extra-vascular, extra-cellular space in a voxel is a clear discriminator for inflammation. Furthermore, the cascaded classifier outperforms both multi-class and one-shot classifiers in overall accuracy for discriminating confounders from cancer: 0.76 versus 0.71 and 0.62.

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.

Bayesian effect estimation accounting for adjustment uncertainty.

PubMed

Wang, Chi; Parmigiani, Giovanni; Dominici, Francesca

2012-09-01

Model-based estimation of the effect of an exposure on an outcome is generally sensitive to the choice of which confounding factors are included in the model. We propose a new approach, which we call Bayesian adjustment for confounding (BAC), to estimate the effect of an exposure of interest on the outcome, while accounting for the uncertainty in the choice of confounders. Our approach is based on specifying two models: (1) the outcome as a function of the exposure and the potential confounders (the outcome model); and (2) the exposure as a function of the potential confounders (the exposure model). We consider Bayesian variable selection on both models and link the two by introducing a dependence parameter, ω, denoting the prior odds of including a predictor in the outcome model, given that the same predictor is in the exposure model. In the absence of dependence (ω= 1), BAC reduces to traditional Bayesian model averaging (BMA). In simulation studies, we show that BAC, with ω > 1, estimates the exposure effect with smaller bias than traditional BMA, and improved coverage. We, then, compare BAC, a recent approach of Crainiceanu, Dominici, and Parmigiani (2008, Biometrika 95, 635-651), and traditional BMA in a time series data set of hospital admissions, air pollution levels, and weather variables in Nassau, NY for the period 1999-2005. Using each approach, we estimate the short-term effects of on emergency admissions for cardiovascular diseases, accounting for confounding. This application illustrates the potentially significant pitfalls of misusing variable selection methods in the context of adjustment uncertainty. © 2012, The International Biometric Society.

Exposure to Online Alcohol Marketing and Adolescents' Drinking: A Cross-sectional Study in Four European Countries.

PubMed

de Bruijn, Avalon; Engels, Rutger; Anderson, Peter; Bujalski, Michal; Gosselt, Jordy; Schreckenberg, Dirk; Wohtge, Jördis; de Leeuw, Rebecca

2016-09-01

The Internet is the leading medium among European adolescents in contemporary times; even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in four European countries. A total of 9038 students with a mean age of 14.05 (SD 0.82) participated in a school-based survey in Germany, Italy, the Netherlands and Poland. Logistic regression analyses of cross-sectional cross-country survey data were undertaken. Exposure to online alcohol marketing, televised alcohol advertising and ownership of alcohol-branded items was estimated to be controlled for relevant confounders. Onset of drinking and binge drinking in the past 30 days were included in the study as outcome variables. Adjusted for relevant confounders, higher exposure to (online) alcohol marketing exposure was found to be related to the odds of starting to drink (p < 0.001) and the odds of binge drinking in the past 30 days (p < 0.001). This effect was found to be consistent in all four countries. Active engagement with online alcohol marketing was found to interact more strongly with drinking outcomes than passive exposure to online alcohol marketing. Youngsters in the four European countries report frequent exposure to online alcohol marketing. The association between this exposure and adolescents' drinking was robust and seems consistent across national contexts. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis.

PubMed

Jin, Huifeng; Cheng, Haojie; Chen, Wei; Sheng, Xiaoming; Levy, Mark A; Brown, Mark J; Tian, Junqiang

2018-05-01

The single nucleotide polymorphism of the gene 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. We hypothesized that variability in this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers, confounders, or both, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates. We systematically extracted from published studies the data on tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting metadata set was first used to analyze the covariates' modifying effect by meta-regression and other statistical means. Subsequently, we controlled for this modifying effect by genotype-stratifying tHcy data and analyzed the variability in the risk resulting from the confounding of covariates. The data set contains data on 36 rs1801133 covariates that were collected from 114,799 participants and 256 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification as well as confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner. We showed an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public, who increasingly receive genetic data from commercial services without interpretation of its clinical relevance. This study was registered at Research Registry with the registration number reviewregistry328.

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

Are Stage of Change constructs relevant for subjective oral health in a vulnerable population?

PubMed

Jamieson, L M; Parker, E J; Broughton, J; Lawrence, H P; Armfield, J M

2015-06-01

Stage of Change constructs may be proxy markers of psychosocial health which, in turn, are related to oral health. To determine if Stage of Change constructs were associated with subjective oral health in a population at heightened risk of dental disease. Stage of Change constructs were developed from a validated 18-item scale and categorised into 'Pre-contemplative', 'Contemplative' and 'Active'. A convenience sample of 446 Australian non-Aboriginal women pregnant by an Aboriginal male (age range 14-43 years) provided data to evaluate the outcome variables (self-rated oral health and oral health impairment), the Stage of Change constructs and socio-demographic, behavioural and access-related factors. Factors significant at the p < 0.05 level in bivariate analysis were entered into prevalence regression models. Approximately 54% of participants had fair/poor self-rated oral health and 34% had oral health impairment. Around 12% were 'Pre-contemplative', 46% 'Contemplative' and 42% 'Active'. Being either 'pre-contemplative' or 'contemplative' was associated with poor self-rated oral health after adjusting for socio-demographic factors. 'Pre-contemplative' ceased being significant after adjusting for dentate status and dental behaviour. 'Pre-contemplative' remained significant when adjusting for dental cost, but not 'Contemplative'. The Stages of Change constructs ceased being associated with self-rated oral health after adjusting for all confounders. Only 'Contemplative' (reference: 'Active') was a risk indicator in the null model for oral health impairment which persisted after adding dentate status, dental behaviour and dental cost variables, but not socio-demographics. When adjusting for all confounders, 'Contemplative' was not a risk indicator for oral health impairment. Both the 'Pre-contemplative' and 'Contemplative' Stage of Change constructs were associated with poor self-rated oral health and oral health impairment after adjusting for some, but not all, covariates. When considered as a proxy marker of psychosocial health, Stage of Change constructs may have some relevance for subjective oral health.

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.

Instrumental variables as bias amplifiers with general outcome and confounding.

PubMed

Ding, P; VanderWeele, T J; Robins, J M

2017-06-01

Drawing causal inference with observational studies is the central pillar of many disciplines. One sufficient condition for identifying the causal effect is that the treatment-outcome relationship is unconfounded conditional on the observed covariates. It is often believed that the more covariates we condition on, the more plausible this unconfoundedness assumption is. This belief has had a huge impact on practical causal inference, suggesting that we should adjust for all pretreatment covariates. However, when there is unmeasured confounding between the treatment and outcome, estimators adjusting for some pretreatment covariate might have greater bias than estimators without adjusting for this covariate. This kind of covariate is called a bias amplifier, and includes instrumental variables that are independent of the confounder, and affect the outcome only through the treatment. Previously, theoretical results for this phenomenon have been established only for linear models. We fill in this gap in the literature by providing a general theory, showing that this phenomenon happens under a wide class of models satisfying certain monotonicity assumptions. We further show that when the treatment follows an additive or multiplicative model conditional on the instrumental variable and the confounder, these monotonicity assumptions can be interpreted as the signs of the arrows of the causal diagrams.

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.

Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study.

PubMed

Colle, Romain; Segawa, Tomoyuki; Chupin, Marie; Tran Dong, Minh Ngoc Thien Kim; Hardy, Patrick; Falissard, Bruno; Colliot, Olivier; Ducreux, Denis; Corruble, Emmanuelle

2017-02-15

Three studies assessed the association of early life adversity (ELA) and hippocampal volumes in depressed patients, of which one was negative and the two others did not control for several potential confounding variables. Since the association of ELA and hippocampal volumes differ in male and female healthy volunteers, we investigated the association of ELA and hippocampal volumes in depressed patients, while focusing specifically on sex and controlling for several relevant socio-demographic and clinical variables. Sixty-three depressed in-patients treated in a psychiatric setting, with a current Major Depressive Episode (MDE) and a Major Depressive Disorder (MDD) were included and assessed for ELA. Hippocampal volumes were measured with brain magnetic resonance imaging (MRI) and automatic segmentation. They were compared between patients with (n = 28) or without (n = 35) ELA. After bivariate analyses, multivariate regression analyses tested the interaction of sex and ELA on hippocampal volume and were adjusted for several potential confounding variables. The subgroups of men (n = 26) and women (n = 37) were assessed separately. Patients with ELA had a smaller hippocampus than those without ELA (4.65 (±1.11) cm 3 versus 5.25 (±1.01) cm 3 ), bivariate: p = 0.03, multivariate: HR = 0.40, 95%CI [0.23;0.71], p = 0.002), independently from other factors. This association was found in men (4.43 (±1.22) versus 5.67 (±0.77) cm 3 ), bivariate: p = 0.006, multivariate HR = 0.23, 95%CI [0.06;0.82], p = 0.03) but not in women. ELA is associated with a smaller hippocampus in male but not female depressed in-patients. The reasons for this association should be investigated in further studies.

Detection rates of geckos in visual surveys: Turning confounding variables into useful knowledge

USGS Publications Warehouse

Lardner, Bjorn; Rodda, Gordon H.; Yackel Adams, Amy A.; Savidge, Julie A.; Reed, Robert N.

2016-01-01

Transect surveys without some means of estimating detection probabilities generate population size indices prone to bias because survey conditions differ in time and space. Knowing what causes such bias can help guide the collection of relevant survey covariates, correct the survey data, anticipate situations where bias might be unacceptably large, and elucidate the ecology of target species. We used negative binomial regression to evaluate confounding variables for gecko (primarily Hemidactylus frenatus and Lepidodactylus lugubris) counts on 220-m-long transects surveyed at night, primarily for snakes, on 9,475 occasions. Searchers differed in gecko detection rates by up to a factor of six. The worst and best headlamps differed by a factor of at least two. Strong winds had a negative effect potentially as large as those of searchers or headlamps. More geckos were seen during wet weather conditions, but the effect size was small. Compared with a detection nadir during waxing gibbous (nearly full) moons above the horizon, we saw 28% more geckos during waning crescent moons below the horizon. A sine function suggested that we saw 24% more geckos at the end of the wet season than at the end of the dry season. Fluctuations on a longer timescale also were verified. Disturbingly, corrected data exhibited strong short-term fluctuations that covariates apparently failed to capture. Although some biases can be addressed with measured covariates, others will be difficult to eliminate as a significant source of error in longterm monitoring programs.

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.

Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study.

PubMed

Gallagher, Patience J; Castro, Victor; Fava, Maurizio; Weilburg, Jeffrey B; Murphy, Shawn N; Gainer, Vivian S; Churchill, Susanne E; Kohane, Isaac S; Iosifescu, Dan V; Smoller, Jordan W; Perlis, Roy H

2012-10-01

OBJECTIVE It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system. METHOD Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed. RESULTS NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21-2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables. CONCLUSIONS These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding.

Children's concepts of physical illness: a review and critique of the cognitive-developmental literature.

PubMed

Burbach, D J; Peterson, L

1986-01-01

Cognitive-developmental studies relevant to children's concepts of physical illness are reviewed and critiqued. Although numerous methodological weaknesses make firm conclusions difficult, most data appear to suggest that children's concepts of illness do evolve in a systematic and predictable sequence consistent with Piaget's theory of cognitive development. Methodological weaknesses identified include poor description of samples, assessment instruments, and procedures; lack of control over potential observer bias, expectancy effects, and other confounding variables; and minimal attention to reliability and validity issues. Increased methodological rigor and a further explication of the specific and unique ways in which children's concepts of illness develop over the course of cognitive development could substantially increase the value of these studies for professionals in pediatric health care settings.

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

Incorporating microbiota data into epidemiologic models: examples from vaginal microbiota research.

PubMed

van de Wijgert, Janneke H; Jespers, Vicky

2016-05-01

Next generation sequencing and quantitative polymerase chain reaction technologies are now widely available, and research incorporating these methods is growing exponentially. In the vaginal microbiota (VMB) field, most research to date has been descriptive. The purpose of this article is to provide an overview of different ways in which next generation sequencing and quantitative polymerase chain reaction data can be used to answer clinical epidemiologic research questions using examples from VMB research. We reviewed relevant methodological literature and VMB articles (published between 2008 and 2015) that incorporated these methodologies. VMB data have been analyzed using ecologic methods, methods that compare the presence or relative abundance of individual taxa or community compositions between different groups of women or sampling time points, and methods that first reduce the complexity of the data into a few variables followed by the incorporation of these variables into traditional biostatistical models. To make future VMB research more clinically relevant (such as studying associations between VMB compositions and clinical outcomes and the effects of interventions on the VMB), it is important that these methods are integrated with rigorous epidemiologic methods (such as appropriate study designs, sampling strategies, and adjustment for confounding). Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Controlling for confounding variables in MS-omics protocol: why modularity matters.

PubMed

Smith, Rob; Ventura, Dan; Prince, John T

2014-09-01

As the field of bioinformatics research continues to grow, more and more novel techniques are proposed to meet new challenges and improvements upon solutions to long-standing problems. These include data processing techniques and wet lab protocol techniques. Although the literature is consistently thorough in experimental detail and variable-controlling rigor for wet lab protocol techniques, bioinformatics techniques tend to be less described and less controlled. As the validation or rejection of hypotheses rests on the experiment's ability to isolate and measure a variable of interest, we urge the importance of reducing confounding variables in bioinformatics techniques during mass spectrometry experimentation. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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.

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.

Overcoming ecologic bias using the two-phase study design.

PubMed

Wakefield, Jon; Haneuse, Sebastien J-P A

2008-04-15

Ecologic (aggregate) data are widely available and widely utilized in epidemiologic studies. However, ecologic bias, which arises because aggregate data cannot characterize within-group variability in exposure and confounder variables, can only be removed by supplementing ecologic data with individual-level data. Here the authors describe the two-phase study design as a framework for achieving this objective. In phase 1, outcomes are stratified by any combination of area, confounders, and error-prone (or discretized) versions of exposures of interest. Phase 2 data, sampled within each phase 1 stratum, provide accurate measures of exposure and possibly of additional confounders. The phase 1 aggregate-level data provide a high level of statistical power and a cross-classification by which individuals may be efficiently sampled in phase 2. The phase 2 individual-level data then provide a control for ecologic bias by characterizing the within-area variability in exposures and confounders. In this paper, the authors illustrate the two-phase study design by estimating the association between infant mortality and birth weight in several regions of North Carolina for 2000-2004, controlling for gender and race. This example shows that the two-phase design removes ecologic bias and produces gains in efficiency over the use of case-control data alone. The authors discuss the advantages and disadvantages of the approach.

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.

Animal Models in Genomic Research: Techniques, Applications, and Roles for Nurses

PubMed Central

Osier, Nicole D.; Pham, Lan; Savarese, Amanda; Sayles, Kendra

2016-01-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. PMID:27969037

Animal models in genomic research: Techniques, applications, and roles for nurses.

PubMed

Osier, Nicole D; Pham, Lan; Savarese, Amanda; Sayles, Kendra; Alexander, Sheila A

2016-11-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

Sociodemographic, lifestyle, and psychosocial determinants of hair cortisol in a South London community sample.

PubMed

Fischer, Susanne; Duncko, Roman; Hatch, Stephani L; Papadopoulos, Andrew; Goodwin, Laura; Frissa, Souci; Hotopf, Matthew; Cleare, Anthony J

2017-02-01

Hypothalamic-pituitary-adrenal (HPA) measures are crucial for research into stress and stress-related disorders. Most HPA measures fluctuate depending on diurnal rhythms and state confounders. Hair cortisol concentrations (HCC) are less susceptible to such fluctuations, but less is known about trait-like confounders. Using a community sample, we tested the relationship between HCC and a range of variables including demographic variables, hair treatment, and medication, as well as psychosocial variables, namely childhood trauma, critical life events, and depressive symptoms. Hair samples were collected from 144 individuals from the South East London Community Health (SELCoH) study. Childhood trauma, life events, and depressive symptoms were measured, together with age, sex, ethnicity, relationship status, educational attainment, employment status, occupational social class, hair washing frequency, hair treatments, season reflected in the hair sample, hazardous drinking, smoking, medication intake, and body mass index. Hair samples reflecting the past 3 months were collected and analysed using immunoassays. First, correlations (continuous variables) and simple linear regressions (dichotomous variables) were conducted to identify sociodemographic, hair-related, and lifestyle determinants of HCC. Next, multiple linear regressions were conducted to test the relationship between psychosocial variables and HCC when controlling for the identified confounders. Age (r=-0.17, p=0.050), White British ethnicity (β=-0.19, p=0.023), heat-based treatments (β=-0.22, p=0.010), and winter season (β=-0.18, p=0.024) were associated with lower HCC, whereas summer season (β=0.24, p=0.024), painkillers (β=0.25, p=0.003), anxiolytics/antidepressants (β=0.21, p=0.014), and hormonal contraceptives (β=0.27, p=0.006) were associated with higher HCC. Controlling for these confounders, physical neglect during childhood (β=-0.17, p=0.057), war-related experiences (β=0.20, p=0.027), separation (β=0.18, p=0.054), and being the victim of a serious crime (β=-0.17, p=0.062) were linked with altered HCC. Our findings suggest that variation in HCC occurs according to sociodemographic, hair-related, and lifestyle variables, and that certain associations between stress and altered HCC can only be revealed when accounting for these confounders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solar radiation increases suicide rate after adjusting for other climate factors in South Korea.

PubMed

Jee, Hee-Jung; Cho, Chul-Hyun; Lee, Yu Jin; Choi, Nari; An, Hyonggin; Lee, Heon-Jeong

2017-03-01

Previous studies have indicated that suicide rates have significant seasonal variations. There is seasonal discordance between temperature and solar radiation due to the monsoon season in South Korea. We investigated the seasonality of suicide and assessed its association with climate variables in South Korea. Suicide rates were obtained from the National Statistical Office of South Korea, and climatic data were obtained from the Korea Meteorological Administration for the period of 1992-2010. We conducted analyses using a generalized additive model (GAM). First, we explored the seasonality of suicide and climate variables such as mean temperature, daily temperature range, solar radiation, and relative humidity. Next, we identified confounding climate variables associated with suicide rate. To estimate the adjusted effect of solar radiation on the suicide rate, we investigated the confounding variables using a multivariable GAM. Suicide rate showed seasonality with a pattern similar to that of solar radiation. We found that the suicide rate increased 1.008 times when solar radiation increased by 1 MJ/m 2 after adjusting for other confounding climate factors (P < 0.001). Solar radiation has a significant linear relationship with suicide after adjusting for region, other climate variables, and time trends. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Mismeasurement and the resonance of strong confounders: correlated errors.

PubMed

Marshall, J R; Hastrup, J L; Ross, J S

1999-07-01

Confounding in epidemiology, and the limits of standard methods of control for an imperfectly measured confounder, have been understood for some time. However, most treatments of this problem are based on the assumption that errors of measurement in confounding and confounded variables are independent. This paper considers the situation in which a strong risk factor (confounder) and an inconsequential but suspected risk factor (confounded) are each measured with errors that are correlated; the situation appears especially likely to occur in the field of nutritional epidemiology. Error correlation appears to add little to measurement error as a source of bias in estimating the impact of a strong risk factor: it can add to, diminish, or reverse the bias induced by measurement error in estimating the impact of the inconsequential risk factor. Correlation of measurement errors can add to the difficulty involved in evaluating structures in which confounding and measurement error are present. In its presence, observed correlations among risk factors can be greater than, less than, or even opposite to the true correlations. Interpretation of multivariate epidemiologic structures in which confounding is likely requires evaluation of measurement error structures, including correlations among measurement errors.

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

Role of Body Mass Index and Gestational Weight Gain in Breastfeeding Outcomes

PubMed Central

Schaefer, Eric W.; Beiler, Jessica S.; Paul, Ian M.

2012-01-01

Abstract Objective This study determined whether high maternal prepregnancy body mass index (BMI) and/or excess gestational weight gain (GWG) is associated with reduced breastfeeding duration and earlier formula supplementation. Study Design A prospective longitudinal cohort of postpartum women (n=718), who were a subset of a larger randomized trial, was followed for 6 months postdelivery. We evaluated the relationship between BMI or BMI/GWG groups and timing of breastfeeding cessation and introduction of formula using Kaplan–Meier curves and log-rank tests. Then, we used multivariable Cox proportional hazards models to evaluate the relationship between BMI and BMI/GWG on these breastfeeding outcomes after controlling for potential confounding variables. Results The expected relationships between high BMI and high BMI/GWG and poor breastfeeding outcomes were observed in Kaplan–Meier curves. However, after adjusting for relevant maternal and infant covariates in the Cox models, the differences became nonsignificant. Prepregnancy BMI category was not statistically associated with breastfeeding duration (p=0.06) or timing of formula introduction (p=0.15). Similarly, BMI and GWG in combination were not associated with duration (p=0.33) or timing of formula introduction (p=0.18). Mothers' intended breastfeeding duration and rating of the importance of breastfeeding remained the only significant modifiable predictors of breastfeeding outcomes in the final models. Conclusions Maternal BMI and GWG were not significantly associated with breastfeeding outcomes after adjusting for confounding variables. Mothers' plans for breastfeeding duration and the importance mothers assign to breastfeeding remain the optimal intervention points for lengthening breastfeeding duration and reducing formula supplementation. PMID:23215909

A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables: A Prospective, Non-US Cross-sectional Study in 292 Patients.

PubMed

Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny

2016-05-01

Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus +  + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the effects of increasing grade level on odds for worse ODI scores remained significant after adjusting for potential confounders. However, effects of age group and aetiology should not be neglected. 3.

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.

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.

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.

[The intelligence quotient and malnutrition. Iron deficiency and the lead concentration as confusing variables].

PubMed

Vega-Franco, L; Mejía, A M; Robles, B; Moreno, L; Pérez, Y

1991-11-01

This study gave us the opportunity to know the roles iron deficiency and the presence of lead in blood play, as confounding variables, in relation to the state of malnutrition and the intellect of those children. A sample of 169 school children were classified according to their state of nutrition, their condition in reference to serum iron and lead concentrations. In addition, their intelligence was evaluated. The results confirmed that those children with lower weights and heights registered lesser points of intelligence; in fact, iron deficiency cancels out the difference in favor of those taller and weighing more. Lead did not contribute as a confounding variable, but more than half of the children showed possible toxic levels of this metal.

Nutritional Risk is Associated with Chronic Musculoskeletal Pain in Community-dwelling Older Persons: The PAINEL Study.

PubMed

Bárbara Pereira Costa, Aline; Andrade Carneiro Machado, Luciana; Marcos Domingues Dias, João; Keller Coelho de Oliveira, Adriana; Ude Viana, Joana; da Silva, Sílvia Lanziotti Azevedo; Gonçalves Pereira Couto, Flávia; Lustosa Torres, Juliana; Mendes, Liliane P; Correa Dias, Rosangela

2016-01-01

Malnutrition is a risk factor for noncommunicable diseases related to ageing, and it can also contribute to musculoskeletal health. This study investigated whether nutritional risk is associated with chronic musculoskeletal pain in community-dwelling older persons. Nutritional risk was assessed by the DETERMINE Checklist. Chronic musculoskeletal pain was defined as the presence of pain in the past six months that did not disappear for at least 30 consecutive days. Multivariate logistic regression including confounding variables was used for the analysis. The sample was comprised of 383 participants (age 75.6 ± SD 6.1); the majority were at moderate-to-high nutritional risk (69%) and approximately one third presented chronic musculoskeletal pain (30%). The nutritional risk score was independently associated with chronic musculoskeletal pain: adding one unit in the risk score produces an 11% increment in the odds of presenting pain (OR 1.109, 95% CI 1.022-1.204). Individuals classified into moderate- or high-risk categories also had substantially higher odds (∼90%) of presenting chronic musculoskeletal pain when compared to those in the low-risk category, although our findings were only marginally significant. This is the first study to demonstrate the association between nutritional risk and chronic musculoskeletal pain above and beyond the contributed effects from relevant confounders.

Gestational diabetes mellitus and risk of type 2 diabetes 10 years after the index pregnancy in Sri Lankan women-A community based retrospective cohort study.

PubMed

Herath, Himali; Herath, Rasika; Wickremasinghe, Rajitha

2017-01-01

Women with a history of gestational diabetes mellitus (GDM) have an increased risk of type 2 diabetes mellitus (T2DM) later in life compared to women with no GDM. This study was aimed to determine the risk of developing T2DM 10 years after GDM in Sri Lankan women. A retrospective cohort study was conducted in the Colombo district, Sri Lanka. 7205 women who delivered a child in 2005 were identified through Public Health Midwives in the field. Women with antenatal records were interviewed and relevant data were extracted from medical records to identify potential participants. One hundred and nineteen women who had GDM and 240 women who did not have GDM were recruited. Current diagnosis of diabetes was based on history, relevant medical records and blood reports within the past 1 year. The mean duration of follow up was 10.9 (SD = 0.35) years in the GDM group and 10.8 (SD = 0.31) years in the non-GDM group. The incidence density of diabetes in the GDM group was 56.3 per 1000 person years compared to 5.4 per 1000 person years in non GDM group giving a rate ratio of 10.42 (95% CI: 6.01-19.12). A woman having GDM in the index pregnancy was 10.6 times more likely to develop diabetes within 10 years compared to women with no GDM after controlling for other confounding variables. Delivering a child after 30 years, being treated with insulin during the pregnancy and delivering a baby weighing more than 3.5 Kg were significant predictors of development of T2DM after controlling for family history of diabetes mellitus (DM), GDM in previous pregnancies, parity and gestational age at delivery. Women with GDM had a 10-fold higher risk of developing T2DM during a 10-year follow up period as compared to women with no GDM after controlling for other confounding variables.

Measurement of testosterone in human sexuality research: methodological considerations.

PubMed

van Anders, Sari M; Goldey, Katherine L; Bell, Sarah N

2014-02-01

Testosterone (T) and other androgens are incorporated into an increasingly wide array of human sexuality research, but there are a number of issues that can affect or confound research outcomes. This review addresses various methodological issues relevant to research design in human studies with T; unaddressed, these issues may introduce unwanted noise, error, or conceptual barriers to interpreting results. Topics covered are (1) social and demographic factors (gender and sex; sexual orientations and sexual diversity; social/familial connections and processes; social location variables), (2) biological rhythms (diurnal variation; seasonality; menstrual cycles; aging and menopause), (3) sample collection, handling, and storage (saliva vs. blood; sialogogues, saliva, and tubes; sampling frequency, timing, and context; shipping samples), (4) health, medical issues, and the body (hormonal contraceptives; medications and nicotine; health conditions and stress; body composition, weight, and exercise), and (5) incorporating multiple hormones. Detailing a comprehensive set of important issues and relevant empirical evidence, this review provides a starting point for best practices in human sexuality research with T and other androgens that may be especially useful for those new to hormone research.

Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

PubMed

Jing, Lijun; Su, Li; Ring, Brian Z

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed.

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.

Assessment of the effects of lacosamide on sleep parameters in healthy subjects.

PubMed

Hudson, J Douglas; Guptill, Jeffrey T; Byrnes, William; Yates, Stephen L; Williams, Paulette; D'Cruz, O'Neill

2015-02-01

Seizures and antiepileptic drugs (AED) may disrupt sleep patterns in patients with epilepsy, thus evaluation of lacosamide effects on objective and subjective sleep measures is warranted. A multicenter, interventional, open-label study (NCT01530386) was conducted in healthy subjects without confounding effects of concomitant AED use, co-morbidities, or disease state to determine whether lacosamide impacts sleep parameters after 22 days of lacosamide exposure. After overnight polysomnography (PSG) to assess baseline parameters, lacosamide was initiated at 100mg/day (50mg twice daily) and increased by 100mg/day weekly to 300 mg/day (the mid-range maintenance dose for adjunctive therapy). The primary variable was change from baseline to post-treatment in wake after sleep onset (WASO). Secondary variables included additional objective sleep measures, subject-reported measures of sleep quality, daytime sleepiness, and tolerability. Change from baseline in WASO was analyzed using the Wilcoxon rank-sum test. A total of 27 subjects received ≥1 dose of lacosamide and 25 subjects completed the study. For WASO, median change from baseline was a 6-min reduction (95% confidence interval: -38, 77.5; p=0.1074) after lacosamide treatment; this was considered not clinically relevant. No clinically relevant changes were observed in any secondary variables. Thirteen subjects (48%) reported a treatment-emergent adverse event, none of which was severe or led to study discontinuation. Lacosamide 300 mg/day had no effect on objective or subjective sleep parameters in healthy subjects and was generally well tolerated. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Anesthesia in Experimental Stroke Research

PubMed Central

Hoffmann, Ulrike; Sheng, Huaxin; Ayata, Cenk; Warner, David S.

2016-01-01

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke. PMID:27534542

The impact of confounder selection in propensity scores when applied to prospective cohort studies in pregnancy.

PubMed

Xu, Ronghui; Hou, Jue; Chambers, Christina D

2018-06-01

Our work was motivated by small cohort studies on the risk of birth defects in infants born to pregnant women exposed to medications. We controlled for confounding using propensity scores (PS). The extremely rare events setting renders the matching or stratification infeasible. In addition, the PS itself may be formed via different approaches to select confounders from a relatively long list of potential confounders. We carried out simulation experiments to compare different combinations of approaches: IPW or regression adjustment, with 1) including all potential confounders without selection, 2) selection based on univariate association between the candidate variable and the outcome, 3) selection based on change in effects (CIE). The simulation showed that IPW without selection leads to extremely large variances in the estimated odds ratio, which help to explain the empirical data analysis results that we had observed. Copyright © 2018 Elsevier Inc. All rights reserved.

Eco-HAB as a fully automated and ecologically relevant assessment of social impairments in mouse models of autism.

PubMed

Puścian, Alicja; Łęski, Szymon; Kasprowicz, Grzegorz; Winiarski, Maciej; Borowska, Joanna; Nikolaev, Tomasz; Boguszewski, Paweł M; Lipp, Hans-Peter; Knapska, Ewelina

2016-10-12

Eco-HAB is an open source, RFID-based system for automated measurement and analysis of social preference and in-cohort sociability in mice. The system closely follows murine ethology. It requires no contact between a human experimenter and tested animals, overcoming the confounding factors that lead to irreproducible assessment of murine social behavior between laboratories. In Eco-HAB, group-housed animals live in a spacious, four-compartment apparatus with shadowed areas and narrow tunnels, resembling natural burrows. Eco-HAB allows for assessment of the tendency of mice to voluntarily spend time together in ethologically relevant mouse group sizes. Custom-made software for automated tracking, data extraction, and analysis enables quick evaluation of social impairments. The developed protocols and standardized behavioral measures demonstrate high replicability. Unlike classic three-chambered sociability tests, Eco-HAB provides measurements of spontaneous, ecologically relevant social behaviors in group-housed animals. Results are obtained faster, with less manpower, and without confounding factors.

Regular Tooth Brushing is Associated with a Decreased Risk of Metabolic Syndrome According to a Medical Check-Up Database.

PubMed

Tsutsumi, Chiyo; Kakuma, Tatsuyuki

2015-01-01

Associations have been reported between periodontal disease and increased cardiovascular disease risk, as well as between healthy self-reported tooth brushing behavior and reduced cardiovascular disease risk. We examined the association between self-reported tooth brushing behavior and the risk of metabolic syndrome (MetS) using a large medical check-up database. A total of 12,548 medical checkup records from a medical screening center in a city in southwest Japan were assessed. Subjects were aged 30 to 59 years. As lifestyle is associated with both tooth brushing and MetS, many lifestyle variables were considered as potential confounders. Logistic regression model were employed with a list of 127 lifestyle variables. Twenty variables associated with both tooth brushing and MetS were selected for both males and females. Furthermore, final confounding variables were selected by principal component analysis to avoid collinearity problems. The association of tooth brushing and MetS was evaluated for males and females separately by calculating adjusted odds ratios (ORs) with selected confounders plus age. The association between daily tooth brushing frequency and MetS risk for both genders was significant after adjusting for confounders, with the risk of MetS decreasing with increased frequency of daily tooth brushing (adjusted OR = 0.57 (95%Cl:0.48-0.81), 0.50 (95%Cl:0.35-0.71), 0.42 (95%Cl: 0.29-0.61) for males and adjusted OR = 0.65 (95%Cl:0.48-0.87), 0.44 (95%Cl:0.32-0.62) for females). Therefore, oral hygiene, including the frequency of tooth brushing as a significant component, may be an important factor in preventing MetS.

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

Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data

PubMed Central

Krzystanek, Marcin; Szallasi, Zoltan; Eklund, Aron C.

2013-01-01

Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may have been driven by a confounding technical variable. This approach can be used as a quality control step to identify data sets that are likely to yield false positive results. PMID:23613961

Bilingualism and Cognitive Reserve: A Critical Overview and a Plea for Methodological Innovations

PubMed Central

Calvo, Noelia; García, Adolfo M.; Manoiloff, Laura; Ibáñez, Agustín

2016-01-01

The decline of cognitive skills throughout healthy or pathological aging can be slowed down by experiences which foster cognitive reserve (CR). Recently, some studies on Alzheimer's disease have suggested that CR may be enhanced by life-long bilingualism. However, the evidence is inconsistent and largely based on retrospective approaches featuring several methodological weaknesses. Some studies demonstrated at least 4 years of delay in dementia symptoms, while others did not find such an effect. Moreover, various methodological aspects vary from study to study. The present paper addresses contradictory findings, identifies possible lurking variables, and outlines methodological alternatives thereof. First, we characterize possible confounding factors that may have influenced extant results. Our focus is on the criteria to establish bilingualism, differences in sample design, the instruments used to examine cognitive skills, and the role of variables known to modulate life-long cognition. Second, we propose that these limitations could be largely circumvented through experimental approaches. Proficiency in the non-native language can be successfully assessed by combining subjective and objective measures; confounding variables which have been distinctively associated with certain bilingual groups (e.g., alcoholism, sleep disorders) can be targeted through relevant instruments; and cognitive status might be better tapped via robust cognitive screenings and executive batteries. Moreover, future research should incorporate tasks yielding predictable patterns of contrastive performance between bilinguals and monolinguals. Crucially, these include instruments which reveal bilingual disadvantages in vocabulary, null effects in working memory, and advantages in inhibitory control and other executive functions. Finally, paradigms tapping proactive interference (which assess the disruptive effect of long-term memory on newly learned information) could also offer useful data, since this phenomenon seems to be better managed by bilinguals and it becomes conspicuous in early stages of dementia. Such considerations may shed light not just on the relationship between bilingualism and CR, but also on more general mechanisms of cognitive compensation. PMID:26793100

Bilingualism and Cognitive Reserve: A Critical Overview and a Plea for Methodological Innovations.

PubMed

Calvo, Noelia; García, Adolfo M; Manoiloff, Laura; Ibáñez, Agustín

2015-01-01

The decline of cognitive skills throughout healthy or pathological aging can be slowed down by experiences which foster cognitive reserve (CR). Recently, some studies on Alzheimer's disease have suggested that CR may be enhanced by life-long bilingualism. However, the evidence is inconsistent and largely based on retrospective approaches featuring several methodological weaknesses. Some studies demonstrated at least 4 years of delay in dementia symptoms, while others did not find such an effect. Moreover, various methodological aspects vary from study to study. The present paper addresses contradictory findings, identifies possible lurking variables, and outlines methodological alternatives thereof. First, we characterize possible confounding factors that may have influenced extant results. Our focus is on the criteria to establish bilingualism, differences in sample design, the instruments used to examine cognitive skills, and the role of variables known to modulate life-long cognition. Second, we propose that these limitations could be largely circumvented through experimental approaches. Proficiency in the non-native language can be successfully assessed by combining subjective and objective measures; confounding variables which have been distinctively associated with certain bilingual groups (e.g., alcoholism, sleep disorders) can be targeted through relevant instruments; and cognitive status might be better tapped via robust cognitive screenings and executive batteries. Moreover, future research should incorporate tasks yielding predictable patterns of contrastive performance between bilinguals and monolinguals. Crucially, these include instruments which reveal bilingual disadvantages in vocabulary, null effects in working memory, and advantages in inhibitory control and other executive functions. Finally, paradigms tapping proactive interference (which assess the disruptive effect of long-term memory on newly learned information) could also offer useful data, since this phenomenon seems to be better managed by bilinguals and it becomes conspicuous in early stages of dementia. Such considerations may shed light not just on the relationship between bilingualism and CR, but also on more general mechanisms of cognitive compensation.

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.

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

Assessing Omitted Confounder Bias in Multilevel Mediation Models.

PubMed

Tofighi, Davood; Kelley, Ken

2016-01-01

To draw valid inference about an indirect effect in a mediation model, there must be no omitted confounders. No omitted confounders means that there are no common causes of hypothesized causal relationships. When the no-omitted-confounder assumption is violated, inference about indirect effects can be severely biased and the results potentially misleading. Despite the increasing attention to address confounder bias in single-level mediation, this topic has received little attention in the growing area of multilevel mediation analysis. A formidable challenge is that the no-omitted-confounder assumption is untestable. To address this challenge, we first analytically examined the biasing effects of potential violations of this critical assumption in a two-level mediation model with random intercepts and slopes, in which all the variables are measured at Level 1. Our analytic results show that omitting a Level 1 confounder can yield misleading results about key quantities of interest, such as Level 1 and Level 2 indirect effects. Second, we proposed a sensitivity analysis technique to assess the extent to which potential violation of the no-omitted-confounder assumption might invalidate or alter the conclusions about the indirect effects observed. We illustrated the methods using an empirical study and provided computer code so that researchers can implement the methods discussed.

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.

Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs.

PubMed

Khan, Jenna; Lieberman, Joshua A; Lockwood, Christina M

2017-05-01

microRNAs (miRNAs) hold promise as biomarkers for a variety of disease processes and for determining cell differentiation. These short RNA species are robust, survive harsh treatment and storage conditions and may be extracted from blood and tissue. Pre-analytical variables are critical confounders in the analysis of miRNAs: we elucidate these and identify best practices for minimizing sample variation in blood and tissue specimens. Pre-analytical variables addressed include patient-intrinsic variation, time and temperature from sample collection to storage or processing, processing methods, contamination by cells and blood components, RNA extraction method, normalization, and storage time/conditions. For circulating miRNAs, hemolysis and blood cell contamination significantly affect profiles; samples should be processed within 2 h of collection; ethylene diamine tetraacetic acid (EDTA) is preferred while heparin should be avoided; samples should be "double spun" or filtered; room temperature or 4 °C storage for up to 24 h is preferred; miRNAs are stable for at least 1 year at -20 °C or -80 °C. For tissue-based analysis, warm ischemic time should be <1 h; cold ischemic time (4 °C) <24 h; common fixative used for all specimens; formalin fix up to 72 h prior to processing; enrich for cells of interest; validate candidate biomarkers with in situ visualization. Most importantly, all specimen types should have standard and common workflows with careful documentation of relevant pre-analytical variables.

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.

Interpretational Confounding Is Due to Misspecification, Not to Type of Indicator: Comment on Howell, Breivik, and Wilcox (2007)

ERIC Educational Resources Information Center

Bollen, Kenneth A.

2007-01-01

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…

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.

Polychlorinated biphenyl exposure and effects in transformer repair workers.

PubMed Central

Emmett, E A

1985-01-01

Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower. Statistically significant differences in serum albumin and lactic dehydrogenase, but not in other liver function tests, were seen between the exposed and comparison groups; however, after adjustment for confounding variables, no correlations were observed between liver function tests and either adipose or serum PCBs concentrations. Statistically significant correlation both before and after adjustment for confounding variables were seen with adipose PCBs and 24-hr urinary 17-hydroxycorticosteroid excretion and with serum PCBs and serum gamma-glutamyl transpeptidase. Both associations could reflect microsomal enzyme induction among other possibilities. No differences were seen in fasting serum triglycerides, total cholesterol, LDL, HDL or VLDL cholesterol between the two exposure groups. A statistically significant correlation between serum PCBs and serum triglycerides, total cholesterol, and VLDL cholesterol was removed by adjusting for confounding variables. No correlation was seen between adipose PCBs concentrations and any serum lipid component. Partition phenomena could account for these findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2863134

On causal interpretation of race in regressions adjusting for confounding and mediating variables

PubMed Central

VanderWeele, Tyler J.; Robinson, Whitney R.

2014-01-01

We consider several possible interpretations of the “effect of race” when regressions are run with race as an exposure variable, controlling also for various confounding and mediating variables. When adjustment is made for socioeconomic status early in a person’s life, we discuss under what contexts the regression coefficients for race can be interpreted as corresponding to the extent to which a racial inequality would remain if various socioeconomic distributions early in life across racial groups could be equalized. When adjustment is also made for adult socioeconomic status, we note how the overall racial inequality can be decomposed into the portion that would be eliminated by equalizing adult socioeconomic status across racial groups and the portion of the inequality that would remain even if adult socioeconomic status across racial groups were equalized. We also discuss a stronger interpretation of the “effect of race” (stronger in terms of assumptions) involving the joint effects of race-associated physical phenotype (e.g. skin color), parental physical phenotype, genetic background and cultural context when such variables are thought to be hypothetically manipulable and if adequate control for confounding were possible. We discuss some of the challenges with such an interpretation. Further discussion is given as to how the use of selected populations in examining racial disparities can additionally complicate the interpretation of the effects. PMID:24887159

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.

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.

Ecomorphology and phylogenetic risk: Implications for habitat reconstruction using fossil bovids.

PubMed

Scott, Robert S; Barr, W Andrew

2014-08-01

Reconstructions of paleohabitats are necessary aids in understanding hominin evolution. The morphology of species from relevant sites, understood in terms of functional relationships to habitat (termed ecomorphology), offers a direct link to habitat. Bovids are a speciose radiation that includes many habitat specialists and are abundant in the fossil record. Thus, bovids are extremely common in ecomorphological analyses. However, bovid phylogeny and habitat preference are related, which raises the possibility that analyses linking habitat with morphology are not 'taxon free' but 'taxon-dependent.' Here we analyze eight relative dimensions and one shape index of the metatarsal for a sample of 72 bovid species and one antilocaprid. The selected variables have been previously shown to have strong associations with habitat and to have functional explanations for these associations. Phylogenetic generalized least squares analyses of these variables, including habitat and size, resulted in estimates for the parameter lambda (used to model phylogenetic signal) varying from zero to one. Thus, while phylogeny, morphology, and habitat all march together among the bovids, the odds that phylogeny confounds ecomorphological analyses may vary depending on particular morphological characteristics. While large values of lambda do not necessarily indicate that habitat differences are unimportant drivers of morphology, we consider the low value of lambda for relative metatarsal width suggestive that conclusions about habitat built on observations of this particular morphology carry with them less 'phylogenetic risk.' We suggest that the way forward for ecomorphology is grounded in functionally relevant observations and careful consideration of phylogeny designed to bracket probable habitat preferences appropriately. Separate consideration of different morphological variables may help to determine the level of 'phylogenetic risk' attached to conclusions linking habitat and morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Eco-HAB as a fully automated and ecologically relevant assessment of social impairments in mouse models of autism

PubMed Central

Puścian, Alicja; Łęski, Szymon; Kasprowicz, Grzegorz; Winiarski, Maciej; Borowska, Joanna; Nikolaev, Tomasz; Boguszewski, Paweł M; Lipp, Hans-Peter; Knapska, Ewelina

2016-01-01

Eco-HAB is an open source, RFID-based system for automated measurement and analysis of social preference and in-cohort sociability in mice. The system closely follows murine ethology. It requires no contact between a human experimenter and tested animals, overcoming the confounding factors that lead to irreproducible assessment of murine social behavior between laboratories. In Eco-HAB, group-housed animals live in a spacious, four-compartment apparatus with shadowed areas and narrow tunnels, resembling natural burrows. Eco-HAB allows for assessment of the tendency of mice to voluntarily spend time together in ethologically relevant mouse group sizes. Custom-made software for automated tracking, data extraction, and analysis enables quick evaluation of social impairments. The developed protocols and standardized behavioral measures demonstrate high replicability. Unlike classic three-chambered sociability tests, Eco-HAB provides measurements of spontaneous, ecologically relevant social behaviors in group-housed animals. Results are obtained faster, with less manpower, and without confounding factors. DOI: http://dx.doi.org/10.7554/eLife.19532.001 PMID:27731798

A comparison of spectral mixture analysis an NDVI for ascertaining ecological variables

NASA Technical Reports Server (NTRS)

Wessman, Carol A.; Bateson, C. Ann; Curtiss, Brian; Benning, Tracy L.

1993-01-01

In this study, we compare the performance of spectral mixture analysis to the Normalized Difference Vegetation Index (NDVI) in detecting change in a grassland across topographically-induced nutrient gradients and different management schemes. The Konza Prairie Research Natural Area, Kansas, is a relatively homogeneous tallgrass prairie in which change in vegetation productivity occurs with respect to topographic positions in each watershed. The area is the site of long-term studies of the influence of fire and grazing on tallgrass production and was the site of the First ISLSCP (International Satellite Land Surface Climatology Project) Field Experiment (FIFE) from 1987 to 1989. Vegetation indices such as NDVI are commonly used with imagery collected in few (less than 10) spectral bands. However, the use of only two bands (e.g. NDVI) does not adequately account for the complex of signals making up most surface reflectance. Influences from background spectral variation and spatial heterogeneity may confound the direct relationship with biological or biophysical variables. High dimensional multispectral data allows for the application position of techniques such as derivative analysis and spectral curve fitting, thereby increasing the probability of successfully modeling the reflectance from mixed surfaces. The higher number of bands permits unmixing of a greater number of surface components, separating the vegetation signal for further analyses relevant to biological variables.

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.

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

PubMed Central

Zandvliet, Maarten L.; Koolen, Stijn L. W.; Mathijssen, Ron H. J.; van der Rijt, Carin C. D.

2016-01-01

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer‐related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter‐ and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side‐effects and increasing its efficacy. PMID:27619152

Dynamic Brain Network Correlates of Spontaneous Fluctuations in Attention.

PubMed

Kucyi, Aaron; Hove, Michael J; Esterman, Michael; Hutchison, R Matthew; Valera, Eve M

2017-03-01

Human attention is intrinsically dynamic, with focus continuously shifting between elements of the external world and internal, self-generated thoughts. Communication within and between large-scale brain networks also fluctuates spontaneously from moment to moment. However, the behavioral relevance of dynamic functional connectivity and possible link with attentional state shifts is unknown. We used a unique approach to examine whether brain network dynamics reflect spontaneous fluctuations in moment-to-moment behavioral variability, a sensitive marker of attentional state. Nineteen healthy adults were instructed to tap their finger every 600 ms while undergoing fMRI. This novel, but simple, approach allowed us to isolate moment-to-moment fluctuations in behavioral variability related to attention, independent of common confounds in cognitive tasks (e.g., stimulus changes, response inhibition). Spontaneously increasing tap variance ("out-of-the-zone" attention) was associated with increasing activation in dorsal-attention and salience network regions, whereas decreasing tap variance ("in-the-zone" attention) was marked by increasing activation of default mode network (DMN) regions. Independent of activation, tap variance representing out-of-the-zone attention was also time-locked to connectivity both within DMN and between DMN and salience network regions. These results provide novel mechanistic data on the understudied neural dynamics of everyday, moment-to-moment attentional fluctuations, elucidating the behavioral importance of spontaneous, transient coupling within and between attention-relevant networks. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study

PubMed Central

Hart, Carole L; Hole, David J; Lawlor, Debbie A; Smith, George Davey; Lever, Tony F

2007-01-01

Objectives To investigate how loss of a spouse affects mortality risk in the bereaved partner. Design and setting Prospective cohort study in Renfrew and Paisley in Scotland. Participants 4395 married couples aged 45–64 years when the study was carried out between 1972 and 1976. Methods The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow‐up period, so it was considered as a time‐dependent exposure variable and the Cox proportional hazards model for time‐dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non‐bereaved spouses and adjusted for confounding variables. Main outcome measures Causes of death to 31 March 2004. Results Bereaved participants were at higher risk than non‐bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking‐related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement. Conclusions Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death. PMID:17435215

Negative control exposure studies in the presence of measurement error: implications for attempted effect estimate calibration

PubMed Central

Sanderson, Eleanor; Macdonald-Wallis, Corrie; Davey Smith, George

2018-01-01

Abstract Background Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome. Methods We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations. Results Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study. Conclusions Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present. PMID:29088358

Negative control exposure studies in the presence of measurement error: implications for attempted effect estimate calibration.

PubMed

Sanderson, Eleanor; Macdonald-Wallis, Corrie; Davey Smith, George

2018-04-01

Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome. We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations. Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study. Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present.

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.

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.

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.

Reconsidering formative measurement.

PubMed

Howell, Roy D; Breivik, Einar; Wilcox, James B

2007-06-01

The relationship between observable responses and the latent constructs they are purported to measure has received considerable attention recently, with particular focus on what has become known as formative measurement. This alternative to reflective measurement in the area of theory-testing research is examined in the context of the potential for interpretational confounding and a construct's ability to function as a point variable within a larger model. Although these issues have been addressed in the traditional reflective measurement context, the authors suggest that they are particularly relevant in evaluating formative measurement models. On the basis of this analysis, the authors conclude that formative measurement is not an equally attractive alternative to reflective measurement and that whenever possible, in developing new measures or choosing among alternative existing measures, researchers should opt for reflective measurement. In addition, the authors provide guidelines for researchers dealing with existing formative measures. Copyright 2007 APA, all rights reserved.

Sources of indoor air pollution and respiratory health in preschool children.

PubMed

Fuentes-Leonarte, Virginia; Ballester, Ferran; Tenías, José Maria

2009-01-01

We carried out bibliographic searches in PubMed and Embase.com for the period from 1996 to 2008 with the aim of reviewing the scientific literature on the relationship between various sources of indoor air pollution and the respiratory health of children under the age of five. Those studies that included adjusted correlation measurements for the most important confounding variables and which had an adequate population size were considered to be more relevant. The results concerning the relationship between gas energy sources and children's respiratory health were heterogeneous. Indoor air pollution from biomass combustion in the poorest countries was found to be an important risk factor for lower respiratory tract infections. Solvents involved in redecorating, DYI work, painting, and so forth, were found to be related to an increased risk for general respiratory problems. The distribution of papers depending on the pollution source showed a clear relationship with life-style and the level of development.

Winners, Losers, Insiders, and Outsiders: Comparing Hierometer and Sociometer Theories of Self-Regard

PubMed Central

Mahadevan, Nikhila; Gregg, Aiden P.; Sedikides, Constantine; de Waal-Andrews, Wendy G.

2016-01-01

What evolutionary function does self-regard serve? Hierometer theory, introduced here, provides one answer: it helps individuals navigate status hierarchies, which feature zero-sum contests that can be lost as well as won. In particular, self-regard tracks social status to regulate behavioral assertiveness, augmenting or diminishing it to optimize performance in such contests. Hierometer theory also offers a conceptual counterpoint that helps resolve ambiguities in sociometer theory, which offers a complementary account of self-regard’s evolutionary function. In two large-scale cross-sectional studies, we operationalized theoretically relevant variables at three distinct levels of analysis, namely, social (relations: status, inclusion), psychological (self-regard: self-esteem, narcissism), and behavioral (strategy: assertiveness, affiliativeness). Correlational and mediational analyses consistently supported hierometer theory, but offered only mixed support for sociometer theory, including when controlling for confounding constructs (anxiety, depression). We interpret our results in terms of a broader agency-communion framework. PMID:27065896

[Adoption of new technologies by health services: the challenge of analyzing relevant factors].

PubMed

Trindade, Evelinda

2008-05-01

The exponential increase in the incorporation of health technologies has been considered a key factor in increased expenditures by the health sector. Such decisions involve multiple levels and stakeholders. Decentralization has multiplied the decision-making levels, with numerous difficult choices and limited resources. The interrelationship between stakeholders is complex, in creative systems with multiple determinants and confounders. The current review discusses the interaction between the factors influencing the decisions to incorporate technologies by health services, and proposes a structure for their analysis. The application and intensity of these factors in decision-making and the incorporation of products and programs by health services shapes the installed capacity of local and regional networks and modifies the health system. Empirical observation of decision-making and technology incorporation in Brazilian health services poses an important challenge. The structured recognition and measurement of these variables can assist proactive planning of health services.

Fatigue and crashes: the case of freight transport in Colombia.

PubMed

Torregroza-Vargas, Nathaly M; Bocarejo, Juan Pablo; Ramos-Bonilla, Juan P

2014-11-01

Truck drivers have been involved in a significant number of road fatalities in Colombia. To identify variables that could be associated with crashes in which truck drivers are involved, a logistic regression model was constructed. The model had as the response variable a dichotomous variable that included the presence or absence of a crash during a specific trip. As independent variables the model included information regarding a driver's work shift, with variables that could be associated with driver's fatigue. The model also included potential confounders related with road conditions. With the model, it was possible to determine the odds ratio of a crash in relation to several variables, adjusting for confounding. To collect the information about the trips included in the model, a survey among truck drivers was conducted. The results suggest strong associations between crashes (i.e., some of them statistically significant) with the number of stops made during the trip, and the average time of each stop. Survey analysis allowed us to identify the practices that contribute to generating fatigue and unhealthy conditions on the road among professional drivers. A review of national regulations confirmed the lack of legislation on this topic. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficient estimation of the attributable fraction when there are monotonicity constraints and interactions.

PubMed

Traskin, Mikhail; Wang, Wei; Ten Have, Thomas R; Small, Dylan S

2013-01-01

The PAF for an exposure is the fraction of disease cases in a population that can be attributed to that exposure. One method of estimating the PAF involves estimating the probability of having the disease given the exposure and confounding variables. In many settings, the exposure will interact with the confounders and the confounders will interact with each other. Also, in many settings, the probability of having the disease is thought, based on subject matter knowledge, to be a monotone increasing function of the exposure and possibly of some of the confounders. We develop an efficient approach for estimating logistic regression models with interactions and monotonicity constraints, and apply this approach to estimating the population attributable fraction (PAF). Our approach produces substantially more accurate estimates of the PAF in some settings than the usual approach which uses logistic regression without monotonicity constraints.

THE EXPERIMENTAL DESIGN FOR BeO IRAADIATION EXPERIMENTS ORNL 41-8 AND ORNL 41-9

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

Gardiner, D.A.

1962-07-18

The experimental plan for irradiating BeO pellets in Experiments ORNL 41- 8 and ORNL 41-9 was chosen in accordance with the principles of experimental design. The design is known by statisticians as a 2/sup 5/ factorial experiment confound'' in six replications. Five variables---size, density, grain size, temperature and time--are controlled at two levels to form the basic 2i factorial experiment. The sixth variable, neutron flux, is introduced by confounding on higher-order interactions. An explanation is presented in nontechnical language the means by which the aims of the experimenters and the physical conditions affecting the experiment were utilized in constructing themore » experimental design. (auth)« less

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…

Beyond Free Lunch: Which Family Background Measures Matter?

ERIC Educational Resources Information Center

Lubienski, Sarah Theule; Crane, Corinna Crawford

2010-01-01

Most studies of school achievement use free-lunch eligibility or other basic indicators to adjust for differences in students' socioeconomic backgrounds. This study determines whether these variables are enough to separate the confounding effects of students' backgrounds from the main variables of interest in education studies. The Early Childhood…

The Causal Mediation Formula - A Guide to the Assessment of Pathways and Mechanisms

DTIC Science & Technology

2011-10-01

for estimating CDE(z) in observational studies (in the presence of unobserved confounders) can be derived using do- calculus (Pearl, 2009, pp. 85–88...2011; Albert and Nelson , 2011). 7In the presence of measured and unmeasured confounders, the general conditions under which NDE is estimable from...achieve this independence (see footnote 7), that Z may represent a vector of variables, and that integrals should replace summations when dealing with

Measuring the surgical 'learning curve': methods, variables and competency.

PubMed

Khan, Nuzhath; Abboudi, Hamid; Khan, Mohammed Shamim; Dasgupta, Prokar; Ahmed, Kamran

2014-03-01

To describe how learning curves are measured and what procedural variables are used to establish a 'learning curve' (LC). To assess whether LCs are a valuable measure of competency. A review of the surgical literature pertaining to LCs was conducted using the Medline and OVID databases. Variables should be fully defined and when possible, patient-specific variables should be used. Trainee's prior experience and level of supervision should be quantified; the case mix and complexity should ideally be constant. Logistic regression may be used to control for confounding variables. Ideally, a learning plateau should reach a predefined/expert-derived competency level, which should be fully defined. When the group splitting method is used, smaller cohorts should be used in order to narrow the range of the LC. Simulation technology and competence-based objective assessments may be used in training and assessment in LC studies. Measuring the surgical LC has potential benefits for patient safety and surgical education. However, standardisation in the methods and variables used to measure LCs is required. Confounding variables, such as participant's prior experience, case mix, difficulty of procedures and level of supervision, should be controlled. Competency and expert performance should be fully defined. © 2013 The Authors. BJU International © 2013 BJU International.

Combining fixed effects and instrumental variable approaches for estimating the effect of psychosocial job quality on mental health: evidence from 13 waves of a nationally representative cohort study.

PubMed

Milner, Allison; Aitken, Zoe; Kavanagh, Anne; LaMontagne, Anthony D; Pega, Frank; Petrie, Dennis

2017-06-23

Previous studies suggest that poor psychosocial job quality is a risk factor for mental health problems, but they use conventional regression analytic methods that cannot rule out reverse causation, unmeasured time-invariant confounding and reporting bias. This study combines two quasi-experimental approaches to improve causal inference by better accounting for these biases: (i) linear fixed effects regression analysis and (ii) linear instrumental variable analysis. We extract 13 annual waves of national cohort data including 13 260 working-age (18-64 years) employees. The exposure variable is self-reported level of psychosocial job quality. The instruments used are two common workplace entitlements. The outcome variable is the Mental Health Inventory (MHI-5). We adjust for measured time-varying confounders. In the fixed effects regression analysis adjusted for time-varying confounders, a 1-point increase in psychosocial job quality is associated with a 1.28-point improvement in mental health on the MHI-5 scale (95% CI: 1.17, 1.40; P < 0.001). When the fixed effects was combined with the instrumental variable analysis, a 1-point increase psychosocial job quality is related to 1.62-point improvement on the MHI-5 scale (95% CI: -0.24, 3.48; P = 0.088). Our quasi-experimental results provide evidence to confirm job stressors as risk factors for mental ill health using methods that improve causal inference. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Stable carbon and nitrogen isotope composition of aquatic and terrestrial plants of the San Francisco Bay estuarine system

USGS Publications Warehouse

Cloern, J.E.; Canuel, E.A.; Harris, D.

2002-01-01

We report measurements of seasonal variability in the C-N stable isotope ratios of plants collected across the habitat mosaic of San Francisco Bay, its marshes, and its tributary river system. Analyses of 868 plant samples were binned into 10 groups (e.g., terrestrial riparian, freshwater phytoplankton, salt marsh) to determine whether C-N isotopes can be used as biomarkers for tracing the origins of organic matter in this river-marsh-estuary complex. Variability of ??13C and ??15N was high (???5-10???) within each plant group, and we identified three modes of variability: (1) between species and their microhabitats, (2) over annual cycles of plant growth and senescence, and (3) between living and decomposing biomass. These modes of within-group variability obscure any source-specific isotopic signatures, confounding the application of C-N isotopes for identifying the origins of organic matter. A second confounding factor was large dissimilarity between the ??13C-??15N of primary producers and the organic-matter pools in the seston and sediments. Both confounding factors impede the application of C-N isotopes to reveal the food supply to primary consumers in ecosystems supporting diverse autotrophs and where the isotopic composition of organic matter has been transformed and become distinct from that of its parent plant sources. Our results support the advice of others: variability of C-N stable isotopes within all organic-matter pools is high and must be considered in applications of these isotopes to trace trophic linkages from primary producers to primary consumers. Isotope-based approaches are perhaps most powerful when used to complement other tools, such as molecular biomarkers, bioassays, direct measures of production, and compilations of organic-matter budgets.

Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

PubMed Central

Jing, Lijun; Su, Li; Ring, Brian Z.

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort’s ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed. PMID:24901479

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.

“Skill of Generalized Additive Model to Detect PM2.5 Health ...

EPA Pesticide Factsheets

Summary. Measures of health outcomes are collinear with meteorology and air quality, making analysis of connections between human health and air quality difficult. The purpose of this analysis was to determine time scales and periods shared by the variables of interest (and by implication scales and periods that are not shared). Hospital admissions, meteorology (temperature and relative humidity), and air quality (PM2.5 and daily maximum ozone) for New York City during the period 2000-2006 were decomposed into temporal scales ranging from 2 days to greater than two years using a complex wavelet transform. Health effects were modeled as functions of the wavelet components of meteorology and air quality using the generalized additive model (GAM) framework. This simulation study showed that GAM is extremely successful at extracting and estimating a health effect embedded in a dataset. It also shows that, if the objective in mind is to estimate the health signal but not to fully explain this signal, a simple GAM model with a single confounder (calendar time) whose smooth representation includes a sufficient number of constraints is as good as a more complex model.Introduction. In the context of wavelet regression, confounding occurs when two or more independent variables interact with the dependent variable at the same frequency. Confounding also acts on a variety of time scales, changing the PM2.5 coefficient (magnitude and sign) and its significance ac

Childhood trauma is not a confounder of the overlap between autistic and schizotypal traits: A study in a non-clinical adult sample.

PubMed

Gong, Jing-Bo; Wang, Ya; Lui, Simon S Y; Cheung, Eric F C; Chan, Raymond C K

2017-11-01

Childhood trauma has been shown to be a robust risk factor for mental disorders, and may exacerbate schizotypal traits or contribute to autistic trait severity. However, little is known whether childhood trauma confounds the overlap between schizotypal traits and autistic traits. This study examined whether childhood trauma acts as a confounding variable in the overlap between autistic and schizotypal traits in a large non-clinical adult sample. A total of 2469 participants completed the Autism Spectrum Quotient (AQ), the Schizotypal Personality Questionnaire (SPQ), and the Childhood Trauma Questionnaire-Short Form. Correlation analysis showed that the majority of associations between AQ variables and SPQ variables were significant (p < 0.05). In the multiple regression models predicting scores on the AQ total, scores on the three SPQ subscales were significant predictors(Ps < 0.05). Scores on the Positive schizotypy and Negative schizotypy subscales were significant predictors in the multiple regression model predicting scores on the AQ Social Skill, AQ Attention Switching, AQ Attention to Detail, AQ Communication, and AQ Imagination subscales. The association between autistic and schizotypal traits could not be explained by shared variance in terms of exposure to childhood trauma. The findings point to important overlaps in the conceptualization of ASD and SSD, independent of childhood trauma. Copyright © 2017 Elsevier B.V. All rights reserved.

Cannabis use and risk of lung cancer: a case-control study.

PubMed

Aldington, S; Harwood, M; Cox, B; Weatherall, M; Beckert, L; Hansell, A; Pritchard, A; Robinson, G; Beasley, R

2008-02-01

The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking. A case-control study of lung cancer in adults

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.

"Fundamental Causes" of Social Inequalities in Mortality: A Test of the Theory

ERIC Educational Resources Information Center

Phelan, Jo C.; Link, Bruce G.; Diez-Roux, Ana; Kawachi, Ichiro; Levin, Bruce

2004-01-01

Medicine and epidemiology currently dominate the study of the strong association between socioeconomic status and mortality. Socioeconomic status typically is viewed as a causally irrelevant "confounding variable" or as a less critical variable marking only the beginning of a causal chain in which intervening risk factors are given prominence. Yet…

Predicting Teacher Value-Added Results in Non-Tested Subjects Based on Confounding Variables: A Multinomial Logistic Regression

ERIC Educational Resources Information Center

Street, Nathan Lee

2017-01-01

Teacher value-added measures (VAM) are designed to provide information regarding teachers' causal impact on the academic growth of students while controlling for exogenous variables. While some researchers contend VAMs successfully and authentically measure teacher causality on learning, others suggest VAMs cannot adequately control for exogenous…

Are Attractive Men's Faces Masculine or Feminine? The Importance of Controlling Confounds in Face Stimuli

ERIC Educational Resources Information Center

Debruine, Lisa M.; Jones, Benedict C.; Smith, Finlay G.; Little, Anthony C.

2010-01-01

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…

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…

Association between prolonged breast-feeding and early childhood caries: a hierarchical approach.

PubMed

Nunes, Ana Margarida Melo; Alves, Claudia Maria Coelho; Borba de Araújo, Fernando; Ortiz, Tânia Mara Lopes; Ribeiro, Marizélia Rodrigues Costa; Silva, Antônio Augusto Moura da; Ribeiro, Cecília Claudia Costa

2012-12-01

This study was conducted to investigate the association between prolonged breastfeeding and early childhood caries(ECC) with adjustment for important confounders, using hieraschical approach. This retrospective cohort study involved 260 low-income children (18-42 months). The number of decayed teeth was used as a measure of caries. Following a theoretical framework, the hierarchical model was built in a forward fashion, by adding the following levels in succession: level 1: age; level 2: social variables; level 3: health variables; level 4: behavioral variables; level 5: oral hygiene-related variables; level 6: oral hygiene quality measured by visible plaque; and level 7: contamination by mutans streptococci. Sequential forward multiple Poisson regression analysis was employed. Breast-feeding was not a risk factor for ECC after adjustment for some confounders (incidence density ratio, 1.15; 95% confidence interval, 0.84-1.59, P = 0.363). Prolonged breast-feeding was not a risk factor for ECC while age, high sucrose comption between main meals and the quality of oral higiene were associated with disease in children. © 2012 John Wiley & Sons A/S.

Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

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

First measurements of the scope for growth (SFG) in mussels from a large scale survey in the North-Atlantic Spanish coast.

PubMed

Albentosa, Marina; Viñas, Lucía; Besada, Victoria; Franco, Angeles; González-Quijano, Amelia

2012-10-01

SFG and physiological rates were measured in wild mussels from the Spanish Marine Pollution monitoring program (SMP) in order to determine seawater quality. It consists of 41 stations, covering almost 2500 km of coast, making the SMP the widest-ranging monitoring network in the Iberian Peninsula's Atlantic region. Results of the 2007 and 2008 surveys when 39 sites were sampled: (20 in 2007 and 19 in 2008, being 8 sites sampled both years) were presented. Chemical analyses were carried out to determine the relationships between physiological rates and the accumulation of toxic compounds. Data presented are the first to become available on the use of SFG as a biomarker of the marine environment on a large spatial scale (>1000 km) along Spain's Atlantic seaboard. SFG values enable significant differences to be established between the areas sampled and between the two years surveyed. The integration of biological and chemical data suggests that certain organochlorine compounds, namely chlordanes and DDTs, may have a negative effect on SFG, although such an effect is of a lesser magnitude than that associated with certain biological parameters such as condition index and mussel age. These variables act as confounding factors when attempting to determine the effect of chemical compounds present in the marine environment on mussel SFG. Further research is therefore needed on the relation between these confounding factors and SFG in order to apply the relevant corrective strategies to enable this index to be used in monitoring programs. The effect of these confounding factors is more clearly revealed in studies that cover a wide-ranging spatial and time scale, such as those carried out within the SMP. These results do not invalidate the use of biological data in monitoring programs, but rather point to the need to analyze all the factors affecting each biological process. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

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.

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.

Oxytocin in the Treatment of Dystocia in Mice

PubMed Central

Narver, Heather L

2012-01-01

Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research. PMID:22330862

Maternal depressive symptoms and early childhood cognitive development: a meta-analysis.

PubMed

Liu, Y; Kaaya, S; Chai, J; McCoy, D C; Surkan, P J; Black, M M; Sutter-Dallay, A-L; Verdoux, H; Smith-Fawzi, M C

2017-03-01

Previous findings have been mixed regarding the relationship between maternal depressive symptoms and child cognitive development. The objective of this study was to systematically review relevant literature and to perform a meta-analysis. Three electronic databases (PubMed, EMBASE, PsycINFO) were searched. Initial screening was conducted independently by two reviewers. Studies selected for detailed review were read in full and included based on a set of criteria. Data from selected studies were abstracted onto a standardized form. Meta-analysis using the inverse variance approach and random-effects models was conducted. The univariate analysis of 14 studies revealed that maternal depressive symptoms are related to lower cognitive scores among children aged ⩽56 months (Cohen's d = -0.25, 95% CI -0.39 to -0.12). The synthesis of studies controlling for confounding variables showed that the mean cognitive score for children 6-8 weeks post-partum whose mothers had high depressive symptoms during the first few weeks postpartum was approximately 4.2 units lower on the Mental Developmental Index (MDI) of the Bayley Scales of Infant and Toddler Development (BSID) compared with children with non-symptomatic mothers (B̂ = -4.17, 95% CI -8.01 to -0.32). The results indicated that maternal depressive symptoms are related to lower cognitive scores in early infancy, after adjusting for confounding factors. An integrated approach for supporting child cognitive development may include program efforts that promote maternal mental health in addition to family economic wellbeing, responsive caregiving, and child nutrition.

Effect of water quality and confounding factors on digestive enzyme activities in Gammarus fossarum.

PubMed

Charron, L; Geffard, O; Chaumot, A; Coulaud, R; Queau, H; Geffard, A; Dedourge-Geffard, O

2013-12-01

The feeding activity and subsequent assimilation of the products resulting from food digestion allow organisms to obtain energy for growth, maintenance and reproduction. Among these biological parameters, we studied digestive enzymes (amylase, cellulase and trypsin) in Gammarus fossarum to assess the impact of contaminants on their access to energy resources. However, to enable objective assessment of a toxic effect of decreased water quality on an organisms' digestive capacity, it is necessary to establish reference values based on its natural variability as a function of changing biotic and abiotic factors. To limit the confounding influence of biotic factors, a caging approach with calibrated male organisms from the same population was used. This study applied an in situ deployment at 23 sites of the Rhone basin rivers, complemented by a laboratory experiment assessing the influence of two abiotic factors (temperature and conductivity). The results showed a small effect of conductivity on cellulase activity and a significant effect of temperature on digestive enzyme activity but only at the lowest temperature (7 °C). The experimental conditions allowed us to define an environmental reference value for digestive enzyme activities to select sites where the quality of the water impacted the digestive capacity of the organisms. In addition to the feeding rate, this study showed the relevance of digestive enzymes as biomarkers to be used as an early warning tool to reflect organisms' health and the chemical quality of aquatic ecosystems.

Exploring associations between prenatal solvent exposures and teenage drug and alcohol use: a retrospective cohort study.

PubMed

Gallagher, Lisa G; Webster, Thomas F; Aschengrau, Ann

2017-03-11

Investigating the effects of prenatal and childhood exposures on behavioral health outcomes in adolescence is challenging given the lengthy period between the exposure and outcomes. We conducted a retrospective cohort study in Cape Cod, Massachusetts to evaluate the impact of prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water on the occurrence of risk-taking behaviors as a teenager. An increased occurrence of risk-taking behaviors, particularly illicit drug use, was observed in those highly exposed to PCE. We hypothesized that there may be other sources of prenatal solvent exposure such as maternal consumption of alcoholic beverages during pregnancy which might modify the previously observed associations between PCE and risk-taking behaviors and so we conducted an exploratory analysis using available cohort data. The current report presents the results of these analyses and describes the difficulties in conducting research on long-term behavioral effects of early life exposures. The exploratory analysis compared a referent group of subjects with no early life exposure to PCE or alcohol (n = 242) to subjects with only alcohol exposure (n = 201), subjects with only PCE exposure (n = 361), and subjects with exposure to both PCE and alcohol (n = 302). Surveys completed by the subject's mother included questions on prenatal alcoholic beverage consumption and available confounding variables such as cigarette smoking and marijuana use. Surveys completed by the subjects included questions on risk-taking behaviors such as alcoholic beverage consumption and illicit drug use as a teenager and available confounding variables. PCE exposure was modeled using a leaching and transport algorithm embedded in water distribution system modeling software that estimated the amount of PCE delivered to a subject's residence during gestation and early childhood. Subjects with early life exposure to both PCE and alcohol had an increased risk of using two or more major drugs as a teen (RR = 1.9 (95% CI 1.2, 3.0)) compared to unexposed subjects. Increased risks for only PCE exposure (RR = 1.6 (95% CI 1.0, 2.4) and only alcohol exposure (RR = 1.3 (95% CI 0.7, 2.1)) were also evident but were smaller than the increased risk associated with both exposures. While available confounding variables were controlled, many relevant social risk factors were not obtained due to limitations in the retrospective study design. This exploratory analysis found evidence for an additive effect of early life exposure to PCE and alcohol on the risk of use of multiple illicit drugs as a teenager. Because of numerous limitations in this retrospective study, further research is needed to examine longstanding behavioral effects of early life exposures. To be most informative, this research should involve long-term prospective data collection.

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis.

PubMed

Liu, Tianyi; Nie, Xiaolu; Wu, Zehao; Zhang, Ying; Feng, Guoshuang; Cai, Siyu; Lv, Yaqi; Peng, Xiaoxia

2017-12-29

Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.

Incidence of workers compensation indemnity claims across socio-demographic and job characteristics.

PubMed

Du, Juan; Leigh, J Paul

2011-10-01

We hypothesized that low socioeconomic status, employer-provided health insurance, low wages, and overtime were predictors of reporting workers compensation indemnity claims. We also tested for gender and race disparities. Responses from 17,190 (person-years) Americans participating in the Panel Study of Income Dynamics, 1997-2005, were analyzed with logistic regressions. The dependent variable indicated whether the subject collected benefits from a claim. Odds ratios for men and African-Americans were relatively large and strongly significant predictors of claims; significance for Hispanics was moderate and confounded by education. Odds ratios for variables measuring education were the largest for all statistically significant covariates. Neither low wages nor employer-provided health insurance was a consistent predictor. Due to confounding from the "not salaried" variable, overtime was not a consistently significant predictor. Few studies use nationally representative longitudinal data to consider which demographic and job characteristics predict reporting workers compensation indemnity cases. This study did and tested some common hypotheses about predictors. Copyright © 2011 Wiley-Liss, Inc.

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.

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

CADDIS Volume 4. Data Analysis: Basic Principles & Issues

EPA Pesticide Factsheets

Use of inferential statistics in causal analysis, introduction to data independence and autocorrelation, methods to identifying and control for confounding variables, references for the Basic Principles section of Data Analysis.

Mendelian Randomization.

PubMed

Grover, Sandeep; Del Greco M, Fabiola; Stein, Catherine M; Ziegler, Andreas

2017-01-01

Confounding and reverse causality have prevented us from drawing meaningful clinical interpretation even in well-powered observational studies. Confounding may be attributed to our inability to randomize the exposure variable in observational studies. Mendelian randomization (MR) is one approach to overcome confounding. It utilizes one or more genetic polymorphisms as a proxy for the exposure variable of interest. Polymorphisms are randomly distributed in a population, they are static throughout an individual's lifetime, and may thus help in inferring directionality in exposure-outcome associations. Genome-wide association studies (GWAS) or meta-analyses of GWAS are characterized by large sample sizes and the availability of many single nucleotide polymorphisms (SNPs), making GWAS-based MR an attractive approach. GWAS-based MR comes with specific challenges, including multiple causality. Despite shortcomings, it still remains one of the most powerful techniques for inferring causality.With MR still an evolving concept with complex statistical challenges, the literature is relatively scarce in terms of providing working examples incorporating real datasets. In this chapter, we provide a step-by-step guide for causal inference based on the principles of MR with a real dataset using both individual and summary data from unrelated individuals. We suggest best possible practices and give recommendations based on the current literature.

Clustering Words to Match Conditions: An Algorithm for Stimuli Selection in Factorial Designs

ERIC Educational Resources Information Center

Guasch, Marc; Haro, Juan; Boada, Roger

2017-01-01

With the increasing refinement of language processing models and the new discoveries about which variables can modulate these processes, stimuli selection for experiments with a factorial design is becoming a tough task. Selecting sets of words that differ in one variable, while matching these same words into dozens of other confounding variables…

A review of covariate selection for non-experimental comparative effectiveness research.

PubMed

Sauer, Brian C; Brookhart, M Alan; Roy, Jason; VanderWeele, Tyler

2013-11-01

This paper addresses strategies for selecting variables for adjustment in non-experimental comparative effectiveness research and uses causal graphs to illustrate the causal network that relates treatment to outcome. Variables in the causal network take on multiple structural forms. Adjustment for a common cause pathway between treatment and outcome can remove confounding, whereas adjustment for other structural types may increase bias. For this reason, variable selection would ideally be based on an understanding of the causal network; however, the true causal network is rarely known. Therefore, we describe more practical variable selection approaches based on background knowledge when the causal structure is only partially known. These approaches include adjustment for all observed pretreatment variables thought to have some connection to the outcome, all known risk factors for the outcome, and all direct causes of the treatment or the outcome. Empirical approaches, such as forward and backward selection and automatic high-dimensional proxy adjustment, are also discussed. As there is a continuum between knowing and not knowing the causal, structural relations of variables, we recommend addressing variable selection in a practical way that involves a combination of background knowledge and empirical selection and that uses high-dimensional approaches. This empirical approach can be used to select from a set of a priori variables based on the researcher's knowledge to be included in the final analysis or to identify additional variables for consideration. This more limited use of empirically derived variables may reduce confounding while simultaneously reducing the risk of including variables that may increase bias. Copyright © 2013 John Wiley & Sons, Ltd.

A Review of Covariate Selection for Nonexperimental Comparative Effectiveness Research

PubMed Central

Sauer, Brian C.; Brookhart, Alan; Roy, Jason; Vanderweele, Tyler

2014-01-01

This paper addresses strategies for selecting variables for adjustment in non-experimental comparative effectiveness research (CER), and uses causal graphs to illustrate the causal network that relates treatment to outcome. Variables in the causal network take on multiple structural forms. Adjustment for on a common cause pathway between treatment and outcome can remove confounding, while adjustment for other structural types may increase bias. For this reason variable selection would ideally be based on an understanding of the causal network; however, the true causal network is rarely know. Therefore, we describe more practical variable selection approaches based on background knowledge when the causal structure is only partially known. These approaches include adjustment for all observed pretreatment variables thought to have some connection to the outcome, all known risk factors for the outcome, and all direct causes of the treatment or the outcome. Empirical approaches, such as forward and backward selection and automatic high-dimensional proxy adjustment, are also discussed. As there is a continuum between knowing and not knowing the causal, structural relations of variables, we recommend addressing variable selection in a practical way that involves a combination of background knowledge and empirical selection and that uses the high-dimensional approaches. This empirical approach can be used to select from a set of a priori variables based on the researcher’s knowledge to be included in the final analysis or to identify additional variables for consideration. This more limited use of empirically-derived variables may reduce confounding while simultaneously reducing the risk of including variables that may increase bias. PMID:24006330

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

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.

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

Examining confounding by diet in the association between perfluoroalkyl acids and serum cholesterol in pregnancy

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

Skuladottir, Margret; Ramel, Alfons; Unit for Nutrition Research, Landspitali National University Hospital, Reykjavik

Background: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance. Objective: To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet. Methods: 854 Danish women who gave birth in 1988–89 and provided a blood sample and reported their diet in week 30 of gestation. Results: Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal dietmore » was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend <0.01) with relative difference between the highest and lowest quartile in PFOS and PFOA concentrations ranging between 6% and 25% of mean values. After adjustment for dietary factors both PFOA and PFOS were positively and similarly associated with serum cholesterol (P for trend ≤0.01). For example, the mean increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing women in the highest to lowest quintile of PFOA concentrations. In comparison the mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when comparing women in the highest to lowest quintile of saturated fat intake. Conclusion: In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol. - Highlights: • PFOS and PFOA have consistently been linked with raised serum cholesterol • Clinical relevance remains uncertain and confounding by diet has been suggested • The aim of this study was to address these issues in a cohort of 854 pregnant women • With detailed dietary information we found no indication of such confounding • As predictors cholesterol PFOSA and PFOA were similar to other known risk factors.« less

Task-switching cost and repetition priming: two overlooked confounds in the first-set procedure of the Sternberg paradigm and how they affect memory set-size effects.

PubMed

Jou, Jerwen

2014-10-01

Subjects performed Sternberg-type memory recognition tasks (Sternberg paradigm) in four experiments. Category-instance names were used as learning and testing materials. Sternberg's original experiments demonstrated a linear relation between reaction time (RT) and memory-set size (MSS). A few later studies found no relation, and other studies found a nonlinear relation (logarithmic) between the two variables. These deviations were used as evidence undermining Sternberg's serial scan theory. This study identified two confounding variables in the fixed-set procedure of the paradigm (where multiple probes are presented at test for a learned memory set) that could generate a MSS RT function that was either flat or logarithmic rather than linearly increasing. These two confounding variables were task-switching cost and repetition priming. The former factor worked against smaller memory sets and in favour of larger sets whereas the latter factor worked in the opposite way. Results demonstrated that a null or a logarithmic RT-to-MSS relation could be the artefact of the combined effects of these two variables. The Sternberg paradigm has been used widely in memory research, and a thorough understanding of the subtle methodological pitfalls is crucial. It is suggested that a varied-set procedure (where only one probe is presented at test for a learned memory set) is a more contamination-free procedure for measuring the MSS effects, and that if a fixed-set procedure is used, it is worthwhile examining the RT function of the very first trials across the MSSs, which are presumably relatively free of contamination by the subsequent trials.

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.

Risk factors for recurrent gastroesophageal reflux disease after fundoplication in pediatric patients: a case-control study.

PubMed

Ngerncham, Monawat; Barnhart, Douglas C; Haricharan, Ramanath N; Roseman, Jeffrey M; Georgeson, Keith E; Harmon, Carroll M

2007-09-01

Recurrent gastroesophageal reflux disease (rGERD) is a common problem after fundoplication. Previous studies attempting to identify risk factors for rGERD have failed to control for confounding variables. The purpose of this study was to identify significant risk factors for rGERD after controlling for potential confounding variables. A retrospective, matched case-control study was conducted at a tertiary children's hospital. Cases (n = 116) met 1 of these criteria: reoperation for rGERD, symptomatic rGERD (confirmed by upper gastrointestinal series, esophagogastroduodenoscopy, or pH monitoring), or postoperative reinstitution of antireflux medication for more than 8 weeks. Controls (n = 209) were matched for surgeon, approach (laparoscopic/open), technique (partial/complete), and approximate operative date. Univariate and multivariable associations were analyzed by conditional logistic regression. Significant risk factors for rGERD were age of less than 6 years (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.7-7.5), preoperative hiatal hernia (OR, 3.2; 95% CI, 1.4-7.3), postoperative retching (OR, 5.1; 95% CI, 2.6-10.0), and postoperative esophageal dilatation (OR, 10.8; 95% CI, 1.8-65.4). Interestingly, significant association was not found between neurologic impairment and rGERD after controlling for potential confounding variables. Age of less than 6 years, preoperative hiatal hernia, postoperative retching, and postoperative esophageal dilatation are independently associated with increased risk of rGERD. Neurologic impairment alone does not increase the risk of developing rGERD.

DNA Reactivity as a Mode of Action and Its Relevance to Cancer Risk Assessment

EPA Science Inventory

The ability of a chemical to induce mutations has long been a driver in the cancer risk assessment process. The default strategy has been that mutagenic chemicals demonstrate linear cancer dose responses, especially at low exposure levels. In the absence of additional confounding...

A comparison of two cognitive test paradigms in a penetrating brain injury model.

PubMed

Davis, Angela R; Shear, Deborah A; Chen, Zhiyong; Lu, Xi-Chun M; Tortella, Frank C

2010-05-30

A rat model of penetrating ballistic-like brain injury (PBBI) was recently established to study military-relevant severe traumatic brain injury (TBI). The purpose of this study was to conduct a side-by-side evaluation of two well-established cognitive testing paradigms: the novel object recognition (NOR) task and the Morris water maze (MWM) task. Accordingly, male Sprague-Dawley rats were subjected to PBBI and their cognitive abilities were assessed at 7 and 21 days post-PBBI. Although PBBI animals had more difficulty completing both tasks compared to sham animals, their performance on the NOR task was confounded by a high degree of within-group variability that was likely due to attention deficits produced by the injury. In contrast, PBBI produced consistent, significant spatial learning deficits in the MWM task. Overall, these results suggest that the MWM task provides a more appropriate cognitive test for the PBBI model that would be useful for testing promising neuroprotective therapeutics. (c) 2010 Elsevier B.V. All rights reserved.

Prenatal, perinatal, and adolescent exposure to marijuana: Relationships with aggressive behavior.

PubMed

Barthelemy, Olivier J; Richardson, Mark A; Cabral, Howard J; Frank, Deborah A

This manuscript reviews research exploring the relationship between prenatal, perinatal, and adolescent exposure to marijuana and aggressive behavior, including physical aggression. Areas of inquiry include animal research, as well as human research, on prenatal exposure and on marijuana use during adolescence. Potential psychosocial and psychopharmacological mechanisms are identified, as well as relevant confounds. The prenatal marijuana exposure literature provides minimal support for a direct relationship with aggressive behavior in childhood. The adolescent use literature suggests a marginal (at best) association between acute intoxication and aggressive behavior, and an association between chronic use and aggressive behavior heavily influenced by demographic variables, rather than direct, psychopharmacological mechanisms. Cannabis withdrawal symptoms also may include aggression and anger, but there is little evidence to suggest that these effects are large or specific to withdrawal from marijuana compared to other substances. This review will offer recommendations for clinical care and public policy, as well as important questions for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Sources of Indoor Air Pollution and Respiratory Health in Preschool Children

PubMed Central

Fuentes-Leonarte, Virginia; Ballester, Ferran; Tenías, José Maria

2009-01-01

We carried out bibliographic searches in PubMed and Embase.com for the period from 1996 to 2008 with the aim of reviewing the scientific literature on the relationship between various sources of indoor air pollution and the respiratory health of children under the age of five. Those studies that included adjusted correlation measurements for the most important confounding variables and which had an adequate population size were considered to be more relevant. The results concerning the relationship between gas energy sources and children's respiratory health were heterogeneous. Indoor air pollution from biomass combustion in the poorest countries was found to be an important risk factor for lower respiratory tract infections. Solvents involved in redecorating, DYI work, painting, and so forth, were found to be related to an increased risk for general respiratory problems. The distribution of papers depending on the pollution source showed a clear relationship with life-style and the level of development. PMID:20168984

Job Strain and the Cortisol Diurnal Cycle in MESA: Accounting for Between- and Within-Day Variability

PubMed Central

Rudolph, Kara E.; Sánchez, Brisa N.; Stuart, Elizabeth A.; Greenberg, Benjamin; Fujishiro, Kaori; Wand, Gary S.; Shrager, Sandi; Seeman, Teresa; Diez Roux, Ana V.; Golden, Sherita H.

2016-01-01

Evidence of the link between job strain and cortisol levels has been inconsistent. This could be due to failure to account for cortisol variability leading to underestimated standard errors. Our objective was to model the relationship between job strain and the whole cortisol curve, accounting for sources of cortisol variability. Our functional mixed-model approach incorporated all available data—18 samples over 3 days—and uncertainty in estimated relationships. We used employed participants from the Multi-Ethnic Study of Atherosclerosis Stress I Study and data collected between 2002 and 2006. We used propensity score matching on an extensive set of variables to control for sources of confounding. We found that job strain was associated with lower salivary cortisol levels and lower total area under the curve. We found no relationship between job strain and the cortisol awakening response. Our findings differed from those of several previous studies. It is plausible that our results were unique to middle- to older-aged racially, ethnically, and occupationally diverse adults and were therefore not inconsistent with previous research among younger, mostly white samples. However, it is also plausible that previous findings were influenced by residual confounding and failure to propagate uncertainty (i.e., account for the multiple sources of variability) in estimating cortisol features. PMID:26905339

Testing concordance of instrumental variable effects in generalized linear models with application to Mendelian randomization

PubMed Central

Dai, James Y.; Chan, Kwun Chuen Gary; Hsu, Li

2014-01-01

Instrumental variable regression is one way to overcome unmeasured confounding and estimate causal effect in observational studies. Built on structural mean models, there has been considerale work recently developed for consistent estimation of causal relative risk and causal odds ratio. Such models can sometimes suffer from identification issues for weak instruments. This hampered the applicability of Mendelian randomization analysis in genetic epidemiology. When there are multiple genetic variants available as instrumental variables, and causal effect is defined in a generalized linear model in the presence of unmeasured confounders, we propose to test concordance between instrumental variable effects on the intermediate exposure and instrumental variable effects on the disease outcome, as a means to test the causal effect. We show that a class of generalized least squares estimators provide valid and consistent tests of causality. For causal effect of a continuous exposure on a dichotomous outcome in logistic models, the proposed estimators are shown to be asymptotically conservative. When the disease outcome is rare, such estimators are consistent due to the log-linear approximation of the logistic function. Optimality of such estimators relative to the well-known two-stage least squares estimator and the double-logistic structural mean model is further discussed. PMID:24863158

The individualistic fallacy, ecological studies and instrumental variables: a causal interpretation.

PubMed

Loney, Tom; Nagelkerke, Nico J

2014-01-01

The validity of ecological studies in epidemiology for inferring causal relationships has been widely challenged as observed associations could be biased by the Ecological Fallacy. We reconsider the important design components of ecological studies, and discuss the conditions that may lead to spurious associations. Ecological associations are useful and valid when the ecological exposures can be interpreted as Instrumental Variables. A suitable example may be a time series analysis of environmental pollution (e.g. particulate matter with an aerodynamic diameter of <10 micrometres; PM10) and health outcomes (e.g. hospital admissions for acute myocardial infarction) as environmental pollution levels are a cause of individual exposure levels and not just an aggregate measurement. Ecological exposures may also be employed in situations (perhaps rare) where individual exposures are known but their associations with health outcomes are confounded by unknown or unquantifiable factors. Ecological associations have a notorious reputation in epidemiology and individualistic associations are considered superior to ecological associations because of the "ecological fallacy". We have argued that this is incorrect in situations in which ecological or aggregate exposures can serve as an instrumental variable and associations between individual exposure and outcome are likely to be confounded by unmeasured variables.

Tracking Central Hypovolemia with ECG in Humans: Cautions for the Use of Heart Period Variability in Patient Monitoring

DTIC Science & Technology

2010-06-01

without influences that may confound the re- sults (e.g., pain, anxiety , transport conditions, caregiver in- terventions). Second, rather than being...32. Ryan KL, Rickards CA, Muniz GW, Moralez G, Convertino VA: Interindi- vidual variability in heart rate variability ( HRV ) and complexity measure...Raimondi G, Legramante JM, Macerata A: Revisiting the potential of time-domain indexes in short-term HRV analysis. Biomed Tech (Berl) 51:190Y193, 2006

The role of prenatal care and social risk factors in the relationship between immigrant status and neonatal morbidity: a retrospective cohort study.

PubMed

Paz-Zulueta, María; Llorca, Javier; Sarabia-Lavín, Raquel; Bolumar, Francisco; Rioja, Luis; Delgado, Abraham; Santibáñez, Miguel

2015-01-01

Literature evaluating association between neonatal morbidity and immigrant status presents contradictory results. Poorer compliance with prenatal care and greater social risk factors among immigrants could play roles as major confounding variables, thus explaining contradictions. We examined whether prenatal care and social risk factors are confounding variables in the relationship between immigrant status and neonatal morbidity. Retrospective cohort study: 231 pregnant African immigrant women were recruited from 2007-2010 in northern Spain. A Spanish population sample was obtained by simple random sampling at 1:3 ratio. Immigrant status (Spanish, Sub-Saharan and Northern African), prenatal care (Kessner Index adequate, intermediate or inadequate), and social risk factors were treated as independent variables. Low birth weight (LBW < 2500 grams) and preterm birth (< 37 weeks) were collected as neonatal morbidity variables. Crude and adjusted odds ratios (OR) were estimated by unconditional logistic regression with 95% confidence intervals (95% CI). Positive associations between immigrant women and higher risk of neonatal morbidity were obtained. Crude OR for preterm births in Northern Africans with respect to nonimmigrants was 2.28 (95% CI: 1.04-5.00), and crude OR for LBW was 1.77 (95% CI: 0.74-4.22). However, after adjusting for prenatal care and social risk factors, associations became protective: adjusted OR for preterm birth = 0.42 (95% CI: 0.14-1.32); LBW = 0.48 (95% CI: 0.15-1.52). Poor compliance with prenatal care was the main independent risk factor associated with both preterm birth (adjusted OR inadequate care = 17.05; 95% CI: 3.92-74.24) and LBW (adjusted OR inadequate care = 6.25; 95% CI: 1.28-30.46). Social risk was an important independent risk factor associated with LBW (adjusted OR = 5.42; 95% CI: 1.58-18.62). Prenatal care and social risk factors were major confounding variables in the relationship between immigrant status and neonatal morbidity.

Explaining Consumer Safe Food Handling Through Behavior-Change Theories: A Systematic Review.

PubMed

Young, Ian; Reimer, Danielle; Greig, Judy; Meldrum, Richard; Turgeon, Patricia; Waddell, Lisa

2017-11-01

Consumers often engage in unsafe food handling behaviors at home. Previous studies have investigated the ability of behavior-change theories to explain and predict these behaviors. The purpose of this review was to determine which theories are most consistently associated with consumers' safe food handling behaviors across the published literature. A standardized systematic review methodology was used, consisting of the following steps: comprehensive search strategy; relevance screening of identified references; confirmation of relevance and characterization of relevant articles; risk-of-bias assessment; data extraction; and descriptive analysis of study results. A total of 20 relevant studies were identified; they were mostly conducted in Australia (40%) and the United States (35%) and used a cross-sectional design (65%). Most studies targeted young adults (65%), and none focused on high-risk consumer groups. The outcomes of 70% of studies received high overall risk-of-bias ratings, largely due to a lack of control for confounding variables. The most commonly applied theory was the Theory of Planned Behavior (45% of studies), which, along with other investigated theories of behavior change, was frequently associated with consumer safe food handling behavioral intentions and behaviors. However, overall, there was wide variation in the specific constructs found to be significantly associated and in the percentage of variance explained in each outcome across studies. The results suggest that multiple theories of behavior change can help to explain consumer safe food handling behaviors and could be adopted to guide the development of future behavior-change interventions. In these contexts, theories should be appropriately selected and adapted to meet the needs of the specific target population and context of interest.

N-acetyltransferase single nucleotide polymorphisms: Emerging concepts serve as a paradigm for understanding complexities of personalized medicine

PubMed Central

Hein, David W.

2009-01-01

Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) exhibit single nucleotide polymorphisms (SNPs) in human populations that modify drug and carcinogen metabolism. This paper updates the identity, location, and functional effects of these SNPs and then follows with emerging concepts for understanding why pharmacogenetic findings may not be replicated consistently. Using this paradigm as an example, laboratory-based mechanistic analyses can reveal complexities such that genetic polymorphisms become biologically and medically relevant when confounding factors are more fully understood and considered. As medical care moves to a more personalized approach, the implications of these confounding factors will be important in understanding the complexities of personalized medicine. PMID:19379125

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

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

Pot binding as a variable confounding plant phenotype: theoretical derivation and experimental observations.

PubMed

Sinclair, Thomas R; Manandhar, Anju; Shekoofa, Avat; Rosas-Anderson, Pablo; Bagherzadi, Laleh; Schoppach, Remy; Sadok, Walid; Rufty, Thomas W

2017-04-01

Theoretical derivation predicted growth retardation due to pot water limitations, i.e., pot binding. Experimental observations were consistent with these limitations. Combined, these results indicate a need for caution in high-throughput screening and phenotyping. Pot experiments are a mainstay in many plant studies, including the current emphasis on developing high-throughput, phenotyping systems. Pot studies can be vulnerable to decreased physiological activity of the plants particularly when pot volume is small, i.e., "pot binding". It is necessary to understand the conditions under which pot binding may exist to avoid the confounding influence of pot binding in interpreting experimental results. In this paper, a derivation is offered that gives well-defined conditions for the occurrence of pot binding based on restricted water availability. These results showed that not only are pot volume and plant size important variables, but the potting media is critical. Artificial potting mixtures used in many studies, including many high-throughput phenotyping systems, are particularly susceptible to the confounding influences of pot binding. Experimental studies for several crop species are presented that clearly show the existence of thresholds of plant leaf area at which various pot sizes and potting media result in the induction of pot binding even though there may be no immediate, visual plant symptoms. The derivation and experimental results showed that pot binding can readily occur in plant experiments if care is not given to have sufficiently large pots, suitable potting media, and maintenance of pot water status. Clear guidelines are provided for avoiding the confounding effects of water-limited pot binding in studying plant phenotype.

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.

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.

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

Cardiovascular and Cerebrovascular Events Are Associated With Nontraumatic Osteonecrosis of the Femoral Head.

PubMed

Sung, Pei-Hsun; Yang, Yao-Hsu; Chiang, Hsin-Ju; Chiang, John Y; Chen, Chi-Jen; Yip, Hon-Kan; Lee, Mel S

2018-04-01

Endothelial dysfunction has been identified as an etiologic factor for osteonecrosis of the femoral head (ONFH) and major adverse cardiovascular and cerebrovascular events (defined as major cardiovascular disease [CVD] and cerebrovascular accident [CVA]). However, the incidence of major adverse cardiovascular and cerebrovascular events in patients with nontraumatic ONFH and any association between the two diagnoses remain unclear. We compared a large cohort of patients with nontraumatic ONFH and a matched control group without this diagnosis and (1) examined the frequency and hazard ratio (HR) of major adverse cardiovascular and cerebrovascular events in both groups adjusted for age, sex, socioeconomic status, and associated comorbidities (which we defined as the adjusted HR), (2) determined whether any association of ONFH and major adverse cardiovascular and cerebrovascular events was stable after adjusting for confounding variables, and (3) compared the occurrence of major adverse cardiovascular and cerebrovascular events with time in both groups. A population-based cohort with a 14-year dataset period (1997-2010) from the Taiwan National Health Insurance Research Database was used for this retrospective study. The database includes a greater than 99.5% Asian population randomly selected from more than 23 million citizens and foreigners residing in Taiwan for longer than 6 months. A total of 1562 patients with nontraumatic ONFH were identified from a population of one million patients in the database after excluding initially concomitant diagnoses of major CVD and CVA. The comparison group (n = 15,620) without ONFH was analyzed in a one-to-10 ratio by matching the study cohort based on age, sex, income, and urbanization. The patients with ONFH had a higher frequency of major adverse cardiovascular and cerebrovascular events than their counterparts without ONFH (19% versus 14%; p < 0.001). The patients with ONFH had 1.34- and 1.27-fold adjusted HRs for occurrence of major CVD and CVA as compared with the normal population (95% CI, 1.11-1.61, p = 0.002, and 95% CI, 1.09-1.47, p = 0.002, respectively). Sensitivity analysis showed a consistent association between ONFH and major adverse cardiovascular and cerebrovascular events after controlling for potentially relevant confounding variables such as hypertension and diabetes. After adjusting for potential confounders including surgery and medications, ONFH remained independently associated with major CVD (adjusted HR, 1.51, 95% CI 1.09-2.03, p = 0.026) and CVA (adjusted HR, 2.44, 95% CI 1.69-3.51, p < 0.001), apart from age older than 65 years and traditional atherosclerotic risk factors. The cumulative incidence of major adverse cardiovascular and cerebrovascular events also was higher in the ONFH group than the non-ONFH group (30.3% vs 23.1% at the end of followup, p < 0.001). Patients with ONFH have a strong association with major adverse cardiovascular and cerebrovascular events as compared with the normal population, suggesting a potential common pathway involving endothelial dysfunction. In view of this association in the relatively young population with ONFH, it is important to closely monitor these patients, treat relevant comorbidities early, and investigate preventative measures for these major adverse events. Level III, prognostic study.

Blood alcohol concentration is negatively associated with gambling money won on the Iowa gambling task in naturalistic settings after controlling for trait impulsivity and alcohol tolerance.

PubMed

Lyvers, Michael; Mathieson, Nicole; Edwards, Mark S

2015-02-01

Acute alcohol intoxication has been found to increase perseverative errors on the Wisconsin Card Sorting Test, a well known neuropsychological index of prefrontal cortical functioning, in both laboratory and naturalistic settings. The present study examined the relationship between levels of alcohol consumption at campus drinking venues and performance of the Iowa Gambling Task (IGT), another neuropsychological test designed to assess prefrontal cortex dysfunction, after controlling for potential confounding variables including habitual alcohol intake (as a proxy for alcohol tolerance), trait impulsivity, and everyday executive functioning. The 49 participants of both genders aged 18 to 30years were recruited at the relevant venues and showed a broad range of blood alcohol concentrations (BACs) from virtually zero (.002%) to .19%. After controlling for demographic variables, habitual use of alcohol and illicit drugs, and frontal lobe related behavioural traits including impulsivity and disinhibition, BAC negatively predicted gambling money won on the last two trial blocks of the IGT. Trait impulsivity and habitual alcohol use were also significant predictors. Results are discussed in terms of acute effects of alcohol on brain systems and the behavioural consequences of such effects on decision making. Copyright © 2014 Elsevier Ltd. All rights reserved.

The typological approach to submarine groundwater discharge (SGD)

USGS Publications Warehouse

Bokuniewicz, H.; Buddemeier, R.; Maxwell, B.; Smith, C.

2003-01-01

Coastal zone managers need to factor submarine groundwater discharge (SGD) in their integration. SGD provides a pathway for the transfer of freshwater, and its dissolved chemical burden, from the land to the coastal ocean. SGD reduces salinities and provides nutrients to specialized coastal habitats. It also can be a pollutant source, often undetected, causing eutrophication and triggering nuisance algal blooms. Despite its importance, SGD remains somewhat of a mystery in most places because it is usually unseen and difficult to measure. SGD has been directly measured at only about a hundred sites worldwide. A typology generated by the Land-Ocean Interaction in the Coastal Zone (LOICZ) Project is one of the few tools globally available to coastal resource managers for identifying areas in their jurisdiction where SGD may be a confounding process. (LOICZ is a core project of the International Geosphere/Biosphere Programme.) Of the hundreds of globally distributed parameters in the LOICZ typology, a SGD subset of potentially relevant parameters may be culled. A quantitative combination of the relevant hydrological parameters can serve as a proxy for the SGD conditions not directly measured. Web-LOICZ View, geospatial software then provides an automated approach to clustering these data into groups of locations that have similar characteristics. It permits selection of variables, of the number of clusters desired, and of the clustering criteria, and provides means of testing predictive results against independent variables. Information on the occurrence of a variety of SGD indicators can then be incorporated into regional clustering analysis. With such tools, coastal managers can focus attention on the most likely sites of SGD in their jurisdiction and design the necessary measurement and modeling programs needed for integrated management.

Missing variables: how exclusion of human resources policy information confounds research connecting health and business outcomes.

PubMed

Lynch, Wendy D; Sherman, Bruce W

2014-01-01

When corporate health researchers examine the effects of health on business outcomes or the effect of health interventions on health and business outcomes, results will necessarily be confounded by the corporate environment(s) in which they are studied. In this research setting, most studies control for factors traditionally identified in public health, such as demographics and health status. Nevertheless, often overlooked is the extent to which company policies can also independently impact health care cost, work attendance, and productivity outcomes. With changes in employment and benefits practices resulting from health care reform, including incentives and plan design options, consideration of these largely neglected variables in research design has become increasingly important. This commentary summarizes existing knowledge regarding the implications of policy variations in research outcomes and provides a framework for incorporating them into future employer-based research.

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.

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.

No association between partial depopulation and Campylobacter spp. colonization of Dutch broiler flocks.

PubMed

Russa, A D; Bouma, A; Vernooij, J C M; Jacobs-Reitsma, W; Stegeman, J A

2005-01-01

To determine whether an association exists between partial depopulation of a flock and increased Campylobacter colonization in that flock. Data from 1737 flocks of two Dutch integrators were used. Flocks that experienced partial depopulation were defined as 'exposed' and those that did not as 'nonexposed'. Multivariable modelling was accomplished with, in addition to 'exposure', the independent variables 'age of broilers at slaughter' and 'season' to adjust for possible confounding. The response variable was 'Campylobacter colonization'. The odds ratio (OR) for partial depopulation for integrator A was 0.8 [95% CI (0.4, 1.8)]; for integrator B the OR = 0.8 [95% CI (0.5, 1.3)]. Age and season were confounders: the difference in Campylobacter status between exposed and nonexposed flocks of integrator A could be explained by both variables; for integrator B, only season was associated with Campylobacter status. We found no significant association between partial depopulation and an increased risk of Campylobacter colonization among broiler flocks at final depopulation. This study demonstrates that Campylobacter colonization in a broiler flock is not influenced by the partial depopulation of that flock.

African ancestry, lung function and the effect of genetics

PubMed Central

Wehrmeister, Fernando C.; Hartwig, Fernando P.; Perez-Padilla, Rogelio; Gigante, Denise P.; Barros, Fernando C.; Oliveira, Isabel O.; Ferreira, Gustavo D.; Horta, Bernardo L.

2015-01-01

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. PMID:25700383

Reporting of research quality characteristics of studies published in 6 major clinical dental specialty journals.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Madianos, Phoebus; Makou, Margarita; Eliades, Theodore

2011-06-01

The objective of this article was to record reporting characteristics related to study quality of research published in major specialty dental journals with the highest impact factor (Journal of Endodontics, Journal of Oral and Maxillofacial Surgery, American Journal of Orthodontics and Dentofacial Orthopedics; Pediatric Dentistry, Journal of Clinical Periodontology, and International Journal of Prosthetic Dentistry). The included articles were classified into the following 3 broad subject categories: (1) cross-sectional (snap-shot), (2) observational, and (3) interventional. Multinomial logistic regression was conducted for effect estimation using the journal as the response and randomization, sample calculation, confounding discussed, multivariate analysis, effect measurement, and confidence intervals as the explanatory variables. The results showed that cross-sectional studies were the dominant design (55%), whereas observational investigations accounted for 13%, and interventions/clinical trials for 32%. Reporting on quality characteristics was low for all variables: random allocation (15%), sample size calculation (7%), confounding issues/possible confounders (38%), effect measurements (16%), and multivariate analysis (21%). Eighty-four percent of the published articles reported a statistically significant main finding and only 13% presented confidence intervals. The Journal of Clinical Periodontology showed the highest probability of including quality characteristics in reporting results among all dental journals. Copyright © 2011 Elsevier Inc. All rights reserved.

Testing Confounds to a Developmental Theory of Children's Learning from Television.

ERIC Educational Resources Information Center

Lometti, Guy E.

Children's learning from television was studied in 343 fourth, sixth, seventh, and eighth grade students who viewed an edited version of a television program and took a posttest. It was hypothesized that children would learn more plot-relevant information (central learning material) as they moved from concrete operational to formal operational…

Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.

PubMed

McClanahan, Fabienne; Riches, John C; Miller, Shaun; Day, William P; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M; Capasso, Melania; Gribben, John G

2015-07-09

T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. © 2015 by The American Society of Hematology.

Impact of delay in diagnosis on survival to head and neck carcinomas: a systematic review with meta-analysis.

PubMed

Seoane, J; Takkouche, B; Varela-Centelles, P; Tomás, I; Seoane-Romero, J M

2012-04-01

To address the contradictory information on the role of delay in diagnosis on head and neck cancer survival. Systematic review and meta-analysis. Search on MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011) and ISI proceedings (from inception to March 2011). The terms used were ('Head and neck cancers') AND ('delay'OR'prognostic'OR'survival') both in MeSH terms and free-text words. The reference lists of the retrieved articles were also revised manually to identify other potentially relevant papers. All searches were independently undertaken by two clinicians and one epidemiologist, and the results merged. Primary and specialised care levels. Meta-analysis of data from papers on the subject published from 1966 to 2011. Survival. After search in Medline and other databases, we computed pooled relative risks (RR) and 95% confidence interval (95%CI) from the 10 studies retrieved. The estimate of the relative risk of mortality related to any diagnostic delay (either patient or professional delay) was 1.34 (95%CI 1.12-1.61). Referral delay was associated with a three-fold increase in mortality. Total delay was marginally related to mortality (RR: 1.04, 95%CI: 1.01-1.07). By anatomic location, pharynx cancer shows the highest association (RR: 1.68, 95%CI: 1.22-2.31). Diagnostic delay is a moderate risk factor of mortality from head and neck cancer. However, part of the effect observed may be due to residual confounding (confounding from unknown variables that are not eliminated by adjustment). © 2012 Blackwell Publishing Ltd.

Socioeconomic determinants of disability in Chile.

PubMed

Zitko Melo, Pedro; Cabieses Valdes, Báltica

2011-10-01

Disability is a worldwide public health priority. A shift from a biomedical perspective of dysfunction to a broader social understanding of disability has been proposed. Among many different social factors described in the past, socioeconomic position remains as a key multidimensional determinant of health. The study goal was to analyze the relationship between disability and different domains of socioeconomic position in Chile. Cross-sectional analysis of an anonymized population-based survey conducted in Chile in 2006. Any disability (dichotomous variable) and 6 different types of disability were analyzed on the bases of their relationship with income quintiles, occupational status, educational level, and material living standards (quality of the housing, overcrowding rate and sanitary conditions). Confounding and interaction effects were explored using R statistical program. Income, education, occupation, and material measures of socioeconomic position, along with some sociodemographic characteristics of the population, were independently associated with the chance of being disabled in Chile. Interestingly, classic measures of socioeconomic position (income, education, and occupation) were consistently associated with any disability in Chile, whereas material living conditions were partially confounded by these classic measures. In addition to this, each type of disability showed a particular pattern of related social determinants, which also varied by age group. This study contributed to the understanding of disability in Chile and how different domains of socioeconomic position might be associated with this prevalent condition. Disability remains a complex multidimensional public health problem in Chile that requires the inclusion of a wide range of risk factors, of which socioeconomic position is particularly relevant. Copyright © 2011 Elsevier Inc. All rights reserved.

Mechanisms of PD-L1/PD-1–mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model

PubMed Central

McClanahan, Fabienne; Riches, John C.; Miller, Shaun; Day, William P.; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M.; Capasso, Melania

2015-01-01

T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3+CD8+ T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1+ T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8+ T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. PMID:25979947

Effects of various factors on Doppler ultrasonographic measurements of radial and coccygeal arterial blood pressure in privately owned, conscious cats.

PubMed

Whittemore, Jacqueline C; Nystrom, Michael R; Mawby, Dianne I

2017-04-01

OBJECTIVE To assess the effects of age, body condition score (BCS), and muscle condition score (MCS) on radial and coccygeal systolic arterial blood pressure (SAP) in cats. DESIGN Prospective randomized trial. ANIMALS 66 privately owned cats enrolled between May and December 2010. PROCEDURES BCS and MCS of cats were assessed by 2 investigators; SAP was measured via Doppler ultrasonic flow detector, with cats positioned in right lateral or sternal recumbency for measurements at the radial or coccygeal artery, respectively, with order of site randomized. Associations among variables were assessed through correlation coefficients, partial correlation coefficients, and ANCOVA. RESULTS Interrater reliability for BCS and MCS assessment was high (correlation coefficients, 0.95 and 0.83, respectively). No significant effect was identified for order of SAP measurement sites. Coccygeal and radial SAP were positively correlated (ρ = 0.45). The median difference in coccygeal versus radial SAP was 19 mm Hg, but differences were not consistently positive or negative. Radial SAP was positively correlated with age (ρ = 0.48) and negatively correlated with MCS (ρ = -0.30). On the basis of the correlation analysis, the association between radial SAP and MCS reflected the confounding influence of age. Coccygeal SAP was not significantly correlated with age, BCS, or MCS. CONCLUSIONS AND CLINICAL RELEVANCE Use of the coccygeal artery is recommended to reduce the confounding effects of age and sarcopenia on Doppler ultrasonographic SAP measurements in cats. Additionally, monitoring for changes in MCS is recommended for cats undergoing serial SAP measurement.

Impact of Antiretroviral Treatment Containing Tenofovir Difumarate on the Telomere Length of Aviremic HIV-Infected Patients.

PubMed

Montejano, Rocio; Stella-Ascariz, Natalia; Monge, Susana; Bernardino, José I; Pérez-Valero, Ignacio; Montes, María L; Valencia, Eulalia; Martín-Carbonero, Luz; Moreno, Victoria; González-García, Juan; Arnalich, Francisco; Mingorance, Jesús; Pintado Berniches, Laura; Perona, Rosario; Arribas, José R

2017-09-01

To evaluate the in vivo relevance of the inhibitory effect of tenofovir on telomerase activity observed in vitro. Cross-sectional study of HIV-infected patients with suppressed virological replication (HIV RNA <50 copies/mL for more than 1 year). Telomere length in whole blood was measured by quantitative real-time polymerase chain reaction. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders. 200 patients included, 72% men, median age 49 (IQR 45-54.5), 103 with exposure to a TDF containing antiretroviral treatment (ART) regimen (69.9% for more than 5 years) and 97 never exposed to a TDF containing ART regimen. In the multivariate analysis, significant predictors of shorter telomere length were older age (P = 0.008), parental age at birth (P = 0.038), white race (P = 0.048), and longer time of known HIV infection (10-20 and ≥20 years compared with <10 years, P = 0.003 and P = 0.056, respectively). There was no association between TDF exposure and telomere length after adjusting for possible confounding factors (age, parental age at birth, race, and time of HIV infection). Total time receiving ART and duration of treatment with nucleoside reverse transcriptase inhibitors were associated with shorter telomere length, but these associations were explained by time of known HIV infection. Our data do not suggest that telomerase activity inhibition caused by TDF in vitro leads to telomere shortening in peripheral blood of HIV-infected patients.

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

'Mechanical restraint-confounders, risk, alliance score': testing the clinical validity of a new risk assessment instrument.

PubMed

Deichmann Nielsen, Lea; Bech, Per; Hounsgaard, Lise; Alkier Gildberg, Frederik

2017-08-01

Unstructured risk assessment, as well as confounders (underlying reasons for the patient's risk behaviour and alliance), risk behaviour, and parameters of alliance, have been identified as factors that prolong the duration of mechanical restraint among forensic mental health inpatients. To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint-Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient's readiness to be released from mechanical restraint. The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. The three sub-scales (Confounders, Risk, and a parameter of Alliance) showed excellent content validity. The clinical validations also showed that MR-CRAS was perceived and experienced as a comprehensible, relevant, comprehensive, and useable risk assessment instrument. MR-CRAS contains 18 clinically valid items, and the instrument can be used to support the clinical decision-making regarding the possibility of releasing the patient from mechanical restraint. The present three studies have clinically validated a short MR-CRAS scale that is currently being psychometrically tested in a larger study.

Confounding Problems in Multifactor AOV When Using Several Organismic Variables of Limited Reliability

ERIC Educational Resources Information Center

Games, Paul A.

1975-01-01

A brief introduction is presented on how multiple regression and linear model techniques can handle data analysis situations that most educators and psychologists think of as appropriate for analysis of variance. (Author/BJG)

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.

A comparison of estimators from self-controlled case series, case-crossover design, and sequence symmetry analysis for pharmacoepidemiological studies.

PubMed

Takeuchi, Yoshinori; Shinozaki, Tomohiro; Matsuyama, Yutaka

2018-01-08

Despite the frequent use of self-controlled methods in pharmacoepidemiological studies, the factors that may bias the estimates from these methods have not been adequately compared in real-world settings. Here, we comparatively examined the impact of a time-varying confounder and its interactions with time-invariant confounders, time trends in exposures and events, restrictions, and misspecification of risk period durations on the estimators from three self-controlled methods. This study analyzed self-controlled case series (SCCS), case-crossover (CCO) design, and sequence symmetry analysis (SSA) using simulated and actual electronic medical records datasets. We evaluated the performance of the three self-controlled methods in simulated cohorts for the following scenarios: 1) time-invariant confounding with interactions between the confounders, 2) time-invariant and time-varying confounding without interactions, 3) time-invariant and time-varying confounding with interactions among the confounders, 4) time trends in exposures and events, 5) restricted follow-up time based on event occurrence, and 6) patient restriction based on event history. The sensitivity of the estimators to misspecified risk period durations was also evaluated. As a case study, we applied these methods to evaluate the risk of macrolides on liver injury using electronic medical records. In the simulation analysis, time-varying confounding produced bias in the SCCS and CCO design estimates, which aggravated in the presence of interactions between the time-invariant and time-varying confounders. The SCCS estimates were biased by time trends in both exposures and events. Erroneously short risk periods introduced bias to the CCO design estimate, whereas erroneously long risk periods introduced bias to the estimates of all three methods. Restricting the follow-up time led to severe bias in the SSA estimates. The SCCS estimates were sensitive to patient restriction. The case study showed that although macrolide use was significantly associated with increased liver injury occurrence in all methods, the value of the estimates varied. The estimations of the three self-controlled methods depended on various underlying assumptions, and the violation of these assumptions may cause non-negligible bias in the resulting estimates. Pharmacoepidemiologists should select the appropriate self-controlled method based on how well the relevant key assumptions are satisfied with respect to the available data.

Understanding logistic regression analysis.

PubMed

Sperandei, Sandro

2014-01-01

Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed.

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 Bayesian Framework to Account for Complex Non-Genetic Factors in Gene Expression Levels Greatly Increases Power in eQTL Studies

PubMed Central

Durbin, Richard; Winn, John

2010-01-01

Gene expression measurements are influenced by a wide range of factors, such as the state of the cell, experimental conditions and variants in the sequence of regulatory regions. To understand the effect of a variable of interest, such as the genotype of a locus, it is important to account for variation that is due to confounding causes. Here, we present VBQTL, a probabilistic approach for mapping expression quantitative trait loci (eQTLs) that jointly models contributions from genotype as well as known and hidden confounding factors. VBQTL is implemented within an efficient and flexible inference framework, making it fast and tractable on large-scale problems. We compare the performance of VBQTL with alternative methods for dealing with confounding variability on eQTL mapping datasets from simulations, yeast, mouse, and human. Employing Bayesian complexity control and joint modelling is shown to result in more precise estimates of the contribution of different confounding factors resulting in additional associations to measured transcript levels compared to alternative approaches. We present a threefold larger collection of cis eQTLs than previously found in a whole-genome eQTL scan of an outbred human population. Altogether, 27% of the tested probes show a significant genetic association in cis, and we validate that the additional eQTLs are likely to be real by replicating them in different sets of individuals. Our method is the next step in the analysis of high-dimensional phenotype data, and its application has revealed insights into genetic regulation of gene expression by demonstrating more abundant cis-acting eQTLs in human than previously shown. Our software is freely available online at http://www.sanger.ac.uk/resources/software/peer/. PMID:20463871

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.

Machine Learning Approaches to Increasing Value of Spaceflight Omics Databases

NASA Technical Reports Server (NTRS)

Gentry, Diana

2017-01-01

The number of spaceflight bioscience mission opportunities is too small to allow all relevant biological and environmental parameters to be experimentally identified. Simulated spaceflight experiments in ground-based facilities (GBFs), such as clinostats, are each suitable only for particular investigations -- a rotating-wall vessel may be 'simulated microgravity' for cell differentiation (hours), but not DNA repair (seconds) -- and introduce confounding stimuli, such as motor vibration and fluid shear effects. This uncertainty over which biological mechanisms respond to a given form of simulated space radiation or gravity, as well as its side effects, limits our ability to baseline spaceflight data and validate mission science. Machine learning techniques autonomously identify relevant and interdependent factors in a data set given the set of desired metrics to be evaluated: to automatically identify related studies, compare data from related studies, or determine linkages between types of data in the same study. System-of-systems (SoS) machine learning models have the ability to deal with both sparse and heterogeneous data, such as that provided by the small and diverse number of space biosciences flight missions; however, they require appropriate user-defined metrics for any given data set. Although machine learning in bioinformatics is rapidly expanding, the need to combine spaceflight/GBF mission parameters with omics data is unique. This work characterizes the basic requirements for implementing the SoS approach through the System Map (SM) technique, a composite of a dynamic Bayesian network and Gaussian mixture model, in real-world repositories such as the GeneLab Data System and Life Sciences Data Archive. The three primary steps are metadata management for experimental description using open-source ontologies, defining similarity and consistency metrics, and generating testing and validation data sets. Such approaches to spaceflight and GBF omics data may soon enable unique insight into which measured phenomena correlate to biological mechanisms that are truly affected by spaceflight conditions; which are most likely to be confounded by other variables; and which are insufficiently characterized, significantly increasing existing and future science return from ISS and spaceflight missions.

The relationship of bone and blood lead to hypertension: Further analyses of the normative aging study data

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

Hu, H.; Kim, Rokho; Korrick, S.

1996-12-31

In an earlier report based on participants in the Veterans Administration Normative Aging Study, we found a significant association between the risk of hypertension and lead levels in tibia. To examine the possible confounding effects of education and occupation, we considered in this study five levels of education and three levels of occupation as independent variables in the statistical model. Of 1,171 active subjects seen between August 1991 and December 1994, 563 provided complete data for this analysis. In the initial logistic regression model, acre and body mass index, family history of hypertension, and dietary sodium intake, but neither cumulativemore » smoking nor alcohol ingestion, conferred increased odds ratios for being hypertensive that were statistically significant. When the lead biomarkers were added separately to this initial logistic model, tibia lead and patella lead levels were associated with significantly elevated odds ratios for hypertension. In the final backward elimination logistic regression model that included categorical variables for education and occupation, the only variables retained were body mass index, family history of hypertension, and tibia lead level. We conclude that education and occupation variables were not confounding the association between the lead biomarkers and hypertension that we reported previously. 27 refs., 3 tabs.« less

Suicide and occupation: further supportive evidence for their relevance.

PubMed

Nishimura, Mariko; Terao, Takeshi; Soeda, Shuji; Nakamura, Jun; Iwata, Noboru; Sakamoto, Kaoru

2004-01-01

In recent years, the relationship between occupation and suicide has been extensively investigated, but few definite conclusions regarding the nature of the relationship have been established. In the present study, this relationship was investigated by examining Japanese governmental statistics. First, correlations of suicide rate relative to industry categories were examined individually for primary industry (farmers, fishermen, and forest workers), secondary industry (construction workers, manufacture works, and miners), and tertiary industry (indoor workers) for all of the 47 prefectures of Japan. Second, in the industries that showed a significant correlation with suicide rate, the relationship to other factors was adjusted using possibly confounding factors. As a result, suicide rate was positively correlated with primary industry percentage, but not with secondary or tertiary industry percentages. Multiple regression analysis showed that suicide rate was positively associated with primary industry percentage with significant tendency while it was significantly and negatively associated with annual total sunshine. Limitations are that individual suicide rates according to occupational types were not available and direct correlations with the above variables could not be investigated. The present findings suggest a possibility that occupational factors associated with primary industry may be relevant to suicide, and that, additionally, annual total sunshine may affect suicide independently. Since workers with primary industry are likely to be exposed to sunshine than other workers, they may tend to be more affected by the decrease of annual total sunshine.

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

Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adult patients

PubMed Central

de Winter, Brenda C. M.; Masman, Anniek D.; van Dijk, Monique; Baar, Frans P. M.; Tibboel, Dick; Koch, Birgit C. P.; van Gelder, Teun; Mathot, Ron A. A.

2017-01-01

Aims Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status. The goal of this study was to combine this PK information with pharmacodynamic (PD) data, to evaluate the variability in response to midazolam and to find clinically relevant covariates that may predict PD response. Method A population PD analysis using nonlinear mixed effect models was performed with data from 43 terminally ill patients. PK profiles were predicted by a previously described PK model and depth of sedation was measured using the Ramsay sedation score. Patient and disease characteristics were evaluated as possible covariates. The final model was evaluated using a visual predictive check. Results The effect of midazolam on the sedation level was best described by a differential odds model including a baseline probability, Emax model and interindividual variability on the overall effect. The EC50 value was 68.7 μg l–1 for a Ramsay score of 3–5 and 117.1 μg l–1 for a Ramsay score of 6. Comedication with haloperidol was the only significant covariate. The visual predictive check of the final model showed good model predictability. Conclusion We were able to describe the clinical response to midazolam accurately. As expected, there was large variability in response to midazolam. The use of haloperidol was associated with a lower probability of sedation. This may be a result of confounding by indication, as haloperidol was used to treat delirium, and deliria has been linked to a more difficult sedation procedure. PMID:28960387

Frailty among rural elderly adults

PubMed Central

2014-01-01

Background This study aimed to estimate the prevalence and associated factors related to frailty, by Fried criteria, in the elderly population in a rural area in the Andes Mountains, and to analyze the relationship of these with comorbidity and disability. Methods A cross-sectional study was undertaken involving 1878 participants 60 years of age and older. The frailty syndrome was diagnosed based on the Fried criteria (weakness, low speed, low physical activity, exhaustion, and weight loss). Variables were grouped as theoretical domains and, along with other potential confounders, were placed into five categories: (a) demographic and socioeconomic status, (b) health status, (c) self-reported functional status, (d) physical performance-based measures, and (e) psychosocial factors. Chi-square, ANOVA, and multinomial logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest. Results The prevalence of frailty was 12.2%. Factors associated with frailty were age, gender, health status variables that included self-perceived health and number of chronic conditions, functional covariate variables that included disability in activities in daily living (ADL), disabilities in instrumental ADL, chair stand time, and psychosocial variables that included depressive symptoms and cognitive impairment. Higher comorbidity and disability was found in frail elderly people. Only a subset of frail elderly people (10%) reported no disease or disability. Conclusions A relevant number of elderly persons living in rural areas in the Andes Mountains are frail. The prevalence of frailty is similar to that reported in other populations in the Latin American region. Our results support the use of modified Cardiovascular Health Study criteria to measure frailty in communities other than urban settings. Frailty in this study was strongly associated with comorbidities, and frailty and comorbidity predicted disability. PMID:24405584

COMPOSITE SAMPLING FOR SOIL VOC ANALYSIS

EPA Science Inventory

Data published by numerous researchers over the last decade demonstrate that there is a high degree of spatial variability in the measurement of volatile organic compounds (VOCs) in soil at contaminated waste sites. This phenomenon is confounded by the use of a small sample aliqu...

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

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.

A long term study of pulmonary function among US refractory ceramic fibre workers

PubMed Central

LeMasters, Grace K; Hilbert, Timothy J; Levin, Linda S; Rice, Carol H; Borton, Eric K; Lockey, James E

2010-01-01

Background Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. Methods Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. Results Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. Conclusion No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described. PMID:20798015

Alcohol Use in Adolescence and Later Working Memory: Findings From a Large Population-Based Birth Cohort

PubMed Central

Field, Matt; Gage, Suzanne; Hammerton, Gemma; Heron, Jon; Hickman, Matt; Munafò, Marcus R

2018-01-01

Abstract Aims The study aimed to examine the association between adolescent alcohol use and working memory (WM) using a large population sample. Methods Data from the Avon Longitudinal Study of Parents and Children were used to investigate the association between alcohol use at age 15 years and WM 3 years later, assessed using the N-back task (N ~ 3300). A three-category ordinal variable captured mutually exclusive alcohol groupings ranging in order of severity (i.e. low alcohol users, frequent drinkers and frequent/binge drinkers). Differential dropout was accounted for using multiple imputation and inverse probability weighting. Adjustment was made for potential confounders. Results There was evidence of an association between frequent/binge drinking (compared to the low alcohol group) and poorer performance on the 3-back task after adjusting for sociodemographic confounding variables, WM at age 11 years, and experience of a head injury/unconsciousness before age 11 years (β = −0.23, 95% CI = −0.37 to −0.09, P = 0.001). However, this association was attenuated (β = −0.12, 95% CI = −0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly cigarette tobacco and cannabis use. Weaker associations were found for the less demanding 2-back task. We found no evidence to suggest frequent drinking was associated with performance on either task. Conclusions We found weak evidence of an association between sustained heavy alcohol use in mid-adolescence and impaired WM 3 years later. Although we cannot fully rule out the possibility of reverse causation, several potential confounding variables were included to address the directionality of the relationship between WM and alcohol use problems. PMID:29329371

Alcohol Use in Adolescence and Later Working Memory: Findings From a Large Population-Based Birth Cohort.

PubMed

Mahedy, Liam; Field, Matt; Gage, Suzanne; Hammerton, Gemma; Heron, Jon; Hickman, Matt; Munafò, Marcus R

2018-05-01

The study aimed to examine the association between adolescent alcohol use and working memory (WM) using a large population sample. Data from the Avon Longitudinal Study of Parents and Children were used to investigate the association between alcohol use at age 15 years and WM 3 years later, assessed using the N-back task (N ~ 3300). A three-category ordinal variable captured mutually exclusive alcohol groupings ranging in order of severity (i.e. low alcohol users, frequent drinkers and frequent/binge drinkers). Differential dropout was accounted for using multiple imputation and inverse probability weighting. Adjustment was made for potential confounders. There was evidence of an association between frequent/binge drinking (compared to the low alcohol group) and poorer performance on the 3-back task after adjusting for sociodemographic confounding variables, WM at age 11 years, and experience of a head injury/unconsciousness before age 11 years (β = -0.23, 95% CI = -0.37 to -0.09, P = 0.001). However, this association was attenuated (β = -0.12, 95% CI = -0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly cigarette tobacco and cannabis use. Weaker associations were found for the less demanding 2-back task. We found no evidence to suggest frequent drinking was associated with performance on either task. We found weak evidence of an association between sustained heavy alcohol use in mid-adolescence and impaired WM 3 years later. Although we cannot fully rule out the possibility of reverse causation, several potential confounding variables were included to address the directionality of the relationship between WM and alcohol use problems.

Pregnant women with the sickle cell trait are not at increased risk for developing preeclampsia.

PubMed

Stamilio, David M; Sehdev, Harish M; Macones, George A

2003-01-01

The primary objective of this study was to determine whether having the sickle cell trait is independently associated with preeclampsia. We performed a retrospective cohort study of 1998 pregnant patients who either did or did not have the sickle cell trait. All patients were screened for the sickle trait using the "Sickledex" test. Data on neonatal and maternal outcome, including preeclampsia, and potential confounding variables were abstracted from medical records. Unadjusted, stratified, and multiple logistic regression analyses were used to identify interactions, and confounding between multiple variables and the association between sickle cell trait and preeclampsia. With an anticipated 6.5% rate of preeclampsia, and alpha = 0.05, this cohort study has 80% power to detect a relative risk (RR) of 2.3 for preeclampsia. Univariate analysis revealed that the two cohorts were similar with regard to primiparity, maternal age, chronic diseases, birth weight, and gestational age at delivery, but the sickle cell trait cohort was more likely to have gestational diabetes and had a higher mean body mass index (BMI). In the univariate analysis, the sickle cell trait cohort was not at increased risk for preeclampsia [unadjusted RR = 0.5, 95% CI (0.2-1.6)]. After controlling for potential confounding variables with logistic regression analysis, sickle trait was not independently associated with preeclampsia [adjusted RR = 0.5, 95% CI (0.2- 1.6)]. In contrast to prior work, these data suggest that the sickle cell trait is not an independent risk factor for preeclampsia or postpartum complications. In fact, the data are more consistent with the sickle trait being protective for developing preeclampsia.

College quality and hourly wages: evidence from the self-revelation model, sibling models and instrumental variables.

PubMed

Borgen, Nicolai T

2014-11-01

This paper addresses the recent discussion on confounding in the returns to college quality literature using the Norwegian case. The main advantage of studying Norway is the quality of the data. Norwegian administrative data provide information on college applications, family relations and a rich set of control variables for all Norwegian citizens applying to college between 1997 and 2004 (N = 141,319) and their succeeding wages between 2003 and 2010 (676,079 person-year observations). With these data, this paper uses a subset of the models that have rendered mixed findings in the literature in order to investigate to what extent confounding biases the returns to college quality. I compare estimates obtained using standard regression models to estimates obtained using the self-revelation model of Dale and Krueger (2002), a sibling fixed effects model and the instrumental variable model used by Long (2008). Using these methods, I consistently find increasing returns to college quality over the course of students' work careers, with positive returns only later in students' work careers. I conclude that the standard regression estimate provides a reasonable estimate of the returns to college quality. Copyright © 2014 Elsevier Inc. All rights reserved.

Detectability and Interpretational Uncertainties: Considerations in Gauging the Impacts of Land Disturbance on Streamflow

EPA Science Inventory

Hydrologic impacts of land disturbance and management can be confounded by rainfall variability. As a consequence, attempts to gauge and quantify these effects through streamflow monitoring are typically subject to uncertainties. This paper addresses the quantification and deline...

Supportive Family Environments Ameliorate the Link Between Racial Discrimination and Epigenetic Aging: A Replication Across Two Longitudinal Cohorts.

PubMed

Brody, Gene H; Miller, Gregory E; Yu, Tianyi; Beach, Steven R H; Chen, Edith

2016-04-01

This study tested the hypothesis that supportive family environments during adolescence buffer exposure to racial discrimination, reducing its impact on biological weathering and its manifestation in cellular aging. Perceived racial discrimination, support in the family environment, and confounder variables were assessed for 3 consecutive years across adolescence in two independent cohorts of African American youth from rural Georgia. DNA was extracted from peripheral blood mononuclear cells collected during young adulthood. Patterns of methylation were used to index the epigenetic ages of these cells and the extent to which they differed from participants' chronological ages. Among youth in supportive family environments, exposure to higher levels of racial discrimination did not forecast greater epigenetic aging. Among youth in less supportive family environments, exposure to higher levels of racial discrimination did forecast greater epigenetic aging. The associations emerged independently of confounder variables, and the results were replicated across the two cohorts. © The Author(s) 2016.

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

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

Socio-environmental predictors of Barmah forest virus transmission in coastal areas, Queensland, Australia.

PubMed

Naish, Suchithra; Hu, Wenbiao; Nicholls, Neville; Mackenzie, John S; Dale, Pat; McMichael, Anthony J; Tong, Shilu

2009-02-01

To assess the socio-environmental predictors of Barmah forest virus (BFV) transmission in coastal areas, Queensland, Australia. Data on BFV notified cases, climate, tidal levels and socioeconomic index for area (SEIFA) in six coastal cities, Queensland, for the period 1992-2001 were obtained from the relevant government agencies. Negative binomial regression models were used to assess the socio-environmental predictors of BFV transmission. The results show that maximum and minimum temperature, rainfall, relative humidity, high and low tide were statistically significantly associated with BFV incidence at lags 0-2 months. The fitted negative binomial regression models indicate a significant independent association of each of maximum temperature (beta = 0.139, P = 0.000), high tide (beta = 0.005, P = 0.000) and SEIFA index (beta = -0.010, P = 0.000) with BFV transmission after adjustment for confounding variables. The transmission of BFV disease in Queensland coastal areas seemed to be determined by a combination of local social and environmental factors. The model developed in this study may have applications in the control and prevention of BFV disease in these areas.

Discriminability effect on Garner interference: evidence from recognition of facial identity and expression

PubMed Central

Wang, Yamin; Fu, Xiaolan; Johnston, Robert A.; Yan, Zheng

2013-01-01

Using Garner’s speeded classification task existing studies demonstrated an asymmetric interference in the recognition of facial identity and facial expression. It seems that expression is hard to interfere with identity recognition. However, discriminability of identity and expression, a potential confounding variable, had not been carefully examined in existing studies. In current work, we manipulated discriminability of identity and expression by matching facial shape (long or round) in identity and matching mouth (opened or closed) in facial expression. Garner interference was found either from identity to expression (Experiment 1) or from expression to identity (Experiment 2). Interference was also found in both directions (Experiment 3) or in neither direction (Experiment 4). The results support that Garner interference tends to occur under condition of low discriminability of relevant dimension regardless of facial property. Our findings indicate that Garner interference is not necessarily related to interdependent processing in recognition of facial identity and expression. The findings also suggest that discriminability as a mediating factor should be carefully controlled in future research. PMID:24391609

Morning blood pressure surge: pathophysiology, clinical relevance and therapeutic aspects

PubMed Central

Bilo, Grzegorz; Grillo, Andrea; Guida, Valentina; Parati, Gianfranco

2018-01-01

Morning hours are the period of the day characterized by the highest incidence of major cardiovascular events including myocardial infarction, sudden death or stroke. They are also characterized by important neurohormonal changes, in particular, the activation of sympathetic nervous system which usually leads to a rapid increase in blood pressure (BP), known as morning blood pressure surge (MBPS). It was hypothesized that excessive MBPS may be causally involved in the pathogenesis of cardiovascular events occurring in the morning by inducing hemodynamic stress. A number of studies support an independent relationship of MBPS with organ damage, cerebrovascular complications and mortality, although some heterogeneity exists in the available evidence. This may be due to ethnic differences, methodological issues and the confounding relationship of MBPS with other features of 24-hour BP profile, such as nocturnal dipping or BP variability. Several studies are also available dealing with treatment effects on MBPS and indicating the importance of long-acting antihypertensive drugs in this regard. This paper provides an overview of pathophysiologic, methodological, prognostic and therapeutic aspects related to MBPS. PMID:29872338

Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium.

PubMed

Hermann, B P; Trenerry, M R; Colligan, R C

1996-07-01

We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.

Lack of Breastfeeding: A Potential Risk Factor in the Multifactorial Genesis of Borderline Personality Disorder and Impaired Maternal Bonding.

PubMed

Schwarze, Cornelia E; Hellhammer, Dirk H; Stroehle, Verena; Lieb, Klaus; Mobascher, Arian

2015-10-01

Borderline personality disorder (BPD) is characterized by a pattern of intense but unstable interpersonal relationships. These interpersonal dysfunctions may originate from impaired bonding and attachment that is determined during early life. Remarkably, it has been reported that the quality of mother-infant relationship is influenced by the feeding mode. Thus, bottle feeding instead of breastfeeding and possible lack of maternal bonding-related behavior may increase the risk for later psychopathology and attachment problems as seen in BPD. A total of 100 BPD patients and 100 matched healthy controls underwent semistructured interviews, based on retrospective information about early risk factors and breastfeeding during infancy. The authors' analyses revealed that BPD patients were significantly less breastfed compared to healthy controls (no breastfeeding in BPD: 42.4%; no breastfeeding in controls: 18.2%; p < .001). The BPD diagnosis was significantly predicted by the variable "no breastfeeding" (p < .001; odds ratio [OR] = 3.32; confidence interval [CI] [1.74, 6.34]), even after adjustment for childhood trauma and several confounding factors (p = .001). The variable "no breastfeeding" accounts for 9.1% of the variance of the BPD diagnosis and is associated with low perceived maternal bonding (p = .006). Breastfeeding may act as an early indicator of the mother-infant relationship that seems to be relevant for bonding and attachment later in life.

Elder abuse and its medical outcomes in older Chinese people with cognitive and physical impairments.

PubMed

Fang, Boye; Yan, Elsie; Chan, Ko Ling; Ip, Partick

2018-05-04

Elder abuse poses a major public health threat considering the ongoing rapid aging of the global population. This study investigates the association between elder abuse by family caregivers and medical outcomes among older Chinese patients with cognitive and physical impairments in the People's Republic of China. Using cross-sectional design, 1002 older patients (aged 55 y and older) and their family caregivers were recruited from 3 grade A hospitals in Guangdong Province. The major independent variable is caregiver-reported elder abuse, while outcome variables include cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, peptic ulcer, digestive disorder, chronic hepatic disease, chronic renal disease, metabolic disease, acute inflammation, joint disease, tumor, and general injury. The prevalence of these medical conditions among patients who were abused and those who were not were compared using descriptive analyses and chi-square tests, and logistic regression was used to establish the relevant independent associations. A total of 429 (42.8%) older persons have experienced physical or psychological abuse over the past 12 months. After adjusting for potential confounders, abused older persons were more susceptible to cardiovascular disease, chronic obstructive pulmonary disease, peptic ulcer, digestive disorder, metabolic disease, acute inflammation, tumor, and injuries. Elder abuse is associated with various major medical morbidities. Interdisciplinary cooperation is necessary to identify and reduce the adverse physiological consequences in victims. Copyright © 2018 John Wiley & Sons, Ltd.

Beyond logistic regression: structural equations modelling for binary variables and its application to investigating unobserved confounders.

PubMed

Kupek, Emil

2006-03-15

Structural equation modelling (SEM) has been increasingly used in medical statistics for solving a system of related regression equations. However, a great obstacle for its wider use has been its difficulty in handling categorical variables within the framework of generalised linear models. A large data set with a known structure among two related outcomes and three independent variables was generated to investigate the use of Yule's transformation of odds ratio (OR) into Q-metric by (OR-1)/(OR+1) to approximate Pearson's correlation coefficients between binary variables whose covariance structure can be further analysed by SEM. Percent of correctly classified events and non-events was compared with the classification obtained by logistic regression. The performance of SEM based on Q-metric was also checked on a small (N = 100) random sample of the data generated and on a real data set. SEM successfully recovered the generated model structure. SEM of real data suggested a significant influence of a latent confounding variable which would have not been detectable by standard logistic regression. SEM classification performance was broadly similar to that of the logistic regression. The analysis of binary data can be greatly enhanced by Yule's transformation of odds ratios into estimated correlation matrix that can be further analysed by SEM. The interpretation of results is aided by expressing them as odds ratios which are the most frequently used measure of effect in medical statistics.

Job Strain and the Cortisol Diurnal Cycle in MESA: Accounting for Between- and Within-Day Variability.

PubMed

Rudolph, Kara E; Sánchez, Brisa N; Stuart, Elizabeth A; Greenberg, Benjamin; Fujishiro, Kaori; Wand, Gary S; Shrager, Sandi; Seeman, Teresa; Diez Roux, Ana V; Golden, Sherita H

2016-03-01

Evidence of the link between job strain and cortisol levels has been inconsistent. This could be due to failure to account for cortisol variability leading to underestimated standard errors. Our objective was to model the relationship between job strain and the whole cortisol curve, accounting for sources of cortisol variability. Our functional mixed-model approach incorporated all available data-18 samples over 3 days-and uncertainty in estimated relationships. We used employed participants from the Multi-Ethnic Study of Atherosclerosis Stress I Study and data collected between 2002 and 2006. We used propensity score matching on an extensive set of variables to control for sources of confounding. We found that job strain was associated with lower salivary cortisol levels and lower total area under the curve. We found no relationship between job strain and the cortisol awakening response. Our findings differed from those of several previous studies. It is plausible that our results were unique to middle- to older-aged racially, ethnically, and occupationally diverse adults and were therefore not inconsistent with previous research among younger, mostly white samples. However, it is also plausible that previous findings were influenced by residual confounding and failure to propagate uncertainty (i.e., account for the multiple sources of variability) in estimating cortisol features. © 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.

Wavelet-based functional linear mixed models: an application to measurement error-corrected distributed lag models.

PubMed

Malloy, Elizabeth J; Morris, Jeffrey S; Adar, Sara D; Suh, Helen; Gold, Diane R; Coull, Brent A

2010-07-01

Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient is necessary for estimation. Additional issues in this setting are the possibility of exposure measurement error and the need to incorporate additional potential confounders, such as meteorological or co-pollutant measures, that themselves may have effects that vary over time. To accommodate all these features, we develop wavelet-based linear mixed distributed lag models that incorporate repeated measures of functional data as covariates into a linear mixed model. A Bayesian approach to model fitting uses wavelet shrinkage to regularize functional coefficients. We show that, as long as the exposure error induces fine-scale variability in the functional exposure profile and the distributed lag function representing the exposure effect varies smoothly in time, the model corrects for the exposure measurement error without further adjustment. Both these conditions are likely to hold in the environmental applications we consider. We examine properties of the method using simulations and apply the method to data from a study examining the association between PM, measured as hourly averages for 1-7 days, and markers of acute systemic inflammation. We use the method to fully control for the effects of confounding by other time-varying predictors, such as temperature and co-pollutants.

Impact of proteinuria and glomerular filtration rate on risk of ischaemic and intracerebral hemorrhagic stroke: a result from the Kailuan study.

PubMed

Li, Z; Wang, A; Cai, J; Gao, X; Zhou, Y; Luo, Y; Wu, S; Zhao, X

2015-02-01

Persons with chronic kidney disease, defined by a reduced estimated glomerular filtration rate and proteinuria, have an increased risk of cardiovascular disease including stroke. However, data from developing countries are limited. Our aim was to assess the relationship between chronic kidney disease and risk of stroke and its subtypes in a community-based population in China. The study was based on 92,013 participants (18-98 years old; 73,248 men and 18,765 women) of the Kailuan study who at baseline were free from stroke and myocardial infarction and had undergone tests for serum creatinine or proteinuria. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration formula and proteinuria by the urine dipstick result in laboratory databases. The primary outcome was the first occurrence of stroke. Data were analyzed using Cox proportional hazards models adjusted for relevant confounders and results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). During a follow-up of 4 years, 1575 stroke events (1128 ischaemic, 406 intracerebral hemorrhagic and 41 subarachnoid hemorrhagic strokes) occurred. After adjustment for variable confounders, patients with proteinuria were found to have increased HRs for the total and subtypes of stroke events (HR 1.61; 95% CI 1.35-1.92 for total stroke; HR 1.53; 95% CI 1.24-1.89 for ischaemic stroke; and HR 1.90; 95% CI 1.35-2.67 for hemorrhagic stroke). However, estimated glomerular filtration rate was not associated with incident stroke after adjustment for established cardiovascular risk factors. Proteinuria increased the risk of stroke in a general Chinese population. © 2014 EAN.

Prenatal diet and children's trajectories of hyperactivity-inattention and conduct problems from 3 to 8 years: the EDEN mother-child cohort.

PubMed

Galera, Cédric; Heude, Barbara; Forhan, Anne; Bernard, Jonathan Y; Peyre, Hugo; Van der Waerden, Judith; Pryor, Laura; Bouvard, Manuel-Pierre; Melchior, Maria; Lioret, Sandrine; de Lauzon-Guillain, Blandine

2018-03-24

Evidence shows that diet contributes substantially to lifelong physical and mental health. Although dietary exposure during gestation and early postnatal life is critical, human epidemiological data are limited regarding its link with children's subsequent externalizing issues. The aim of this study was to investigate the role of maternal diet during pregnancy in offspring's symptoms of hyperactivity-inattention and conduct problems from ages 3 to 8 years. We used data of 1,242 mother-child pairs from a French cohort followed up from pregnancy until the children were 8 years of age. Dietary patterns (DP) of the mother during pregnancy were assessed with food frequency questionnaires. Children's externalizing behavior was assessed with the Strength and Difficulties Questionnaire at ages 3, 5, and 8 years, from which trajectories of hyperactivity-inattention symptoms and conduct problems were derived. We conducted multivariable logistic models to study associations adjusted for a range of potential confounders. Results showed significant relationships between maternal 'low Healthy diet' (adjusted Odds Ratio (aOR) = 1.61; IC 95%: 1.09-2.37) and 'high Western diet' (aOR = 1.67; IC 95%: 1.13-2.47) during pregnancy and children's trajectories of high symptoms of hyperactivity-inattention. The associations took into account relevant confounders such as DP of the children at age 2 years, maternal stress and depression, gestational diabetes, and socioeconomic variables. Maternal diet during pregnancy was independently associated with children's hyperactivity-inattention symptoms but not with conduct problems. Early prevention addressing lifestyle should specifically target diet in pregnant women. © 2018 Association for Child and Adolescent Mental Health.

Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia.

PubMed

Gierthmühlen, Janne; Enax-Krumova, Elena K; Attal, Nadine; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Mainka, Tina; Rice, Andrew S C; Segerdahl, Märta; Sindrup, Søren H; Serra, Jordi; Tölle, Thomas; Treede, Rolf-Detlef; Baron, Ralf; Maier, Christoph

2015-11-01

Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.

Safety and efficacy of doxazosin as an "add-on" antihypertensive therapy in mild to moderate heart failure patients.

PubMed

Spoladore, Roberto; Roccaforte, Rosa; Fragasso, Gabriele; Gardini, Chiara; Palloshi, Altin; Cuko, Amarild; Arioli, Francesco; Salerno, Anna; Margonato, Alberto

2009-08-01

Doxazosin treatment has been discouraged in hypertensive patients in order to prevent heart failure (HF) development. However, this drug is still prescribed as an "add-on" medication to achieve a better blood pressure (BP) control. The aim of this study was to evaluate the safety and efficacy of doxazosin as an "add-on" medication in HF patients with uncontrolled hypertension. We reviewed our HF clinic files to collect patient variables recorded at baseline and during follow-up visits in patients receiving, or not, doxazosin. We compared HF-related hospitalization rates and all-cause and cardiovascular mortality rates between patients on doxazosin and those not on doxazosin. We constructed cumulative risk curves for time to first event (HF-related hospitalization and/or death) for both groups of patients. Fifty-two HF patients had been prescribed doxazosin. At baseline, several relevant variables were unevenly distributed between patients receiving doxazosin and those not receiving doxazosin (N=122), such as left ventricular ejection fraction (LVEF) and NYHA class. HF-related hospitalization and death rates were similar between patients on doxazosin and those not on doxazosin at the end of the follow-up. Even after adjustment for all potentially confounding variables, doxazosin was not associated with HF-related hospitalization and/or death. Doxazosin significantly reduced BP, but did not affect NYHA class. Doxazosin, "on top" of other antihypertensive treatments was safe and effective, and did not appear to be associated with HF-related hospitalization and mortality rates in our patients with mild/moderate HF.

Reproductive and developmental effects of disinfection by-products in drinking water.

PubMed Central

Reif, J S; Hatch, M C; Bracken, M; Holmes, L B; Schwetz, B A; Singer, P C

1996-01-01

Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach. PMID:8930546

Plasma free amino acid profiles evaluate risk of metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large Asian population.

PubMed

Yamaguchi, Natsu; Mahbub, M H; Takahashi, Hidekazu; Hase, Ryosuke; Ishimaru, Yasutaka; Sunagawa, Hiroshi; Amano, Hiroki; Kobayashi-Miura, Mikiko; Kanda, Hideyuki; Fujita, Yasuyuki; Yamamoto, Hiroshi; Yamamoto, Mai; Kikuchi, Shinya; Ikeda, Atsuko; Takasu, Mariko; Kageyama, Naoko; Nakamura, Mina; Tanabe, Tsuyoshi

2017-04-07

Recently, the association of plasma free amino acid (PFAA) profile and lifestyle-related diseases has been reported. However, few studies have been reported in large Asian populations, about the usefulness of PFAAs for evaluating disease risks. We examined the ability of PFAA profiles to evaluate lifestyle-related diseases in so far the largest Asian population. We examined plasma concentrations of 19 amino acids in 8589 Japanese subjects, and determined the association with variables associated with obesity, blood glucose, lipid, and blood pressure. We also evaluated the PFAA indexes that reflect visceral fat obesity and insulin resistance. The contribution of single PFAA level and relevant PFAA indexes was also examined in the risk assessment of lifestyle-related diseases. Of the 19 amino acids, branched-chain amino acids and aromatic amino acids showed association with obesity and lipid variables. The PFAA index related to visceral fat obesity showed relatively higher correlation with variables than that of any PFAA. In the evaluation of lifestyle-related disease risks, the odds ratios of the PFAA index related to visceral fat obesity or insulin resistance with the diseases were higher than most of those of individual amino acid levels even after adjusting for potential confounding factors. The association pattern of the indexes and PFAA with each lifestyle-related disease was distinct. We confirmed the usefulness of PFAA profiles and indexes as markers for evaluating the risks of lifestyle-related diseases, including diabetes mellitus, metabolic syndrome, dyslipidemia, and hypertension in a large Asian population.

Primordial and primary prevention programs for cardiovascular diseases: from risk assessment through risk communication to risk reduction. A review of the literature

PubMed Central

Lancarotte, Inês; Nobre, Moacyr Roberto

2016-01-01

The aim of this study was to identify and reflect on the methods employed by studies focusing on intervention programs for the primordial and primary prevention of cardiovascular diseases. The PubMed, EMBASE, SciVerse Hub-Scopus, and Cochrane Library electronic databases were searched using the terms ‘effectiveness AND primary prevention AND risk factors AND cardiovascular diseases’ for systematic reviews, meta-analyses, randomized clinical trials, and controlled clinical trials in the English language. A descriptive analysis of the employed strategies, theories, frameworks, applied activities, and measurement of the variables was conducted. Nineteen primary studies were analyzed. Heterogeneity was observed in the outcome evaluations, not only in the selected domains but also in the indicators used to measure the variables. There was also a predominance of repeated cross-sectional survey design, differences in community settings, and variability related to the randomization unit when randomization was implemented as part of the sample selection criteria; furthermore, particularities related to measures, limitations, and confounding factors were observed. The employed strategies, including their advantages and limitations, and the employed theories and frameworks are discussed, and risk communication, as the key element of the interventions, is emphasized. A methodological process of selecting and presenting the information to be communicated is recommended, and a systematic theoretical perspective to guide the communication of information is advised. The risk assessment concept, its essential elements, and the relevant role of risk perception are highlighted. It is fundamental for communication that statements targeting other people’s understanding be prepared using systematic data. PMID:27982169

Crowding during restricted and free viewing

PubMed Central

Wallace, Julian M.; Chiu, Michael K.; Nandy, Anirvan S.; Tjan, Bosco S.

2013-01-01

Crowding impairs the perception of form in peripheral vision. It is likely to be a key limiting factor of form vision in patients without central vision. Crowding has been extensively studied in normally sighted individuals, typically with a stimulus duration of a few hundred milliseconds to avoid eye movements. These restricted testing conditions do not reflect the natural behavior of a patient with central field loss. Could unlimited stimulus duration and unrestricted eye movements change the properties of crowding in any fundamental way? We studied letter identification in the peripheral vision of normally sighted observers in three conditions: (i) a fixation condition with a brief stimulus presentation of 250 ms, (ii) another fixation condition but with an unlimited viewing time, and (iii) an unrestricted eye movement condition with an artificial central scotoma and an unlimited viewing time. In all conditions, contrast thresholds were measured as a function of target-to-flanker spacing, from which we estimated the spatial extent of crowding in terms of critical spacing. We found that presentation duration beyond 250 ms had little effect on critical spacing with stable gaze. With unrestricted eye movements and a simulated central scotoma, we found a large variability in critical spacing across observers, but more importantly, the variability in critical spacing was well correlated with the variability in target eccentricity. Our results assure that the large body of findings on crowding made with briefly presented stimuli remains relevant to conditions where viewing time is unconstrained. Our results further suggest that impaired oculomotor control associated with central vision loss can confound peripheral form vision beyond the limits imposed by crowding. PMID:23563172

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.

A stratification approach using logit-based models for confounder adjustment in the study of continuous outcomes.

PubMed

Tan, Chuen Seng; Støer, Nathalie C; Chen, Ying; Andersson, Marielle; Ning, Yilin; Wee, Hwee-Lin; Khoo, Eric Yin Hao; Tai, E-Shyong; Kao, Shih Ling; Reilly, Marie

2017-01-01

The control of confounding is an area of extensive epidemiological research, especially in the field of causal inference for observational studies. Matched cohort and case-control study designs are commonly implemented to control for confounding effects without specifying the functional form of the relationship between the outcome and confounders. This paper extends the commonly used regression models in matched designs for binary and survival outcomes (i.e. conditional logistic and stratified Cox proportional hazards) to studies of continuous outcomes through a novel interpretation and application of logit-based regression models from the econometrics and marketing research literature. We compare the performance of the maximum likelihood estimators using simulated data and propose a heuristic argument for obtaining the residuals for model diagnostics. We illustrate our proposed approach with two real data applications. Our simulation studies demonstrate that our stratification approach is robust to model misspecification and that the distribution of the estimated residuals provides a useful diagnostic when the strata are of moderate size. In our applications to real data, we demonstrate that parity and menopausal status are associated with percent mammographic density, and that the mean level and variability of inpatient blood glucose readings vary between medical and surgical wards within a national tertiary hospital. Our work highlights how the same class of regression models, available in most statistical software, can be used to adjust for confounding in the study of binary, time-to-event and continuous outcomes.

Farm-scale variation of soil quality indices and association with edaphic properties

USDA-ARS?s Scientific Manuscript database

Soil organisms are indicators of dynamic soil quality because their community structure and population density are sensitive to management changes. However, edaphic properties can also affect soil organisms and high spatial variability can confound their utility for soil evaluation. In the present...

Microcounseling Skill Discrimination Scale: A Methodological Note

ERIC Educational Resources Information Center

Stokes, Joseph; Romer, Daniel

1977-01-01

Absolute ratings on the Microcounseling Skill Discrimination Scale (MSDS) confound the individual's use of the rating scale and actual ability to discriminate effective and ineffective counselor behaviors. This note suggests methods of scoring the MSDS that will eliminate variability attributable to response language and improve the validity of…

Independent effects and interactions of stand diameter, tree diameter, crown class, and age on tree growth in mixed-species, even-aged hardwood stands

Treesearch

D.A. Marquis

1991-01-01

Many studies have shown that initial tree diameter is closely correlated with subsequent tree growth. But initial tree diameter is actually a confounded variable, incorporating both competitive position (crown class) and age.

Interactions among variants in TXA2R, P2Y12 and GPIIIa are associated with carotid plaque vulnerability in Chinese population.

PubMed

Yi, Xingyang; Lin, Jing; Luo, Hua; Zhou, Ju; Zhou, Qiang; Wang, Yanfen; Wang, Chun

2018-04-03

The associations between variants in platelet activation-relevant genes and carotid plaque vulnerability are not fully understood. The aim of the present study was to investigate the associations of the variants in platelet activation-relevant genes and interactions among these variants with carotid plaque vulnerability. There were no significant differences in the frequencies of genotypes of the 11 variants between patients and controls. Among 396 patients, 102 patients had not carotid plaque, 106 had VP, and 188 had SP. The 11 variants were not independently associated with risk of carotid plaque vulnerability after adjusting for potential confounding variables. However, the GMDR analysis showed that there were synergistic effects of gene-gene interactions among TXA2Rr s1131882, GPIIIa rs2317676 and P2Y12 rs16863323 on carotid plaque vulnerability. The high-risk interactions among the three variants were associated with high platelet activation, and independently associated with the risk of carotid plaque vulnerability. Eleven variants in platelet activation-relevant genes were examined using mass spectrometry methods in 396 ischemic stroke patients and 291controls. Platelet-leukocyte aggregates and platelet aggregation were also measured. Carotid plaques were assessed by B-mode ultrasound. According to the results of ultrasound, the patients were stratified into three groups: non-plaque group, vulnerable plaque (VP) group and stable plaque (SP) group. Furthermore, gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. The rs1131882, rs2317676, and rs16863323 three-loci interactions may confer a higher risk of carotid plaque vulnerability, and might be potential markers for plaque instability.

Antidepressants and testicular cancer: cause versus association.

PubMed

Andrade, Chittaranjan

2014-03-01

A data mining study that examined associations between 105 drugs and 55 cancer sites found significant associations between 2 selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and testicular cancer. The study suggested several reasons why these associations merited further investigation. A later study tested specific relationships between 12 antidepressant drugs and testicular cancer and subtypes thereof; whereas significant relationships were again found, these disappeared after adjusting for confounding variables. These 2 studies are educative because they illustrate how false-positive results can easily arise in exploratory research and how confounding may be responsible for statistically significant relationships in study designs that are not randomized controlled trials. © Copyright 2014 Physicians Postgraduate Press, Inc.

Psychopathology Differences between Batterers and Nonbatterers: Psychosocial Modifiers.

ERIC Educational Resources Information Center

Hamberger, L. Kevin; Hastings, James E.

Research attention on men who batter their female partners has focused on psychological and personality characteristics of the men. However, occupational status, educational attainment, and abuse history may have been confounded with the personality variables studied. This study made within-group and between-group comparisons of batterers and…

Partial Identification of Treatment Effects: Applications to Generalizability

ERIC Educational Resources Information Center

Chan, Wendy

2016-01-01

Results from large-scale evaluation studies form the foundation of evidence-based policy. The randomized experiment is often considered the gold standard among study designs because the causal impact of a treatment or intervention can be assessed without threats of confounding from external variables. Policy-makers have become increasingly…

It Ain't over 'til It's Over: On Foreign Language Anxiety, First Language Deficits, and the Confounding of Variables.

ERIC Educational Resources Information Center

Horwitz, Elaine K.

2000-01-01

Replies on behalf of the authors of a previous article to a critique of their study on foreign language anxiety. Argues that factors other than cognitive-linguistic deficits contribute to problems in foreign language achievement. (Author/VWL)

Multimedia Learning: Are We Still Asking the Wrong Questions?

ERIC Educational Resources Information Center

Rey, Gunter Daniel

2010-01-01

The article discusses problems that arise from comparing different kinds of presentation modes such as texts, pictures or animations with regard to learning outcome. These comparisons are confounded with or depend on other variables like quality of the instructional design, learning content, familiarity with the presentation mode as well as…

The relationship between type D personality and chronic heart failure is not confounded by disease severity as assessed by BNP.

PubMed

Pelle, Aline J; van den Broek, Krista C; Szabó, Balázs; Kupper, Nina

2010-11-05

Psychological factors, like Type D personality (i.e., the tendency to experience negative emotions and to inhibit emotional distress) have been linked to impaired health outcomes. Criticism on the role of psychological factors in cardiac disease has postulated that such constructs may be confounded by disease severity. Hence, we examined whether Type D personality is associated with brain natriuretic peptide (BNP), a sensitive marker of disease severity in chronic heart failure (CHF), in 202 consecutive CHF outpatients. No differences in logBNP levels were found between Type D and non-Type D patients (t(200) = -1.03, p = .30). After adjusting for demographic and clinical confounders, Type D personality remained unassociated with logBNP levels (β=.04, p = .55), whereas older age (β = .27, p<.001), being prescribed beta-blockers (β = .15, p = .02), lower left ventricular ejection fraction (β = -.38, p<.0001), and kidney dysfunction (β = .17, p = .01) were associated with higher logBNP. To conclude, Type D personality was not associated with BNP in CHF outpatients, whereas clinical variables were associated with BNP. These findings oppose the suggestion that Type D personality is confounded by indicators of disease severity. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

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.

Cross-border policy effects on alcohol outcomes: drinking without thinking on the u.s.-Mexico border?

PubMed

Mills, Britain A; Caetano, Raul; Vaeth, Patrice

2014-11-01

Rates of alcohol-related outcomes are sensitive to policy differences in politically distinct, adjacent territories. Factors that shape these cross-border effects, particularly when the policy differences are longstanding, remain poorly understood. We compared the ability of 2 classes of variables with theoretical relevance to the U.S.-Mexico border context-bar attendance and alcohol-related social-cognitive variables-to explain elevated drinking on the U.S. side of the border relative to other areas of the United States. Data were collected from multistage cluster samples of adult Mexican Americans on and off the U.S.-Mexico border (current drinker N = 1,351). Structural equation models were used to test drinking context (frequency of bar attendance) and 6 different social-cognitive variables (including alcohol-related attitudes, norms, motives, and beliefs) as mediators of border effects on a composite drinking index. The border effect on drinking varied by age (with younger adults showing a stronger effect), consistent with previous findings and known risk factors in the region. Contrary to theoretical expectations, 6 different social-cognitive variables-despite relating strongly with drinking-were comparable in border and nonborder areas (within and across age) and played no role in elevated drinking on the border. Conversely, elevated drinking among border youth was mediated by bar attendance. This mediated moderation effect held after adjusting for potential sociodemographic and neighborhood-level confounders. Increased drinking among U.S.-Mexico border youth is explained by patterns of bar attendance, but not by more permissive alcohol-related social-cognitive variables in border areas: Border youth attend bars and drink more than their nonborder counterparts, despite having comparable alcohol-related beliefs, attitudes, norms, and motives for use. Alcohol's heightened availability and visibility on both sides of the border may create opportunities for border youth to drink that otherwise would not be considered. Copyright © 2014 by the Research Society on Alcoholism.

What is the association between wealth and mental health?

PubMed

Carter, K N; Blakely, T; Collings, S; Imlach Gunasekara, F; Richardson, K

2009-03-01

Socioeconomic inequalities in mental health have been shown in a number of populations. This study aims to investigate the association between asset wealth and psychological distress in New Zealand and whether it is independent of other socioeconomic measures and baseline health status. Data for this study were from the first three waves of the Survey of Families, Income and Employment (SoFIE) conducted in New Zealand (2002-2004/05) (n = 15 340). The Kessler-10 was used as a measure of psychological distress. The association of quintiles of wealth with psychological distress was investigated using logistic regression, controlling for confounders, socioeconomic variables and prior health status. The odds ratio (OR) of reporting high psychological distress were greater in the lowest wealth quintile compared with the highest (OR 3.06, 95% CI 2.68 to 3.50). Adjusting for age and sex did not alter the relationship; however, adjusting for income and area deprivation attenuated the OR to 1.73 (95% CI 1.48 to 2.04). Further controlling for baseline health status reduced the OR to 1.45 (95% CI 1.23 to 1.71), although the confidence interval still excluded the null. Inequalities in wealth are strongly associated with psychological distress, over and above other confounding demographic variables and baseline health status. Much, but not all, of that association is confounded by adult socioeconomic position. This suggests that policy measures to improve asset wealth, through savings and home ownership, may have positive health implications and help to reduce health inequalities.

Multisample adjusted U-statistics that account for confounding covariates.

PubMed

Satten, Glen A; Kong, Maiying; Datta, Somnath

2018-06-19

Multisample U-statistics encompass a wide class of test statistics that allow the comparison of 2 or more distributions. U-statistics are especially powerful because they can be applied to both numeric and nonnumeric data, eg, ordinal and categorical data where a pairwise similarity or distance-like measure between categories is available. However, when comparing the distribution of a variable across 2 or more groups, observed differences may be due to confounding covariates. For example, in a case-control study, the distribution of exposure in cases may differ from that in controls entirely because of variables that are related to both exposure and case status and are distributed differently among case and control participants. We propose to use individually reweighted data (ie, using the stratification score for retrospective data or the propensity score for prospective data) to construct adjusted U-statistics that can test the equality of distributions across 2 (or more) groups in the presence of confounding covariates. Asymptotic normality of our adjusted U-statistics is established and a closed form expression of their asymptotic variance is presented. The utility of our approach is demonstrated through simulation studies, as well as in an analysis of data from a case-control study conducted among African-Americans, comparing whether the similarity in haplotypes (ie, sets of adjacent genetic loci inherited from the same parent) occurring in a case and a control participant differs from the similarity in haplotypes occurring in 2 control participants. Copyright © 2018 John Wiley & Sons, Ltd.

What is the relationship between renal function and visit-to-visit blood pressure variability in primary care? Retrospective cohort study from routinely collected healthcare data.

PubMed

Lasserson, Daniel S; Scherpbier de Haan, Nynke; de Grauw, Wim; van der Wel, Mark; Wetzels, Jack F; O'Callaghan, Christopher A

2016-06-10

To determine the relationship between renal function and visit-to-visit blood pressure (BP) variability in a cohort of primary care patients. Retrospective cohort study from routinely collected healthcare data. Primary care in Nijmegen, the Netherlands, from 2007 to 2012. 19 175 patients who had a measure of renal function, and 7 separate visits with BP readings in the primary care record. Visit-to-visit variability in systolic BP, calculated from the first 7 office measurements, including SD, successive variation, absolute real variation and metrics of variability shown to be independent of mean. Multiple linear regression was used to analyse the influence of estimated glomerular filtration rate (eGFR) on BP variability measures with adjustment for age, sex, diabetes, mean BP, proteinuria, cardiovascular disease, time interval between measures and antihypertensive use. In the patient cohort, 57% were women, mean (SD) age was 65.5 (12.3) years, mean (SD) eGFR was 75.6 (18.0) mL/min/1.73m(2) and SD systolic BP 148.3 (21.4) mm Hg. All BP variability measures were negatively correlated with eGFR and positively correlated with age. However, multiple linear regressions demonstrated consistent, small magnitude negative relationships between eGFR and all measures of BP variability adjusting for confounding variables. Worsening renal function is associated with small increases in measures of visit-to-visit BP variability after adjustment for confounding factors. This is seen across the spectrum of renal function in the population, and provides a mechanism whereby chronic kidney disease may raise the risk of cardiovascular events. 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/

Language knowledge and event knowledge in language use

PubMed Central

Willits, Jon A.; Amato, Michael S.; MacDonald, Maryellen C.

2018-01-01

This paper examines how semantic knowledge is used in language comprehension and in making judgments about events in the world. We contrast knowledge gleaned from prior language experience (“language knowledge”) and knowledge coming from prior experience with the world (“world knowledge”). In two corpus analyses, we show that previous research linking verb aspect and event representations have confounded language and world knowledge. Then, using carefully chosen stimuli that remove this confound, we performed four experiments that manipulated the degree to which language knowledge or world knowledge should be salient and relevant to performing a task, finding in each case that participants use the type of knowledge most appropriate to the task. These results provide evidence for a highly context-sensitive and interactionist perspective on how semantic knowledge is represented and used during language processing. PMID:25791750

Language knowledge and event knowledge in language use.

PubMed

Willits, Jon A; Amato, Michael S; MacDonald, Maryellen C

2015-05-01

This paper examines how semantic knowledge is used in language comprehension and in making judgments about events in the world. We contrast knowledge gleaned from prior language experience ("language knowledge") and knowledge coming from prior experience with the world ("world knowledge"). In two corpus analyses, we show that previous research linking verb aspect and event representations have confounded language and world knowledge. Then, using carefully chosen stimuli that remove this confound, we performed four experiments that manipulated the degree to which language knowledge or world knowledge should be salient and relevant to performing a task, finding in each case that participants use the type of knowledge most appropriate to the task. These results provide evidence for a highly context-sensitive and interactionist perspective on how semantic knowledge is represented and used during language processing. Copyright © 2015. Published by Elsevier Inc.

Clinical studies in restorative dentistry: New directions and new demands.

PubMed

Opdam, N J M; Collares, K; Hickel, R; Bayne, S C; Loomans, B A; Cenci, M S; Lynch, C D; Correa, M B; Demarco, F; Schwendicke, F; Wilson, N H F

2018-01-01

Clinical research of restorative materials is confounded by problems of study designs, length of trials, type of information collected, and costs for trials, despite increasing numbers and considerable development of trials during the past 50 years. This opinion paper aims to discuss advantages and disadvantages of different study designs and outcomes for evaluating survival of dental restorations and to make recommendations for future study designs. Advantages and disadvantages of randomized trials, prospective and retrospective longitudinal studies, practice-based, pragmatic and cohort studies are addressed and discussed. The recommendations of the paper are that clinical trials should have rational control groups, include confounders such as patient risk factors in the data and analysis and should use outcome parameters relevant for profession and patients. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Roll-Tilt Perception Using a Somatosensory Bar Task

NASA Technical Reports Server (NTRS)

Black, F. O.; Wade, S. W.; Arshi, A.

1999-01-01

Visual estimates of roll-tilt perception during static roll-tilt are confounded by an offset due to the ocular counterroll that simultaneously occurs. An alternative, non-visual ('somatosensory') measure of roll-tilt perception was developed which is not contaminated by this offset. The aims of this study were to determine: 1) inter-subject variability of somatosensory settings across test session in normal subjects and patients with unilateral or bilateral vestibular loss and 2) intra-subject variability of settings across test session in normal subjects.

Green Space and Depression during Pregnancy: Results from the Growing Up in New Zealand Study

PubMed Central

Nichani, Vikram; Bird, Amy; Grant, Cameron

2017-01-01

Background: Antenatal depression is an important contributor to poor maternal health experienced by some women. This study aimed to determine whether exposure to green space during pregnancy is associated with less depression, and whether this association is moderated by relevant factors, such as age, education, self-identified ethnicity, physical activity, residential rurality, and socioeconomic status. Methods: Health data were sourced from the cohort study “Growing Up in New Zealand” comprised of 6772 participants. Green space was estimated based on the proportion of green space within the Census Area Unit. Adjusted logistic mixed effect models were used to investigate the association between green space and antenatal depression after controlling for confounding variables. Results: Maternal exposure to green space were not associated with lower odds of antenatal depression. Indications of effect modifications due to relevant factors were not observed. Conclusions: This study did not determine an association between access to green space (measured based on the distance to the nearest green space) and antenatal depression. Therefore, a link between green space and antenatal depression was not established. For that reason, ensuring residential areas contain adequate green space may or may not be helpful in preventing antenatal depression and adverse health outcomes associated with this depression. More studies focusing on pregnant women in a range of social contexts, and considering both exposure and access to green space, are warranted to determine the relationships between green space and antenatal depression. PMID:28927014

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

Assessing the Independent Contribution of Maternal Educational Expectations to Children’s Educational Attainment in Early Adulthood: A Propensity Score Matching Analysis

PubMed Central

Pingault, Jean Baptiste; Côté, Sylvana M.; Petitclerc, Amélie; Vitaro, Frank; Tremblay, Richard E.

2015-01-01

Background 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). Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:25803867

Valence, arousal, familiarity, concreteness, and imageability ratings for 292 two-character Chinese nouns in Cantonese speakers in Hong Kong.

PubMed

Yee, Lydia T S

2017-01-01

Words are frequently used as stimuli in cognitive psychology experiments, for example, in recognition memory studies. In these experiments, it is often desirable to control for the words' psycholinguistic properties because differences in such properties across experimental conditions might introduce undesirable confounds. In order to avoid confounds, studies typically check to see if various affective and lexico-semantic properties are matched across experimental conditions, and so databases that contain values for these properties are needed. While word ratings for these variables exist in English and other European languages, ratings for Chinese words are not comprehensive. In particular, while ratings for single characters exist, ratings for two-character words-which often have different meanings than their constituent characters, are scarce. In this study, ratings for 292 two-character Chinese nouns were obtained from Cantonese speakers in Hong Kong. Affective variables, including valence and arousal, and lexico-semantic variables, including familiarity, concreteness, and imageability, were rated in the study. The words were selected from a film subtitle database containing word frequency information that could be extracted and listed alongside the resulting ratings. Overall, the subjective ratings showed good reliability across all rated dimensions, as well as good reliability within and between the different groups of participants who each rated a subset of the words. Moreover, several well-established relationships between the variables found consistently in other languages were also observed in this study, demonstrating that the ratings are valid. The resulting word database can be used in studies where control for the above psycholinguistic variables is critical to the research design.

Meteorological influences on the interannual variability of meningitis incidence in northwest Nigeria.

NASA Astrophysics Data System (ADS)

Abdussalam, Auwal; Monaghan, Andrew; Dukic, Vanja; Hayden, Mary; Hopson, Thomas; Leckebusch, Gregor

2013-04-01

Northwest Nigeria is a region with high risk of bacterial meningitis. Since the first documented epidemic of meningitis in Nigeria in 1905, the disease has been endemic in the northern part of the country, with epidemics occurring regularly. In this study we examine the influence of climate on the interannual variability of meningitis incidence and epidemics. Monthly aggregate counts of clinically confirmed hospital-reported cases of meningitis were collected in northwest Nigeria for the 22-year period spanning 1990-2011. Several generalized linear statistical models were fit to the monthly meningitis counts, including generalized additive models. Explanatory variables included monthly records of temperatures, humidity, rainfall, wind speed, sunshine and dustiness from weather stations nearest to the hospitals, and a time series of polysaccharide vaccination efficacy. The effects of other confounding factors -- i.e., mainly non-climatic factors for which records were not available -- were estimated as a smooth, monthly-varying function of time in the generalized additive models. Results reveal that the most important explanatory climatic variables are mean maximum monthly temperature, relative humidity and dustiness. Accounting for confounding factors (e.g., social processes) in the generalized additive models explains more of the year-to-year variation of meningococcal disease compared to those generalized linear models that do not account for such factors. Promising results from several models that included only explanatory variables that preceded the meningitis case data by 1-month suggest there may be potential for prediction of meningitis in northwest Nigeria to aid decision makers on this time scale.

Pain severity and mobility one year after spinal cord injury: a multicenter, cross-sectional study.

PubMed

Marcondes, Bianca F; Sreepathi, Shruti; Markowski, Justin; Nguyen, Dung; Stock, Shannon R; Carvalho, Sandra; Tate, Denise; Zafonte, Ross; Morse, Leslie R; Fregni, Felipe

2016-10-01

Following a spinal cord injury, patients are often burdened by chronic pain. Preliminary research points to activation of the motor cortex through increased mobility as a potential means of alleviating postinjury chronic pain. The aim of this study was to assess the relationship between pain severity and mobility among patients who have sustained a traumatic spinal cord injury while controlling for clinically-relevant covariates. A multi-center, cross-sectional study. The SCIMS is composed of 14 centers, all located in the United States and funded by the National Institute on Disability and Rehabilitation Research (NIDRR). The study cohort included 1980 patients who completed the one-year SCIMS follow-up assessment between October 2000- December 2013. A multi-center, cross-sectional study was performed to assess the impact of mobility on self-reported pain using information from 1980 subjects who sustained a traumatic spinal cord injury and completed a year-one follow-up interview between October 2000 and December 2013. Patient information was acquired using the Spinal Cord Injury National Database, compiled by the affiliated Spinal Cord Injury Model Systems. Analyses included a multivariable linear regression of patients' self-reported pain scores on mobility, quantified using the CHART-SF mobility total score, and other clinically relevant covariates. After controlling for potential confounders, a significant quadratic relationship between mobility and patients' self-reported pain was observed (P=0.016). Furthermore, female gender, "unemployed" occupational status, paraplegia, and the presence of depressive symptoms were associated with significantly higher pain scores (P<0.02 for all variables). Statistically significant quadratic associations between pain scores and age at injury, life satisfaction total score, and the CHART-SF occupational total subscale were also observed (P≤0.03 for all variables). Among patients with moderate to high levels of mobility, pain scores decreased with increasing mobility. Enhancing a patient's physical activity by increasing his or her mobility may reduce neuropathic pain if begun shortly after a spinal cord injury.

Methodology for the in vitro evaluation of the delivery efficiency from valved holding chambers with facemasks.

PubMed

Xu, Zhen; Hsu, Wenchi; von Hollen, Dirk; Viswanath, Ashwin; Nikander, Kurt; Dalby, Richard

2014-08-01

In vitro performance studies of valved holding chamber (VHC)-facemask systems are a cost-effective means of circumventing potentially confounding clinical variables. This article reports results of an in vitro investigation into VHC-facemask performance, using three age-specific soft anatomical model (SAM) faces, under clinically relevant conditions. A potentially standardized method was developed to assess VHC-facemask seal leakage, and evaluate the in vitro delivery efficiency of conventional and antistatic VHC-facemask systems. A custom-built test rig and VHC cradles were used to position the VHC-facemask systems against the SAM faces, with a constant, reproducible force. A standardized simulated pediatric breathing pattern (tidal volume = 155 mL; inhalation:exhalation ratio = 40:60; 25 breaths/min) was utilized. Percent facemask seal leakage, percent delivered dose, and the effect of different numbers of simulated breaths (2 to 8) were investigated. Of the VHC-facemask systems tested, the OptiChamber Diamond VHC with LiteTouch facemask (Diamond) system had the lowest percent seal leakage with each SAM face. Percent seal leakage from the other VHC-facemask systems was similar with SAM0 and SAM2 faces; the AeroChamber Plus Z-Stat VHC with ComfortSeal facemask (AC Z-Stat) system had a substantially greater percent seal leakage with the SAM1 face. Regardless of the number of simulated breaths, the Diamond system delivered the greatest mean percent delivered dose, with the lowest coefficient of variation, with each SAM face. Percent delivered dose did not correlate well with seal leakage, particularly for VHC-facemask systems with high seal leakage. The electrostatic properties of the VHCs appeared to influence drug delivery. This study describes a potentially standardized method for the evaluation of VHC-facemask systems. Use of this method enabled a comprehensive investigation into the influence of clinically relevant variables, including age-specific facial anatomy, number of simulated breaths, and seal leakage, on the delivery efficiency of several commercially available VHC-facemask systems.

Using ecological propensity score to adjust for missing confounders in small area studies.

PubMed

Wang, Yingbo; Pirani, Monica; Hansell, Anna L; Richardson, Sylvia; Blangiardo, Marta

2017-11-09

Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London. © The Author 2017. Published by Oxford University Press.

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.

The role of noise sensitivity in the noise-response relation: A comparison of three international airport studies

NASA Astrophysics Data System (ADS)

van Kamp, Irene; Job, R. F. Soames; Hatfield, Julie; Haines, Mary; Stellato, Rebecca K.; Stansfeld, Stephen A.

2004-12-01

In order to examine the role of noise sensitivity in response to environmental noise, this paper presents detailed comparisons of socio-acoustic studies conducted around international airports in Amsterdam, Sydney, and London. Earlier findings that noise sensitivity moderates the effect of noise on annoyance were examined to see if they could be replicated in each of the datasets, independent of the technique of measuring noise sensitivity. The relation between exposure to aircraft noise and noise annoyance was studied separately for groups of individuals with low, medium, and high noise sensitivity, with statistical adjustment for relevant confounders. Results support the previous findings that noise sensitivity is an independent predictor of annoyance and adds to the prediction of noise annoyance afforded by noise exposure level by up to 26% of explained variance. There is no evidence of a moderating effect, whereby the covariation between noise exposure level and annoyance is weak for people who score at the extreme high or low end of the sensitivity scale, and strong for people who score in the middle of the sensitivity scale. Generally, noise sensitivity appears to increase annoyance independently of the level of noise exposure after adjustment for relevant confounders. These findings were consistent across the three datasets. .

Small and Large Number Processing in Infants and Toddlers with Williams Syndrome

ERIC Educational Resources Information Center

Van Herwegen, Jo; Ansari, Daniel; Xu, Fei; Karmiloff-Smith, Annette

2008-01-01

Previous studies have suggested that typically developing 6-month-old infants are able to discriminate between small and large numerosities. However, discrimination between small numerosities in young infants is only possible when variables continuous with number (e.g. area or circumference) are confounded. In contrast, large number discrimination…

Using Learning Analytics to Characterize Student Experimentation Strategies in Engineering Design

ERIC Educational Resources Information Center

Vieira, Camilo; Goldstein, Molly Hathaway; Purzer, Senay; Magana, Alejandra J.

2016-01-01

Engineering design is a complex process both for students to participate in and for instructors to assess. Informed designers use the key strategy of conducting experiments as they test ideas to inform next steps. Conversely, beginning designers experiment less, often with confounding variables. These behaviours are not easy to assess in…

Growth and physiology of aspen supplied with different fertilizer addition rates

Treesearch

Mark D. Coleman; Richard E. Dickson; J.G. Isebrands

1998-01-01

Variable internal plant nutrient content may confound plant response to environmental stress. Plant nutrient content may be controlled with relative addition rate techniques in solution culture. However, because raising large numbers of plants in flowing solution culture is difficult. we investieated the feasibility of raisine plants in soil mix using relative...

Neighborhood Frequency Effect in Chinese Word Recognition: Evidence from Naming and Lexical Decision

ERIC Educational Resources Information Center

Li, Meng-Feng; Gao, Xin-Yu; Chou, Tai-Li; Wu, Jei-Tun

2017-01-01

Neighborhood frequency is a crucial variable to know the nature of word recognition. Different from alphabetic scripts, neighborhood frequency in Chinese is usually confounded by component character frequency and neighborhood size. Three experiments were designed to explore the role of the neighborhood frequency effect in Chinese and the stimuli…

Impact of Trauma Work on Social Work Clinicians: Empirical Findings.

ERIC Educational Resources Information Center

Cunningham, Maddy

2003-01-01

Describes a study of social work clinicians working with two types of trauma: sexual abuse and cancer. The effect of clinician's cognitive schemas and the confounding variables of personal history of abuse and years' experience are described. Clinicians who worked primarily with clients who were sexually abused reported more disruptions in…

Maternal Age at Childbirth and Offspring Disruptive Behaviors: Testing the Causal Hypothesis

ERIC Educational Resources Information Center

D'Onofrio, Brian M.; Goodnight, Jackson A.; Van Hulle, Carol A.; Rodgers, Joseph Lee; Rathouz, Paul J.; Waldman, Irwin D.; Lahey, Benjamin B.

2009-01-01

Background: Recent studies suggest that the association between maternal age at childbearing (MAC) and children's disruptive behaviors is the result of family factors that are confounded with both variables, rather than a casual effect of environmental factors specifically related to MAC. These studies, however, relied on restricted samples and…

Long-Term Positive Associations between Music Lessons and IQ

ERIC Educational Resources Information Center

Schellenberg, E. Glenn

2006-01-01

In Study 1 (N = 147), duration of music lessons was correlated positively with IQ and with academic ability among 6-to 11-year-olds, even when potential confounding variables (i.e., family income, parents' education, involvement in nonmusical activities) were held constant. In Study 2 (N = 150), similar but weaker associations between playing…

“Skill of Generalized Additive Model to Detect PM2.5 Health Signal in the Presence of Confounding Variables”

EPA Science Inventory

Summary. Measures of health outcomes are collinear with meteorology and air quality, making analysis of connections between human health and air quality difficult. The purpose of this analysis was to determine time scales and periods shared by the variables of interest (and...

Influences of Phonological Context on Tense Marking in Spanish-English Dual Language Learners

ERIC Educational Resources Information Center

Combiths, Philip N.; Barlow, Jessica A.; Potapova, Irina; Pruitt-Lord, Sonja

2017-01-01

Purpose: The emergence of tense-morpheme marking during language acquisition is highly variable, which confounds the use of tense marking as a diagnostic indicator of language impairment in linguistically diverse populations. In this study, we seek to better understand tense-marking patterns in young bilingual children by comparing phonological…

International Business, Gender, and Training: Preparing for the Global Economy.

ERIC Educational Resources Information Center

Hugenberg, Lawrence W.; And Others

This paper deals with how to train employees in transnational companies to be more "global" in their understanding and awareness of different cultures. The paper defines as "target culture" where the employee or his family will be working and considers as a confounding variable in the international marketplace the role to be…

The Sensitivity of the Right Hemisphere to Contextual Information in Sentences

ERIC Educational Resources Information Center

Gouldthorp, Bethanie; Coney, Jeffrey

2009-01-01

One explanation for the inconsistencies in research examining the sentence comprehension abilities of the right hemisphere (RH) is the presence of confounding variables that have generally served to disadvantage the processing capacities of the RH. As such, the present study aimed to investigate hemispheric differences in the use of message-level…

Learning at the Speed of Light: Deep Learning and Accelerated Online Graduate Courses

ERIC Educational Resources Information Center

Trekles, Anastasia M.

2013-01-01

An increasing number of university programs, particularly at the graduate level, are moving to an accelerated, time-compressed model for online degree offerings. However, the literature revealed that research in distance education effectiveness is still confounded by many variables, including course design and student approach to learning.…

Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation.

PubMed

Brasic, J R; Barnett, J Y; Kaplan, D; Sheitman, B B; Aisemberg, P; Lafargue, R T; Kowalik, S; Clark, A; Tsaltas, M O; Young, J G

1994-07-01

In an open, nonblind clinical trial, clomipramine reduced adventitious movements and compulsions in five previously medicated prepubertal boys with autistic disorder and severe mental retardation. Poorly adapted rating scales, interrater variability, subject heterogeneity, different treatment histories, and environmental stresses confounded the assessment of treatment effects.

The diurnal course of salivary alpha-amylase in nurses: an investigation of potential confounders and associations with stress.

PubMed

Wingenfeld, Katja; Schulz, Michael; Damkroeger, Annika; Philippsen, Christine; Rose, Matthias; Driessen, Martin

2010-09-01

In psychoneuroendocrinology research, salivary measures have become increasingly important. While several studies focus on determinants of salivary cortisol such as age, gender, and gynaecological variables, less research has focused on confounding variables of salivary alpha-amylase (sAA). In a large sample of nurses (N=215) we analyzed the impact of age, gender, intake of oral contraceptives, smoking, coffee consumption as well as psychological parameters, such as work stress and burnout, on basal diurnal sAA release. Saliva was collected at 07:00 h, 11:30 h, 17:30 h, and 20:00 h on a working day during early shift. Only gender could be identified to have an impact on sAA, with females having a more pronounced sAA increase over the course of the day. Whereas depression, anxiety, work stress and burnout were not associated with sAA, a small negative correlation between social difficulties, measured with the Chronic Stress Screening Scale, and sAA could be identified. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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.

Peritraumatic tonic immobility is associated with posttraumatic stress symptoms in undergraduate Brazilian students.

PubMed

Portugal, Liana Catarina L; Pereira, Mirtes Garcia; Alves, Rita de Cássia S; Tavares, Gisella; Lobo, Isabela; Rocha-Rego, Vanessa; Marques-Portella, Carla; Mendlowicz, Mauro V; Coutinho, Evandro S; Fiszman, Adriana; Volchan, Eliane; Figueira, Ivan; Oliveira, Letícia de

2012-03-01

Tonic immobility is a defensive reaction occurring under extreme life threats. Patients with posttraumatic stress disorder (PTSD) reporting peritraumatic tonic immobility show the most severe symptoms and a poorer response to treatment. This study investigated the predictive value of tonic immobility for posttraumatic stress symptoms in a non-clinical sample. One hundred and ninety-eight college students exposed to various life threatening events were selected to participate. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and tonic immobility questions were used. Linear regression models were fitted to investigate the association between peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation, peritraumatic panic reactions, negative affect, gender, type of trauma, and time since trauma were considered as confounding variables. We found significant association between peritraumatic tonic immobility and PTSD symptoms in a non-clinical sample exposed to various traumas, even after regression controlled for confounding variables (β = 1.99, p = 0.017). This automatic reaction under extreme life threatening stress, although adaptive for defense, may have pathological consequences as implied by its association with PTSD symptoms.

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.

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.

Variations in thematic mapper spectra of soil related to tillage and crop residue management - Initial evaluation

NASA Technical Reports Server (NTRS)

Seeley, M. W.; Ruschy, D. L.; Linden, D. R.

1983-01-01

A cooperative research project was initiated in 1982 to study differences in thematic mapper spectral characteristics caused by variable tillage and crop residue practices. Initial evaluations of radiometric data suggest that spectral separability of variably tilled soils can be confounded by moisture and weathering effects. Separability of bare tilled soils from those with significant amounts of corn residue is enhanced by wet conditions, but still possible under dry conditions when recent tillage operations have occurred. In addition, thematic mapper data may provide an alternative method to study the radiant energy balance at the soil surface in conjunction with variable tillage systems.

Reading Behind the Lines: The Factors Affecting the Text Reception Threshold in Hearing Aid Users.

PubMed

Zekveld, Adriana A; Pronk, Marieke; Danielsson, Henrik; Rönnberg, Jerker

2018-03-15

The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007) has been designed to assess modality-general factors relevant for speech perception in noise. In the last decade, the test has been adopted in audiology labs worldwide. The 1st aim of this study was to examine which factors best predict interindividual differences in the TRT. Second, we aimed to assess the relationships between the TRT and the speech reception thresholds (SRTs) estimated in various conditions. First, we reviewed studies reporting relationships between the TRT and the auditory and/or cognitive factors and formulated specific hypotheses regarding the TRT predictors. These hypotheses were tested using a prediction model applied to a rich data set of 180 hearing aid users. In separate association models, we tested the relationships between the TRT and the various SRTs and subjective hearing difficulties, while taking into account potential confounding variables. The results of the prediction model indicate that the TRT is predicted by the ability to fill in missing words in incomplete sentences, by lexical access speed, and by working memory capacity. Furthermore, in line with previous studies, a moderate association between higher age, poorer pure-tone hearing acuity, and poorer TRTs was observed. Better TRTs were associated with better SRTs for the correct perception of 50% of Hagerman matrix sentences in a 4-talker babble, as well as with better subjective ratings of speech perception. Age and pure-tone hearing thresholds significantly confounded these associations. The associations of the TRT with SRTs estimated in other conditions and with subjective qualities of hearing were not statistically significant when adjusting for age and pure-tone average. We conclude that the abilities tapped into by the TRT test include processes relevant for speeded lexical decision making when completing partly masked sentences and that these processes require working memory capacity. Furthermore, the TRT is associated with the SRT of hearing aid users as estimated in a challenging condition that includes informational masking and with experienced difficulties with speech perception in daily-life conditions. The current results underline the value of using the TRT test in studies involving speech perception and aid in the interpretation of findings acquired using the test.

Aggression, Suicidality, and Intermittent Explosive Disorder: Serotonergic Correlates in Personality Disorder and Healthy Control Subjects

PubMed Central

Coccaro, Emil F; Lee, Royce; Kavoussi, Richard J

2010-01-01

Central serotonergic (5-HT) activity has long been implicated in the regulation of impulsive aggressive behavior. This study was performed to use a highly selective agent for 5-HT (d-Fenfluramine, d-FEN) in a large group of human subjects to further explore this relationship dimensionally and categorically. One hundred and fifty healthy subjects (100 with personality disorder, PD and 50 healthy volunteer controls, HV) underwent d-FEN challenge studies. Residual peak delta prolactin (ΔPRL[d-FEN]-R; ie, after the removal of potentially confounding variables) was used as the primary 5-HT response variable. Composite measures of aggression and impulsivity were used as dimensional measures, and history of suicidal/self-injurious behavior as well as the presence of intermittent explosive disorder (IED) were used as categorical variables. ΔPRL[d-FEN]-R responses correlated inversely with composite aggression, but not composite impulsivity, in all subjects and in males and females examined separately. The correlation with composite aggression was strongest in male PD subjects. ΔPRL[d-FEN]-R values were reduced in PD subjects with a history of suicidal behavior but not, self-injurious behavior. ΔPRL[d-FEN]-R values were also reduced in patients meeting Research Criteria for IED. Physiologic responses to 5-HT stimulation are reduced as a function of aggression (but not generalized impulsivity) in human subjects. The same is true for personality disordered subjects with a history of suicidal, but not self-injurious, behavior and for subjects with a diagnosis of IED by research criteria. These data have particular relevance to the notion of impulsive aggression and the biological validity of IED. PMID:19776731

Periodontitis is associated with diabetic retinopathy in non-obese adults.

PubMed

Song, Su Jeong; Lee, Seong-Su; Han, Kyungdo; Park, Jun-Beom

2017-04-01

Patients with diabetes retinopathy appear to show increased susceptibility to periodontal disease. This study was performed to assess the relationship between periodontitis and the prevalence of diabetic retinopathy in a large probability sample of the Korean population. A subgroup analysis was performed using body mass index <25 kg/m 2 as the criterion to evaluate the effect of obesity on this relationship. This study is based on data from the Korean National Health and Nutrition Examination Survey of the Korean population, conducted between 2008 and 2010. The presence of diabetic retinopathy in relation to demographic variables and anthropometric characteristics of the participants is presented as means with their standard errors. The presence of periodontitis and presence of retinopathy categorized by body mass index (<25 and ≥25 kg/m 2 ) were evaluated. Multiple logistic regression analyses were used to assess the associations between periodontitis and diabetic retinopathy after adjustment with variables, including age, sex, smoking, drinking, exercise, hypertension, metabolic syndrome, HbA1c, and duration of diabetes mellitus. There was a statistically significant increase in the prevalence of periodontitis in individuals who had proliferative diabetic retinopathy. The odds ratios [95% confidence intervals] of prevalence of diabetic retinopathy were 1.193 [0.757-1.881] for the whole population after adjustments with confounding factors. Subgroup analysis after adjustments with confounding factors showed that the odds ratios [95% confidence intervals] of prevalence were 2.206 [1.114-4.366] and 0.588 [0.326-1.061] among participants with body mass index <25 kg/m 2 and body mass index 37 ≥25 kg/m 2 , respectively. The diabetic retinopathy was positively associated with the presence of periodontitis in non-obese diabetic Korean adults after adjustment with confounding variables. Our findings suggest that when a periodontist finds the presence of periodontitis in non-obese diabetic patients, timely evaluation of the patient's ophthalmic evaluation should be 44 recommended.

Assessment of the number of eye symptoms and the impact of some confounding variables for office staff in non-air-conditioned buildings.

PubMed

Doughty, Michael J; Blades, Kenneth A; Ibrahim, Nassim

2002-03-01

The goal of this study was both to assess the frequency of self-reported eye symptoms for employees in a non-air-conditioned office building complex, and to specifically assess whether confounding variables (contact lens wear, medicines use, and provoking stimuli) had a discernible impact on the characteristics of this reporting. A questionnaire was distributed, in the winter months, to office employees in a building complex within a city-located University site, consisting of non-air-conditioned rooms with some mechanical ventilation. The questionnaire asked respondents to identify any eye symptoms experienced (foreign body sensation, soreness, dryness, grittiness, itchiness, stinging, intense burning), the frequency of their occurrence, details of any conditions provoking eye symptoms (such as changes in the microenvironment), their medication use and if they were contact lens wearers. The proportion of respondents for various categories was calculated, along with the total number of symptoms. If 'eye irritation' is considered as reporting any symptoms experienced at any time, then 63% of 292 respondents (median age 42.5 years) reported an average of 1.83 symptoms. However, the identification of contact lens wearers, medication use (especially for seasonal allergies) and provoking stimuli reduced this prevalence to just 29% (with the average number of symptoms being 1.51). If the frequency of experiencing symptoms was also taken into account (never, sometimes, often, and constantly), then only 12.3% of the respondents indicated symptoms often or constantly, i.e. could be considered to have significant symptoms. In all categories, men were more likely to report eye symptoms compared with women. The results confirm that office employees are likely to have some ocular symptoms, but that even a simple consideration of possible confounding variables can greatly change the reported prevalence of eye irritation that might be specifically associated with the workplace environment.

Does the frequency of anxiety and depressive disorders differ between diagnostic subtypes of anorexia nervosa and bulimia?

PubMed

Godart, Nathalie; Berthoz, Sylvie; Rein, Zoé; Perdereau, Fabienne; Lang, François; Venisse, Jean-Luc; Halfon, Olivier; Bizouard, Pierre; Loas, Gwénolé; Corcos, Maurice; Jeammet, Philippe; Flament, Martine; Curt, Florence

2006-12-01

The objective of the present work is to determine whether the prevalence of depressive and anxiety disorders varies in subgroups of eating disorders (ED) according to age, ED duration, mode of care provision, and body mass index (BMI). Using the Mini International Neuropsychiatric Interview (MINI), the frequency of anxiety and depressive disorders was evaluated in 271 ED participants. Their prevalence was compared in subgroups of anorexics (AN-R and AN-BN) and bulimics (BN), both before and after controlling for potential confounding variables. Current or lifetime comorbidity of anxiety and depressive disorders did not differ between AN-R and AN-BN groups. Social phobia, panic disorders, and obsessive-compulsive disorder (OCD) were significantly more frequent in AN-BN and AN-R groups. Panic disorder was more frequent in the BN group. Several confounding factors, in particular those identified in the present study, may explain previous conflicting results on the frequency of anxiety and depressive disorders in ED. Nevertheless, the study confirmed that OCD is more frequent in AN, even after controlling for confounding factors. Copyright 2006 by Wiley Periodicals, Inc.

Progression-free survival as a primary endpoint in clinical trials of metastatic colorectal cancer

PubMed Central

Gill, S.; Berry, S.; Biagi, J.; Butts, C.; Buyse, M.; Chen, E.; Jonker, D.; Mărginean, C.; Samson, B.; Stewart, J.; Thirlwell, M.; Wong, R.; Maroun, J.A.

2011-01-01

In recent years, significant advances have been made in the management of metastatic colorectal cancer. Traditionally, an improvement in overall survival has been considered the “gold standard”—the most convincing measure of efficacy. However, overall survival requires larger patient numbers and longer follow-up and may often be confounded by other factors, including subsequent therapies and crossover. Given the number of active therapies for potential investigation, demand for rapid evaluation and early availability of new therapies is growing. Progression-free survival is regarded as an important measure of treatment benefit and, compared with overall survival, can be evaluated earlier, with fewer patients and no confounding by subsequent lines of therapy. The present paper reviews the advantages, limitations, and relevance of progression-free survival as a primary endpoint in randomized trials of metastatic colorectal cancer. PMID:21969810

Human punishment is not primarily motivated by inequality.

PubMed

Marczyk, Jesse

2017-01-01

Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.

Higher screen time is associated with overweight, poor dietary habits and physical inactivity in Brazilian adolescents, mainly among girls.

PubMed

Christofaro, Diego Giulliano Destro; De Andrade, Selma Maffei; Mesas, Arthur Eumann; Fernandes, Rômulo Araújo; Farias Júnior, José Cazuza

2016-01-01

To analyse the associations between high screen time and overweight, poor dietary habits and physical activity in adolescents according to sex. The study comprised 515 boys and 716 girls aged 14-17 years from Londrina, Brazil. Nutritional status (normal weight or overweight/obese) was assessed by calculating the body mass index. Eating habits and time spent in physical activity were reported using a questionnaire. The measurement of screen time considered the time spent watching television, using a computer and playing video games during a normal week. Associations between high screen time and dependent variables (nutritional status, eating habits and physical activity levels) were assessed by binary logistic regression, adjusted for sociodemographic and lifestyle variables. Most adolescents (93.8% of boys and 87.2% of girls) spent more than 2 hours per day in screen-time activities. After adjustments, an increasing trend in the prevalence of overweight and physical inactivity with increasing time spent on screen activities was observed for both sexes. Screen times of >4 hours/day compared with <2 hours/day were associated with physical inactivity, low consumption of vegetables and high consumption of sweets only in girls and the consumption of soft drinks in both sexes. The frequency of overweight and physical inactivity increased with increasing screen time in a trending manner and independently of the main confounders. The relationship between high screen time and poor eating habits was particularly relevant for adolescent girls.

Supervisor Autonomy and Considerate Leadership Style are Associated with Supervisors' Likelihood to Accommodate Back Injured Workers.

PubMed

McGuire, Connor; Kristman, Vicki L; Shaw, William; Williams-Whitt, Kelly; Reguly, Paula; Soklaridis, Sophie

2015-09-01

To determine the association between supervisors' leadership style and autonomy and supervisors' likelihood of supporting job accommodations for back-injured workers. A cross-sectional study of supervisors from Canadian and US employers was conducted using a web-based, self-report questionnaire that included a case vignette of a back-injured worker. Autonomy and two dimensions of leadership style (considerate and initiating structure) were included as exposures. The outcome, supervisors' likeliness to support job accommodation, was measured with the Job Accommodation Scale (JAS). We conducted univariate analyses of all variables and bivariate analyses of the JAS score with each exposure and potential confounding factor. We used multivariable generalized linear models to control for confounding factors. A total of 796 supervisors participated. Considerate leadership style (β = .012; 95% CI .009-.016) and autonomy (β = .066; 95% CI .025-.11) were positively associated with supervisors' likelihood to accommodate after adjusting for appropriate confounding factors. An initiating structure leadership style was not significantly associated with supervisors' likelihood to accommodate (β = .0018; 95% CI -.0026 to .0061) after adjusting for appropriate confounders. Autonomy and a considerate leadership style were positively associated with supervisors' likelihood to accommodate a back-injured worker. Providing supervisors with more autonomy over decisions of accommodation and developing their considerate leadership style may aid in increasing work accommodation for back-injured workers and preventing prolonged work disability.

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.

Instrumental variable applications using nursing home prescribing preferences in comparative effectiveness research.

PubMed

Huybrechts, Krista F; Gerhard, Tobias; Franklin, Jessica M; Levin, Raisa; Crystal, Stephen; Schneeweiss, Sebastian

2014-08-01

Nursing home residents are of particular interest for comparative effectiveness research given their susceptibility to adverse treatment effects and systematic exclusion from trials. However, the risk of residual confounding because of unmeasured markers of declining health using conventional analytic methods is high. We evaluated the validity of instrumental variable (IV) methods based on nursing home prescribing preference to mitigate such confounding, using psychotropic medications to manage behavioral problems in dementia as a case study. A cohort using linked data from Medicaid, Medicare, Minimum Data Set, and Online Survey, Certification and Reporting for 2001-2004 was established. Dual-eligible patients ≥65 years who initiated psychotropic medication use after admission were selected. Nursing home prescribing preference was characterized using mixed-effects logistic regression models. The plausibility of IV assumptions was explored, and the association between psychotropic medication class and 180-day mortality was estimated. High-prescribing and low-prescribing nursing homes differed by a factor of 2. Each preference-based IV measure described a substantial proportion of variation in psychotropic medication choice (β(IV → treatment): 0.22-0.36). Measured patient characteristics were well balanced across patient groups based on instrument status (52% average reduction in Mahalanobis distance). There was no evidence that instrument status was associated with markers of nursing home quality of care. Findings indicate that IV analyses using nursing home prescribing preference may be a useful approach in comparative effectiveness studies, and should extend naturally to analyses including untreated comparison groups, which are of great scientific interest but subject to even stronger confounding. Copyright © 2014 John Wiley & Sons, Ltd.

Prenatal Maternal Stress Associated with ADHD and Autistic Traits in early Childhood

PubMed Central

Ronald, Angelica; Pennell, Craig E.; Whitehouse, Andrew J. O.

2010-01-01

Research suggests that offspring of mothers who experience high levels of stress during pregnancy are more likely to have problems in neurobehavioral development. There is preliminary evidence that prenatal maternal stress (PNMS) is a risk factor for both autism and attention deficit hyperactivity disorder (ADHD), however most studies do not control for confounding factors and no study has investigated PNMS as a risk factor for behaviors characteristic of these disorders in early childhood. A population cohort of 2900 pregnant women were recruited before their 18th week of pregnancy and investigated prospectively. Maternal experience of stressful life events was assessed during pregnancy. When offspring were age 2 years, mothers completed the child behavior checklist. Multiple regression showed that maternal stressful events during pregnancy significantly predicted ADHD behaviors in offspring, after controlling for autistic traits and other confounding variables, in both males (p = 0.03) and females (p = 0.01). Similarly, stressful events during pregnancy significantly predicted autistic traits in the offspring after controlling for ADHD behaviors and confounding variables, in males only (p = 0.04). In conclusion, this study suggests that PNMS, in the form of typical stressful life events such as divorce or a residential move, show a small but significant association with both autistic traits and ADHD behaviors independently, in offspring at age 2 years, after controlling for multiple antenatal, obstetric, postnatal, and sociodemographic covariates. This finding supports future research using epigenetic, cross-fostering, and gene–environment interaction designs to identify the causal processes underlying this association. PMID:21833278

Administrative Databases in Orthopaedic Research: Pearls and Pitfalls of Big Data.

PubMed

Patel, Alpesh A; Singh, Kern; Nunley, Ryan M; Minhas, Shobhit V

2016-03-01

The drive for evidence-based decision-making has highlighted the shortcomings of traditional orthopaedic literature. Although high-quality, prospective, randomized studies in surgery are the benchmark in orthopaedic literature, they are often limited by size, scope, cost, time, and ethical concerns and may not be generalizable to larger populations. Given these restrictions, there is a growing trend toward the use of large administrative databases to investigate orthopaedic outcomes. These datasets afford the opportunity to identify a large numbers of patients across a broad spectrum of comorbidities, providing information regarding disparities in care and outcomes, preoperative risk stratification parameters for perioperative morbidity and mortality, and national epidemiologic rates and trends. Although there is power in these databases in terms of their impact, potential problems include administrative data that are at risk of clerical inaccuracies, recording bias secondary to financial incentives, temporal changes in billing codes, a lack of numerous clinically relevant variables and orthopaedic-specific outcomes, and the absolute requirement of an experienced epidemiologist and/or statistician when evaluating results and controlling for confounders. Despite these drawbacks, administrative database studies are fundamental and powerful tools in assessing outcomes on a national scale and will likely be of substantial assistance in the future of orthopaedic research.

Nutrient supplementation as adjunct therapy in pulmonary tuberculosis.

PubMed

Chandra, Ranjit Kumar

2004-03-01

The study examined the effect of supplementation with multivitamins and trace elements on microbiological and radiological recovery in patients with pulmonary tuberculosis. Forty-four patients aged 28-50 years were diagnosed with active pulmonary tuberculosis based on X-ray of the chest and smear examination of the sputum for the presence of acid-fast bacilli. They were all treated for six months with a standard anti-tuberculosis regimen that has been found to be effective worldwide for disease control. The subjects were randomized to receive either a multivitamin-trace element supplement or a placebo containing calcium. The two groups were matched on all relevant confounding variables. At two months into the treatment, the group that was supplemented with a multivitamin-trace element preparation showed a significant reduction in the number of individuals with sputum smear positive for acid-fast bacillus: two out of 22 individuals, compared with seven out of 22 among placebo-treated controls (p = 0.028, Fisher's test). It is concluded that patients with tuberculosis should be supplemented with a suitable micronutrient preparation that contains optimum amounts of all vitamins and trace elements that have been documented to enhance the immune response.

The Well-Being of Siblings of Individuals with Autism

PubMed Central

Green, Laura

2013-01-01

Objective. The purpose of this review of the literature was to summarise studies regarding the psychosocial impact of growing up with a sibling with autism and to identify gaps in the related literature. Methods. Electronic databases were reviewed in order to critically appraise the 14 articles relevant to the topic. The search included a combination of the following key words: autism∗, quality of life, well-being, sibling∗, ASD, ASD sibling∗, family, adjust∗, psychological functioning. Results. The majority of studies involved mixed children and adolescent samples, leading to confounding results and an inability to draw accurate conclusions about these distinct life stages. Autism appears to contribute to unique environmental stressors for the typically developing sibling. When experienced in the context of additional demographic risk factors, these stressors can result in difficulties adjusting to the demands of a special-needs child. Despite some vulnerability to behavioural and emotional dysfunction in at-risk children, siblings have the potential to not only adjust but to thrive in the face of disability adversity. Conclusion. Growing up with a sibling with autism appears to manifest in both positive and negative outcomes for siblings, depending upon important demographical, family, and individual variables. PMID:23738144

Pharmacogenetics and pharmacogenomics in psoriasis treatment: current challenges and future prospects.

PubMed

Sutherland, Alison; Power, Rebecca J; Rahman, Proton; O'Rielly, Darren D

2016-08-01

Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events. This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis. Presently, no clinically actionable biomarker exists for any therapeutic agent used to treat psoriasis or psoriatic arthritis. The lack of validated outcome measures and conflicting results of open-label studies conducted may be attributed to a multitude of issues that confound discovery. Consequently, studies have been underpowered to identify genes or genetic variants worth translating to clinical practice. In order to achieve a pharmacogenetic/pharmacogenomic signature, improvements in study design of future investigations are required, including carefully designed prospective studies. It is imperative to combine known clinical, serological, and molecular markers with consistent outcomes and an adequate health economic evaluation before they can be adopted widely in clinical practice.

Temperature variability during delirium in ICU patients: an observational study.

PubMed

van der Kooi, Arendina W; Kappen, Teus H; Raijmakers, Rosa J; Zaal, Irene J; Slooter, Arjen J C

2013-01-01

Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and -nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. We included patients who experienced both delirium and delirium free days during ICU stay, based on the Confusion Assessment method for the ICU conducted by a research- physician or -nurse, in combination with inspection of medical records. We excluded patients with conditions affecting thermal regulation or therapies affecting body temperature. Daily temperature variability was determined by computing the mean absolute second derivative of the temperature signal. Temperature variability (primary outcome) and absolute body temperature (secondary outcome) were compared between delirium- and non-delirium days with a linear mixed model and adjusted for daily mean Richmond Agitation and Sedation Scale scores and daily maximum Sequential Organ Failure Assessment scores. Temperature variability was increased during delirium-days compared to days without delirium (β(unadjuste)d=0.007, 95% confidence interval (CI)=0.004 to 0.011, p<0.001). Adjustment for confounders did not alter this result (β(adjusted)=0.005, 95% CI=0.002 to 0.008, p<0.001). Delirium was not associated with absolute body temperature (β(unadjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.61). This did not change after adjusting for confounders (β(adjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.63). Our study suggests that temperature variability is increased during ICU delirium.

The Relation between Binge Drinking and Academic Performance: Considering the Mediating Effects of Academic Involvement

ERIC Educational Resources Information Center

An, Brian P.; Loes, Chad N.; Trolian, Teniell L.

2017-01-01

Using longitudinal data from multiple institutions, we focused on the relation between binge drinking and academic performance. Binge drinking exerts a negative influence on grade point average, even after accounting for a host of precollege confounding variables. Furthermore, the number of times a student binge drinks in college is less…

Stress-Disorder Symptoms in Vietnam and Korean War Veterans: A Commentary on Thienes-Hontos, Watson, and Kucala.

ERIC Educational Resources Information Center

Caroll, Edward

1983-01-01

Reviews a study which found that symptoms associated with posttraumatic stress disorder (PTSD) are neither unique to or common among Vietnam veteran psychiatric patients or their Korean war counterparts. Questions choice of study sample, confounding variables, and source of data. A rebuttal by the original author is included. (WAS)

Root disease and other unforeseen variables that confound restoration efforts

Treesearch

William J. Otrosina; Shi-Jean S. Sung; Stanley J. Zarnoch; Brian T. Sullivan; Charles H. Walkinshaw

2002-01-01

Unanticipated disease problems thwarting restoration efforts can emerge in forest ecosystems. An example is the longleaf pine (Pinus palustris Mill.) ecosystem. This species once occupied nearly 30 million ha but now its range is reduced to approximately 1.5 million ha. Restoring longleaf pine to many sites in its former range is an important goal...

Gender Bias in the Diagnosis of a Geriatric Standardized Patient: A Potential Confounding Variable

ERIC Educational Resources Information Center

Lewis, Roya; Lamdan, Ruth M.; Wald, David; Curtis, Michael

2006-01-01

Background: Gender bias has been reported in the diagnosis and treatment of patients with a variety of illnesses. In the context of our 10-station fourth year Objective Structured Clinical Evaluation, we queried whether this could influence diagnosis in a geriatric case. Case writers hypothesized that, due to this bias, the female standardized…

Typing Speed as a Confounding Variable and the Measurement of Quality in Divergent Thinking

ERIC Educational Resources Information Center

Forthmann, Boris; Holling, Heinz; Çelik, Pinar; Storme, Martin; Lubart, Todd

2017-01-01

The need to control for writing or typing speed when assessing divergent-thinking performance has been recognized since the early '90s. An even longer tradition in divergent-thinking research has the issue of scoring the responses for quality. This research addressed both issues within structural equation modeling. Three dimensions of…

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.

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.

Work-Home Interference, Perceived Total Workload, and the Risk of Future Sickness Absence Due to Stress-Related Mental Diagnoses Among Women and Men: a Prospective Twin Study.

PubMed

Svedberg, Pia; Mather, Lisa; Bergström, Gunnar; Lindfors, Petra; Blom, Victoria

2018-02-01

Work-home interference has been proposed as an important explanation for sickness absence (SA). Previous studies show mixed results, have not accounted for familial factors (genetics and shared everyday environment), or investigated diagnosis specific SA. The aim was to study whether work-home interference and perceived total workload predict SA due to stress-related mental diagnoses, or SA due to other mental diagnoses, among women and men, when adjusting for various confounders and familial factors. This study included 11,916 twins, 19-47 years (49% women). Data on work-to-home and home-to-work conflicts, perceived total workload, and relevant confounders were derived from a 2005 survey, and national register data on SA spells until 2013 were obtained. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Discordant twin pair design was applied to adjust for familial factors. Each one unit increase in work-to-home and home-to-work conflicts, and perceived total workload was associated with higher odds for SA due to stress-related mental diagnoses and to SA due to other mental diagnoses among women, when adjusting for sociodemographic factors (ORs 1.15-1.31). Including health or familial factors, no associations remained. For men, each one unit increase in work-to-home conflicts was associated with higher odds for SA due to stress-related diagnoses (ORs 1.23-1.35), independently of confounders. Work-to-home conflict was independently associated with future SA due to stress-related diagnoses among men only. Health- and work-related factors seem to be important confounders when researching work-home interference, perceived total workload, and SA. Not including such confounders involves risking drawing incorrect conclusions. Further studies are needed to confirm sex differences and whether genetic factors are important for the associations studied.

Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

PubMed

Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

2018-01-01

With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified the suggested association. Increased homocysteine is thought to be associated with vitamin B12 deficiency - evaluation for potential clinical relevance is suggested. While considerations for clinical metabolic profiling are recommended, including adjustment approaches for clinical confounders, AutoML presents an exciting tool to enhance clinical metabolic profiling and advance translational research endeavors.

Squeezing observational data for better causal inference: Methods and examples for prevention research.

PubMed

Garcia-Huidobro, Diego; Michael Oakes, J

2017-04-01

Randomised controlled trials (RCTs) are typically viewed as the gold standard for causal inference. This is because effects of interest can be identified with the fewest assumptions, especially imbalance in background characteristics. Yet because conducting RCTs are expensive, time consuming and sometimes unethical, observational studies are frequently used to study causal associations. In these studies, imbalance, or confounding, is usually controlled with multiple regression, which entails strong assumptions. The purpose of this manuscript is to describe strengths and weaknesses of several methods to control for confounding in observational studies, and to demonstrate their use in cross-sectional dataset that use patient registration data from the Juan Pablo II Primary Care Clinic in La Pintana-Chile. The dataset contains responses from 5855 families who provided complete information on family socio-demographics, family functioning and health problems among their family members. We employ regression adjustment, stratification, restriction, matching, propensity score matching, standardisation and inverse probability weighting to illustrate the approaches to better causal inference in non-experimental data and compare results. By applying study design and data analysis techniques that control for confounding in different ways than regression adjustment, researchers may strengthen the scientific relevance of observational studies. © 2016 International Union of Psychological Science.

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.

Construct Relevant and Irrelevant Variables in Math Problem Solving Assessment

ERIC Educational Resources Information Center

Birk, Lisa E.

2013-01-01

In this study, I examined the relation between various construct relevant and irrelevant variables and a math problem solving assessment. I used independent performance measures representing the variables of mathematics content knowledge, general ability, and reading fluency. Non-performance variables included gender, socioeconomic status,…

Insomnia Severity, Subjective Sleep Quality, and Risk for Obstructive Sleep Apnea in Veterans With Gulf War Illness.

PubMed

Chao, Linda L; Abadjian, Linda R; Esparza, Iva L; Reeb, Rosemary

2016-09-01

Despite the fact that sleep disturbances are common in veterans with Gulf War Illness (GWI), there has been a paucity of published sleep studies in this veteran population to date. Therefore, the present study examined subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia severity (assessed with the Insomnia Severity Index), and risk for obstructive sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans. Veterans with GWI, defined either by the Kansas or Centers for Disease Control and Prevention criteria, had greater risk for obstructive sleep apnea (i.e., higher STOP scores) than veterans without GWI. This difference persisted even after accounting for potentially confounding demographic (e.g., age, gender) and clinical variables. Veterans with GWI, defined by either the Kansas or Centers for Disease Control and Prevention criteria, also had significantly greater insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05), even after accounting for potentially confounding variables. Furthermore, there were significant, positive correlations between insomnia severity, subjective sleep quality, and GWI symptom severity (p ≤ 0.01). In stepwise linear regression models, insomnia severity significantly predicted GWI status over and above demographic and clinical variables. Together these findings provide good rationale for treating sleep disturbances in the management of GWI. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Coping strategies and quality of life in caregivers of dependent elderly relatives.

PubMed

Rodríguez-Pérez, Margarita; Abreu-Sánchez, Ana; Rojas-Ocaña, María Jesús; Del-Pino-Casado, Rafael

2017-04-14

Despite the importance of coping in caregiving, there are few studies on the relationship between coping and quality of life in caregivers of the frail dependent elderly. Thus, this study aims to analyze the relationship between coping strategies and quality of life dimensions in primary caregivers of dependent elderly relatives. A cross-sectional study was conducted from 86 caregivers. Predictive variables were coping strategies (problem-focused, emotion-focused, socially-supported, and dysfunctional); dependent variables were quality of life dimensions (psychological, physical, relational, and environmental); and potential confounding variables were age, gender, perceived health and burden of caregiver, and functional capacity of care receiver. Correlation coefficients were calculated and multiple linear regression analysis was performed. After controlling for potential confounders, dysfunctional coping was related to worse quality of life in the psychological dimension, while emotion-focused and socially-supported coping were related to superior psychological and environmental dimensions of quality of life. The physical and relational dimensions of quality of life were not related to coping strategies. 1) it is important to consider coping strategies in the assessment of primary caregivers of dependent elderly relatives; 2) the quality of life of caregivers is related to their coping strategies, 3) their quality of life can be worsened by avoidance-type coping, and 4) their quality of life can be improved by active emotion-focused coping and socially-supported coping.

Covariate selection with group lasso and doubly robust estimation of causal effects

PubMed Central

Koch, Brandon; Vock, David M.; Wolfson, Julian

2017-01-01

Summary The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this paper, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry. PMID:28636276

Covariate selection with group lasso and doubly robust estimation of causal effects.

PubMed

Koch, Brandon; Vock, David M; Wolfson, Julian

2018-03-01

The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this article, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry. © 2017, The International Biometric Society.

The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials.

PubMed

Hamley, Steven

2017-05-19

A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10). Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.

Complex Causal Process Diagrams for Analyzing the Health Impacts of Policy Interventions

PubMed Central

Joffe, Michael; Mindell, Jennifer

2006-01-01

Causal diagrams are rigorous tools for controlling confounding. They also can be used to describe complex causal systems, which is done routinely in communicable disease epidemiology. The use of change diagrams has advantages over static diagrams, because change diagrams are more tractable, relate better to interventions, and have clearer interpretations. Causal diagrams are a useful basis for modeling. They make assumptions explicit, provide a framework for analysis, generate testable predictions, explore the effects of interventions, and identify data gaps. Causal diagrams can be used to integrate different types of information and to facilitate communication both among public health experts and between public health experts and experts in other fields. Causal diagrams allow the use of instrumental variables, which can help control confounding and reverse causation. PMID:16449586

Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age--IPD meta-analysis of 4 large clinical trials.

PubMed

Beyerlein, Andreas; Hadders-Algra, Mijna; Kennedy, Katherine; Fewtrell, Mary; Singhal, Atul; Rosenfeld, Eva; Lucas, Alan; Bouwstra, Hylco; Koletzko, Berthold; von Kries, Rüdiger

2010-01-01

To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively. These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.

The Association Between School Bonding and Smoking Amongst Chilean Adolescents.

PubMed

Gaete, Jorge; Montgomery, Alan; Araya, Ricardo

2015-01-01

The objective of the research was to study the association between school bonding dimensions (school commitment and school attachment) and current adolescent smoking in Chile, controlling for confounding variables using the fifth Chilean School Population National Substance Use Survey, 2003 (CHSS-2003) data set. The CHSS-2003 is a stratified cross-sectional survey that gathers information about personal, familial, peer, and school factors and cigarette use using a self-reported questionnaire. Complete data from 21,956 adolescent students for all the variables of interest were used in the analyses. An exploratory factor analysis (EFA) was performed in order to explore the construct validity of the questionnaire and create the main exposure and potential confounding variables. Multivariable logistic regression analyses were undertaken to study the association between school bonding and smoking. The construct validity of the school attachment and school commitment scales was mainly supported by the EFA. Multivariable analyses showed strong evidence that, after adjusting for factors from different domains, school commitment (student's good grades and school attendance) appears to have a clear inverse association with current smoking (odds ratio [OR]=0.46, 95% confidence interval [CI]: 0.38-0.56). On the other hand, school attachment (their feelings towards their school and their teachers) was not associated with adolescent smoking (OR=1.16, 95% CI: 0.88-1.53). School commitment was strongly associated with current smoking. It is important to further study this variable with the aim of ascertaining whether or not interventions that improve school commitment may prevent or reduce smoking amongst adolescent students.

Socioeconomic position, psychosocial work environment and disability in an ageing workforce: a longitudinal analysis of SHARE data from 11 European countries.

PubMed

Reinhardt, Jan D; Wahrendorf, Morten; Siegrist, Johannes

2013-03-01

Prevention of disability in the ageing workforce is essential for sustaining economic growth in Europe. In order to provide information on entry points for preventive measures, it is important to better understand sociodemographic, socioeconomic and work-related determinants of disability in older employees. We aimed to test the hypothesis that low socioeconomic position and exposure to a stressful psychosocial work environment at baseline contribute to later disability. We further assumed that the association of socioeconomic position with disability is partly mediated by exposure to adverse working conditions. We studied longitudinal data from the first two waves of the Survey on Health, Ageing and Retirement in Europe comprising 11 European countries. Sociodemographic, socioeconomic and work-related factors (low control, effort-reward imbalance) and baseline disability of 2665 male and 2209 female employees aged between 50 and 64 years were used to predict disability 2 years later. Following the International Classification of Functioning (ICF), disability was subdivided into the components 'impairment' and 'restriction in activities and participation'. Two multilevel Poisson regressions were fitted to the data. After adjusting for baseline disability and relevant confounding variables, low socioeconomic position and chronic stress at work exerted significant effects on disability scores 2 years later. We found some support for the hypothesis that the association of socioeconomic position with disability is partly mediated by work stress. Investing in reduction of work stress and reducing social inequalities in health functioning are relevant entry points of policies that aim at maintaining work ability in early old age.

Weather conditions: a neglected factor in human salivary cortisol research?

NASA Astrophysics Data System (ADS)

Milas, Goran; Šupe-Domić, Daniela; Drmić-Hofman, Irena; Rumora, Lada; Klarić, Irena Martinović

2018-02-01

There is ample evidence that environmental stressors such as extreme weather conditions affect animal behavior and that this process is in part mediated through the elevated activity of the hypothalamic pituitary adrenal axis which results in an increase in cortisol secretion. This relationship has not been extensively researched in humans, and weather conditions have not been analyzed as a potential confounder in human studies of stress. Consequently, the goal of this paper was to assess the relationship between salivary cortisol and weather conditions in the course of everyday life and to test a possible moderating effect of two weather-related variables, the climate region and timing of exposure to outdoors conditions. The sample consisted of 903 secondary school students aged 18 to 21 years from Mediterranean and Continental regions. Cortisol from saliva was sampled in naturalistic settings at three time points over the course of a single day. We found that weather conditions are related to salivary cortisol concentration and that this relationship may be moderated by both the specific climate and the anticipation of immediate exposure to outdoors conditions. Unpleasant weather conditions are predictive for the level of salivary cortisol, but only among individuals who anticipate being exposed to it in the immediate future (e.g., in students attending school in the morning shift). We also demonstrated that isolated weather conditions or their patterns may be relevant in one climate area (e.g., Continental) while less relevant in the other (e.g., Mediterranean). Results of this study draw attention to the importance of controlling weather conditions in human salivary cortisol research.

Prevalence of clinically relevant muscle weakness and its association with vitamin D status among older adults in Ecuador.

PubMed

Orces, Carlos H

2017-10-01

Muscle weakness and 25-hydroxyvitamin D (25(OH)D) deficiency have been associated with adverse outcomes among older adults. However, little is known about the relationship between clinically relevant muscle weakness and 25(OH)D levels in Ecuador. To examine the prevalence of muscle weakness and its association with 25(OH)D status among subjects aged 60 years and older in Ecuador. The present study was based on data from 2205 participants in the first National Survey of Health, Wellbeing, and Aging. The Foundation for the National Institute of Health Sarcopenia Project criteria was used to examine muscle weakness prevalence rates. Gender-specific general linear and logistic regression models adjusted for potential confounders were created to compare mean 25(OH)D concentrations and 25(OH)D deficiency across muscle strength categories, respectively. An estimated 32.2% of women and 33.4% of men had evidence of clinically relevant muscle weakness in Ecuador. In general, increased muscle weakness prevalence rates were present among Indigenous, residents in the rural Andes Mountains, underweight subjects, and those with a sedentary lifestyle. Muscle strength was significantly and directly correlated with mean 25(OH)D levels. After controlling for potential confounders, 25(OH)D deficiency prevalence rates were 31 and 43% higher among men and women with muscle weakness than those with normal strength, respectively. One-third of older adults nationwide had evidence of muscle weakness. While the present study found a significant correlation between muscle strength and 25(OH)D concentrations, further research is needed to examine whether optimizing 25(OH)D levels may improve muscle weakness among older adults.

Epigenetic Patterns of PTSD: DNA Methylation In Serum of OIF/OEF Servicemembers

DTIC Science & Technology

2011-01-01

ascertained via query of the International Classification of Diseases , 9th Revision (ICD-9) codes 290-320. To attempt to control for confounding by other...other CNS tissues is not clear. Although relevant to a different class of disease , many of the aberrations that have been detected in the DNA of...valuable diagnostic tool in various diseases . (50-53) Compared with cultured cells, clinical specimens, such as whole blood, serum, and even brain

Evidence for a neural correlate of a framing effect: bias-specific activity in the ventromedial prefrontal cortex during credibility judgments.

PubMed

Deppe, M; Schwindt, W; Krämer, J; Kugel, H; Plassmann, H; Kenning, P; Ringelstein, E B

2005-11-15

Neural processes within the medial prefrontal cortex play a crucial role in assessing and integrating emotional and other implicit information during decision-making. Phylogenetically, it was important for the individual to assess the relevance of all kinds of environmental stimuli in order to adapt behavior in a flexible manner. Consequently, we can in principle not exclude that environmental information covertly influences the evaluation of actually decision relevant facts ("framing effect"). To test the hypothesis that the medial prefrontal cortex is involved into a framing effect we employed functional magnetic resonance imaging (fMRI) during a binary credibility judgment task. Twenty-one subjects were asked to judge 30 normalized news magazine headlines by forced answers as "true" or "false". To confound the judgments by formally irrelevant framing information we presented each of the headlines in four different news magazines characterized by varying credibility. For each subject the susceptibility to the judgment confounder (framing information) was assessed by magazine-specific modifications of the answers given. We could show that individual activity changes of the ventromedial prefrontal cortex during the judgments correlate with the degree of an individual's susceptibility to the framing information. We found (i) a neural correlate of a framing effect as postulated by behavioral decision theorists that (ii) reflects interindividual differences in the degree of the susceptibility to framing information.

Physical health-related quality of life in relation to metabolic health and obesity among men and women in Germany.

PubMed

Truthmann, Julia; Mensink, Gert B M; Bosy-Westphal, Anja; Hapke, Ulfert; Scheidt-Nave, Christa; Schienkiewitz, Anja

2017-06-10

This study examined sex-specific differences in physical health-related quality of life (HRQoL) across subgroups of metabolic health and obesity. We specifically asked whether (1) obesity is related to lower HRQoL independent of metabolic health status and potential confounders, and (2) whether associations are similar in men and women. We used cross-sectional data from the German Health Interview and Examination Survey 2008-11. Physical HRQoL was measured using the Short Form-36 version 2 physical component summary (PCS) score. Based on harmonized ATPIII criteria for the definition of the metabolic health and a body mass index ≥ 30 kg/m 2 to define obesity, individuals were classified as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Sex-specific analyses including multivariable linear regression analyses were based on PCS as the dependent variable, metabolic health and obesity category as the independent variable with three categories and MHNO as the reference, and age, education, lifestyle and comorbidities as confounders. This study included 6860 participants (3298 men, 3562 women). Compared to MHNO, all other metabolic health and obesity categories had significantly lower PCS in both sexes. As reflected by the beta coefficients [95% confidence interval] from bivariable linear regression models, a significant inverse association with PCS was strongest for MUO (men: -7.0 [-8.2; -5.8]; women: -9.0 [-10.2; -7.9]), intermediate for MUNO (men: -4.2 [-5.3; -3.1]; women: -5.6 [-6.8; -4.4]) and least pronounced for MHO (men: -2.2 [-3.6; -0.8]; women -3.9 [-5.4; -2.5]). Differences in relation to MHNO remained statistically significant for all groups after adjusting for confounders, but decreased in particular for MUNO (men:-1.3 [-2.3; -0.3]; women: -1.5 [-2.7; -0.3]. Obesity was significantly related to lower physical HRQoL, independent of metabolic health status. Potential confounders including age, educational status, health-related behaviors, and comorbidities explained parts of the inverse relationship. Associations were evident in both sexes and consistently more pronounced among women than men.

Simpson's Paradox and Confounding Factors in University Rankings: A Demonstration Using QS 2011-12 Data

ERIC Educational Resources Information Center

Soh, Kay Cheng

2012-01-01

University ranking has become ritualistic in higher education. Ranking results are taken as bona fide by rank users. Ranking systems usually use large data sets from highly heterogeneous universities of varied backgrounds. This poses the problem of Simpson's Paradox and the lurking variables causing it. Using QS 2011-2012 Ranking data, the dual…

Maternal Pre-Pregnancy Body Mass Index and Offspring Temperament and Behavior at 1 and 2 Years of Age

ERIC Educational Resources Information Center

Van Lieshout, Ryan J.; Schmidt, Louis A.; Robinson, Monique; Niccols, Alison; Boyle, Michael H.

2013-01-01

Recent research suggests that fetal exposure to increased maternal body mass index (BMI) during pregnancy may be associated with psychopathology later in life. When this link first emerges, and if it is due to intrauterine exposures or confounding variables is not known. We therefore assessed associations between maternal pre-pregnancy BMI and:…

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…

Reduced streamflow lowers dry-season growth of rainbow trout in a small stream

Treesearch

Bret C. Harvey; Rodney J. Nakamoto; Jason L. White

2006-01-01

A wide variety of resource management activities can affect surface discharge in small streams. Often, the effects of variation in streamflow on fish survival and growth can be difficult to estimate because of possible confounding with the effects of other variables, such as water temperature and fish density. We measured the effect of streamflow on survival and growth...

Individual tree differences confound effects of growth regulators in rooting sugar maple softwood cuttings

Treesearch

John R. Donnelly

1971-01-01

Softwood stem cuttings from three mature sugar maple trees were treated with several types and concentrations of growth regulators. Lack of statistical significance was due to extreme variability in tree response: low levels of auxin stimulated rooting in two study trees, while auxins inhibited rooting in the other tree. It is postulated that variations in rooting...

The Chabot Emotional Differentiation Scale: A Theoretically and Psychometrically Sound Instrument for Measuring Bowen's Intrapsychic Aspect of Differentiation

ERIC Educational Resources Information Center

Licht, Carolyn; Chabot, David

2006-01-01

Bowen's theory (1978) of differentiation is the personality variable most critical to mature development and the attainment of psychological health. The study of psychological differentiation has been confounded by confusion regarding the constructs being studied and the measurement tools used to assess them. The purpose of this review is to…

Measuring the wetting angle and perimeter of single wood pulp fibers : a modified method

Treesearch

John H. Klungness

1981-01-01

In pulp processing development it is often necessary to measure the effect of a process variable on individual pulp fiber wettability. Such processes would include drying of market pulps, recycling of secondary fibers, and surface modification of fibers as in sizing. However, if wettability is measured on a fiber sheet surface, the results are confounded by...

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…

Class-Size Reduction: Using What's Been Learned To Inform Educational Decisions. The Informed Educator Series.

ERIC Educational Resources Information Center

Boniface, Russell; Protheroe, Nancy

Class-size reduction (CSR) has been a complex and contentious issue for the last quarter century. Although the small-class concept was adopted because it appealed to common sense, research over time has revealed a mix of confounding variables, instead of a definitive conclusion. Some CSR efforts, such as Tennessee's Project STAR and Wisconsin's…

Uncovering noisy social signals: Using optimization methods from experimental physics to study social phenomena.

PubMed

Kaptein, Maurits; van Emden, Robin; Iannuzzi, Davide

2017-01-01

Due to the ubiquitous presence of treatment heterogeneity, measurement error, and contextual confounders, numerous social phenomena are hard to study. Precise control of treatment variables and possible confounders is often key to the success of studies in the social sciences, yet often proves out of the realm of control of the experimenter. To amend this situation we propose a novel approach coined "lock-in feedback" which is based on a method that is routinely used in high-precision physics experiments to extract small signals out of a noisy environment. Here, we adapt the method to noisy social signals in multiple dimensions and evaluate it by studying an inherently noisy topic: the perception of (subjective) beauty. We show that the lock-in feedback approach allows one to select optimal treatment levels despite the presence of considerable noise. Furthermore, through the introduction of an external contextual shock we demonstrate that we can find relationships between noisy variables that were hitherto unknown. We therefore argue that lock-in methods may provide a valuable addition to the social scientist's experimental toolbox and we explicitly discuss a number of future applications.

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.

The influence of depression on personality traits in patients with fibromyalgia: a case-control study.

PubMed

Santos, Daniela M; Lage, Laís V; Jabur, Eleonora K; Kaziyama, Helena H S; Iosifescu, Dan V; De Lucia, Mara Cristina S; Fráguas, Renério

2017-01-01

We developed this study to investigate the association of fibromyalgia with personality traits, controlling for depression and other potential confounders. We assessed personality traits using the Cloninger's Temperament and Character Inventory (TCI) in 78 female patients with fibromyalgia and in a control group of 78 subjects without fibromyalgia. The Mini-International Neuropsychiatric Interview was used to assess depression and anxiety diagnoses. To investigate the association between fibromyalgia and the Cloninger's Temperament and Character Inventory we performed unadjusted and adjusted analyses of covariance, using the TCI score as dependent variable and adjusting the model for depression, anxiety and for clinical and socio-demographic variables. We used a backward selection method to choose the final model. In the unadjusted analysis, fibromyalgia was associated with all personality traits, except persistency. After adjusting for depression and anxiety, patients with fibromyalgia presented decreased novelty seeking compared to controls; the differences in other personality traits were no longer significant. Novelty seeking was also correlated with the length of history of fibromyalgia and pain intensity. Decreased novelty seeking may be a personality trait associated with fibromyalgia. Depression and anxiety should be considered potential confounders in the evaluation of personality traits in this population.

Uncovering noisy social signals: Using optimization methods from experimental physics to study social phenomena

PubMed Central

2017-01-01

Due to the ubiquitous presence of treatment heterogeneity, measurement error, and contextual confounders, numerous social phenomena are hard to study. Precise control of treatment variables and possible confounders is often key to the success of studies in the social sciences, yet often proves out of the realm of control of the experimenter. To amend this situation we propose a novel approach coined “lock-in feedback” which is based on a method that is routinely used in high-precision physics experiments to extract small signals out of a noisy environment. Here, we adapt the method to noisy social signals in multiple dimensions and evaluate it by studying an inherently noisy topic: the perception of (subjective) beauty. We show that the lock-in feedback approach allows one to select optimal treatment levels despite the presence of considerable noise. Furthermore, through the introduction of an external contextual shock we demonstrate that we can find relationships between noisy variables that were hitherto unknown. We therefore argue that lock-in methods may provide a valuable addition to the social scientist’s experimental toolbox and we explicitly discuss a number of future applications. PMID:28306728

Factors Associated with Hepatitis C Knowledge Before and After an Educational Intervention among Vietnamese Americans

PubMed Central

Lee, Sunmin; Zhai, Shumenghui; Zhang, Guo (Yolanda); Ma, Xiang S; Lu, Xiaoxiao; Tan, Yin; Siu, Philip; Seals, Brenda; Ma, Grace X

2015-01-01

BACKGROUND Hepatitis C virus (HCV) is a major cause of chronic liver disease and cancer. Vietnamese Americans are at high risk of HCV infection, with men having the highest US incidence of liver cancer. This study examines an intervention to improve HCV knowledge among Vietnamese Americans. STUDY Seven Vietnamese community-based organizations in Pennsylvania and New Jersey recruited a total of 306 Vietnamese participants from 2010 to 2011. RESULTS Average knowledge scores for pretest and posttest were 3.32 and 5.88, respectively (maximum 10). After adjusting for confounding variables, age and higher education were positively associated with higher pretest scores and having a physician who spoke English or Vietnamese was negatively associated with higher pretest scores. Additionally, after adjusting for confounding variables, household income, education, and having an HCV-infected family member significantly increased knowledge scores. CONCLUSIONS Promotion and development of HCV educational programs can increase HCV knowledge among race and ethnic groups, such as Vietnamese Americans. Giving timely information to at-risk groups provides the opportunity to correct misconceptions, decrease HCV risk behaviors, and encourage testing that might improve timely HCV diagnosis and treatment. PMID:26561280

Genetic Instrumental Variable Studies of Effects of Prenatal Risk Factors

PubMed Central

von Hinke Kessler Scholder, Stephanie

2013-01-01

Identifying the effects of maternal risk factors during pregnancy on infant and child health is an area of tremendous research interest. However, of interest to policy makers is unraveling the causal effects of prenatal risk factors, not their associations with child health, which may be confounded by several unobserved factors. In this paper, we evaluate the utility of genetic variants in three genes that have unequivocal evidence of being related to three major risk factors – CHRNA3 for smoking, ADH1B for alcohol use, and FTO for obesity – as instrumental variables for identifying the causal effects of such factors during pregnancy. Using two independent datasets, we find that these variants are overall predictive of the risk factors and are not systematically related to observed confounders, suggesting that they may be useful instruments. We also find some suggestive evidence that genetic effects are stronger during than before pregnancy. We provide an empirical example illustrating the use of these genetic variants as instruments to evaluate the effects of risk factors on birth weight. Finally, we offer suggestions for researchers contemplating the use of these variants as instruments. PMID:23701534

Supervisor Autonomy and Considerate Leadership Style are Associated with Supervisors’ Likelihood to Accommodate Back Injured Workers

PubMed Central

McGuire, Connor; Kristman, Vicki L; Williams-Whitt, Kelly; Reguly, Paula; Shaw, William; Soklaridis, Sophie

2015-01-01

PURPOSE To determine the association between supervisors’ leadership style and autonomy and supervisors’ likelihood of supporting job accommodations for back-injured workers. METHODS A cross-sectional study of supervisors from Canadian and US employers was conducted using a web-based, self-report questionnaire that included a case vignette of a back-injured worker. Autonomy and two dimensions of leadership style (considerate and initiating structure) were included as exposures. The outcome, supervisors’ likeliness to support job accommodation, was measured with the Job Accommodation Scale. We conducted univariate analyses of all variables and bivariate analyses of the JAS score with each exposure and potential confounding factor. We used multivariable generalized linear models to control for confounding factors. RESULTS A total of 796 supervisors participated. Considerate leadership style (β= .012; 95% CI: .009–.016) and autonomy (β= .066; 95% CI: .025–.11) were positively associated with supervisors’ likelihood to accommodate after adjusting for appropriate confounding factors. An initiating structure leadership style was not significantly associated with supervisors’ likelihood to accommodate (β = .0018; 95% CI: −.0026–.0061) after adjusting for appropriate confounders. CONCLUSIONS Autonomy and a considerate leadership style were positively associated with supervisors’ likelihood to accommodate a back-injured worker. Providing supervisors with more autonomy over decisions of accommodation and developing their considerate leadership style may aid in increasing work accommodation for back-injured workers and preventing prolonged work disability. PMID:25595332

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.

A robust bayesian estimate of the concordance correlation coefficient.

PubMed

Feng, Dai; Baumgartner, Richard; Svetnik, Vladimir

2015-01-01

A need for assessment of agreement arises in many situations including statistical biomarker qualification or assay or method validation. Concordance correlation coefficient (CCC) is one of the most popular scaled indices reported in evaluation of agreement. Robust methods for CCC estimation currently present an important statistical challenge. Here, we propose a novel Bayesian method of robust estimation of CCC based on multivariate Student's t-distribution and compare it with its alternatives. Furthermore, we extend the method to practically relevant settings, enabling incorporation of confounding covariates and replications. The superiority of the new approach is demonstrated using simulation as well as real datasets from biomarker application in electroencephalography (EEG). This biomarker is relevant in neuroscience for development of treatments for insomnia.

Elevated risk of incarceration among street-involved youth who initiate drug dealing.

PubMed

Hoy, Carly; Barker, Brittany; Regan, Jackie; Dong, Huiru; Richardson, Lindsey; Kerr, Thomas; DeBeck, Kora

2016-11-22

Street-involved youth are known to be an economically vulnerable population that commonly resorts to risky activities such as drug dealing to generate income. While incarceration is common among people who use illicit drugs and associated with increased economic vulnerability, interventions among this population remain inadequate. Although previous research has documented the role of incarceration in further entrenching youth in both the criminal justice system and street life, less is known whether recent incarceration predicts initiating drug dealing among vulnerable youth. This study examines the relationship between incarceration and drug dealing initiation among street-involved youth. Between September 2005 and November 2014, data were collected through the At-Risk Youth Study, a cohort of street-involved youth who use illicit drugs, in Vancouver, Canada. An extended Cox model with time-dependent variables was used to examine the relationship between recent incarceration and initiation into drug dealing, controlling for relevant confounders. Among 1172 youth enrolled, only 194 (16.6%) were drug dealing naïve at baseline and completed at least one additional study visit to facilitate the assessment of drug dealing initiation. Among this sample, 56 (29%) subsequently initiated drug dealing. In final multivariable Cox regression analysis, recent incarceration was significantly associated with initiating drug dealing (adjusted hazard ratio = 2.31; 95% confidence interval (CI) 1.21-4.42), after adjusting for potential confounders. Measures of recent incarceration lagged to the prior study follow-up were not found to predict initiation of drug dealing (hazard ratio = 1.50; 95% CI 0.66-3.42). These findings suggest that among this study sample, incarceration does not appear to significantly propel youth to initiate drug dealing. However, the initiation of drug dealing among youth coincides with an increased risk of incarceration and their consequent vulnerability to the significant harms associated therein. Given that existing services tailored to street-involved youth are inadequate, evidence-based interventions should be invested and scaled up as a public health priority.

The Influence of Hospital Volume on Circumferential Resection Margin Involvement: Results of the Dutch Surgical Colorectal Audit.

PubMed

Gietelink, Lieke; Henneman, Daniel; van Leersum, Nicoline J; de Noo, Mirre; Manusama, Eric; Tanis, Pieter J; Tollenaar, Rob A E M; Wouters, Michel W J M

2016-04-01

This population-based study evaluates the association between hospital volume and CRM (circumferential resection margin) involvement, adjusted for other confounders, in rectal cancer surgery. A low hospital volume (<20 cases/year) was independently associated with a higher risk of CRM involvement (odds ratio=1.54; 95% CI: 1.12-2.11). To evaluate the association between hospital volume and CRM (circumferential resection margin) involvement in rectal cancer surgery. To guarantee the quality of surgical treatment of rectal cancer, the Association of Surgeons of the Netherlands has stated a minimal annual volume standard of 20 procedures per hospital. The influence of hospital volume has been examined for different outcome variables in rectal cancer surgery. Its influence on the pathological outcome (CRM) however remains unclear. As long-term outcomes are best predicted by the CRM status, this parameter is of essential importance in the debate on the justification of minimal volume standards in rectal cancer surgery. Data from the Dutch Surgical Colorectal Audit (2011-2012) were used. Hospital volume was divided into 3 groups, and baseline characteristics were described. The influence of hospital volume on CRM involvement was analyzed, in a multivariate model, between low- and high-volume hospitals, according to the minimal volume standards. This study included 5161 patients. CRM was recorded in 86% of patients. CRM involvement was 11% in low-volume group versus 7.7% and 7.9% in the medium- and high-volume group (P≤0.001). After adjustment for relevant confounders, the influence of hospital volume on CRM involvement was still significant odds ratio (OR) = 1.54; 95% CI: 1.12-2.11). The outcomes of this pooled analysis support minimal volume standards in rectal cancer surgery. Low hospital volume was independently associated with a higher risk of CRM involvement (OR = 1.54; 95% CI: 1.12-2.11).

Case-control vaccine effectiveness studies: Data collection, analysis and reporting results.

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

The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a 'real world' context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies. Published by Elsevier Ltd.

Reporting of methodological features in observational studies of pre-harvest food safety.

PubMed

Sargeant, Jan M; O'Connor, Annette M; Renter, David G; Kelton, David F; Snedeker, Kate; Wisener, Lee V; Leonard, Erin K; Guthrie, Alessia D; Faires, Meredith

2011-02-01

Observational studies in pre-harvest food safety may be useful for identifying risk factors and for evaluating potential mitigation strategies to reduce foodborne pathogens. However, there are no structured reporting guidelines for these types of study designs in livestock species. Our objective was to evaluate the reporting of observational studies in the pre-harvest food safety literature using guidelines modified from the human healthcare literature. We identified 100 pre-harvest food safety studies published between 1999 and 2009. Each study was evaluated independently by two reviewers using a structured checklist. Of the 38 studies that explicitly stated the observational study design, 27 were described as cross-sectional studies, eight as case-control studies, and three as cohort studies. Study features reported in over 75% of the selected studies included: description of the geographic location of the studies, definitions and sources of data for outcomes, organizational level and source of data for independent variables, description of statistical methods and results, number of herds enrolled in the study and included in the analysis, and sources of study funding. However, other features were not consistently reported, including details related to eligibility criteria for groups (such as barn, room, or pen) and individuals, numbers of groups and individuals included in various stages of the study, identification of primary outcomes, the distinction between putative risk factors and confounding variables, the identification of a primary exposure variable, the referent level for evaluation of categorical variable associations, methods of controlling confounding variables and missing variables, model fit, details of subset analysis, demographic information at the sampling unit level, and generalizability of the study results. Improvement in reporting of observational studies of pre-harvest food safety will aid research readers and reviewers in interpreting and evaluating the results of such studies. Copyright © 2010 Elsevier B.V. All rights reserved.

A community study on emotional distress among Arab and Jewish Israelis over the age of 60.

PubMed

Shemesh, Annarosa Anat; Kohn, Robert; Blumstein, Tzvia; Geraisy, Nabil; Novikov, Ilya; Levav, Itzhak

2006-01-01

The elderly constitute a vulnerable group for psychopathology, yet research on their mental health among both Arab and Jews in Israel remains limited. The same is the case in Arab countries. This paper reports on the contrasting distribution of the mean emotional distress (ED) scores and rates of suspected clinical cases, and their related risk factors, among community residents over the age of 60. Several national agencies conducted a survey on 5,055 elderly individuals to investigate their health status, including ED. The interview included socio-demographic and behavioral health items, as well as a modified 12 item-GHQ as a measure of ED. Total ED scores and prevalence rates for suspected psychopathology were calculated. Their respective risk factors were examined using univariate and multivariate methods. The ED scores were highest among Muslim Arabs (4.9), followed by Christian Arabs (4.2), Jews (3.1) and Druzes (2.8). Their estimated prevalence rates were 43.4%, 37.0%, 21.4%, and 17.0%, respectively. The gradient of these results remained unchanged in the multivariate analysis for ED scores adjusting for confounding variables. In contrast, logistic regression analysis controlling for confounding variables did not find a differential risk for suspected psychopathology between Arabs and Jews. Conceivably, the higher demoralization scores among elderly Arabs are associated with their minority status affiliation, as well as with the rapid social changes that have taken place in their midst. A cultural response style may be entertained as a possible explanation. However, these factors do not impact the risk for suspected psychopathology where no differential risk was noted after adjustments for confounders. Copyright 2005 John Wiley & Sons, Ltd.

Accounting for Time-Varying Confounding in the Relationship Between Obesity and Coronary Heart Disease: Analysis With G-Estimation: The ARIC Study.

PubMed

Shakiba, Maryam; Mansournia, Mohammad Ali; Salari, Arsalan; Soori, Hamid; Mansournia, Nasrin; Kaufman, Jay S

2018-06-01

In longitudinal studies, standard analysis may yield biased estimates of exposure effect in the presence of time-varying confounders that are also intermediate variables. We aimed to quantify the relationship between obesity and coronary heart disease (CHD) by appropriately adjusting for time-varying confounders. This study was performed in a subset of participants from the Atherosclerosis Risk in Communities (ARIC) Study (1987-2010), a US study designed to investigate risk factors for atherosclerosis. General obesity was defined as body mass index (weight (kg)/height (m)2) ≥30, and abdominal obesity (AOB) was defined according to either waist circumference (≥102 cm in men and ≥88 cm in women) or waist:hip ratio (≥0.9 in men and ≥0.85 in women). The association of obesity with CHD was estimated by G-estimation and compared with results from accelerated failure-time models using 3 specifications. The first model, which adjusted for baseline covariates, excluding metabolic mediators of obesity, showed increased risk of CHD for all obesity measures. Further adjustment for metabolic mediators in the second model and time-varying variables in the third model produced negligible changes in the hazard ratios. The hazard ratios estimated by G-estimation were 1.15 (95% confidence interval (CI): 0.83, 1.47) for general obesity, 1.65 (95% CI: 1.35, 1.92) for AOB based on waist circumference, and 1.38 (95% CI: 1.13, 1.99) for AOB based on waist:hip ratio, suggesting that AOB increased the risk of CHD. The G-estimated hazard ratios for both measures were further from the null than those derived from standard models.

The role of job strain in understanding midlife common mental disorder: a national birth cohort study.

PubMed

Harvey, Samuel B; Sellahewa, Dilan A; Wang, Min-Jung; Milligan-Saville, Josie; Bryan, Bridget T; Henderson, Max; Hatch, Stephani L; Mykletun, Arnstein

2018-06-01

Long-standing concerns exist about reverse causation and residual confounding in the prospective association between job strain and risk of future common mental disorders. We aimed to address these concerns through analysis of data collected in the UK National Child Development Study, a large British cohort study. Data from the National Child Development Study (n=6870) were analysed by use of multivariate logistic regression to investigate the prospective association between job strain variables at age 45 years and risk of future common mental disorders at age 50 years, controlling for lifetime psychiatric history and a range of other possible confounding variables across the lifecourse. Population attributable fractions were calculated to estimate the public health effect of job strain on midlife mental health. In the final model, adjusted for all measured confounders, high job demands (odds ratio 1·70, 95% CI 1·25-2·32; p=0·0008), low job control (1·89, 1·29-2·77; p=0·0010), and high job strain (2·22, 1·59-3·09; p<0·0001) remained significant independent predictors of future onset of common mental disorder. If causality is assumed, our findings suggest that 14% of new cases of common mental disorder could have been prevented through elimination of high job strain (population attributable fraction 0·14, 0·06-0·20). High job strain appears to independently affect the risk of future common mental disorders in midlife. These findings suggest that modifiable work-related risk factors might be an important target in efforts to reduce the prevalence of common mental disorders. iCare Foundation and Mental Health Branch, NSW Health. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Cross-sectional analysis of food choice frequency, sleep confounding beverages, and psychological distress predictors of sleep quality.

PubMed

Knowlden, Adam P; Burns, Maranda; Harcrow, Andy; Shewmake, Meghan E

2016-03-16

Poor sleep quality is a significant public health problem. The role of nutrition in predicting sleep quality is a relatively unexplored area of inquiry. The purpose of this study was to evaluate the capacity of 10 food choice categories, sleep confounding beverages, and psychological distress to predict the sleep quality of college students. A logistic regression model comprising 10 food choice variables (healthy proteins, unhealthy proteins, healthy dairy, unhealthy dairy, healthy grains, unhealthy grains, healthy fruits and vegetables, unhealthy empty calories, healthy beverages, unhealthy beverages), sleep confounding beverages (caffeinated/alcoholic beverages), as well as psychological distress (low, moderate, serious distress) was computed to determine the capacity of the variables to predict sleep quality (good/poor). The odds of poor sleep quality were 32.4% lower for each unit of increased frequency of healthy proteins consumed (p<0.001; OR=0.676), 14.1% lower for each unit of increased frequency of healthy dairy food choices consumed (p=0.024; OR=0.859), 13.1% higher for each unit of increased frequency of empty calorie food choices consumed (p=0.003; OR=1.131), and 107.3% higher for those classified in the moderate psychological distress (p=0.016; OR=2.073). Collectively, healthy proteins, healthy dairy, unhealthy empty calories, and moderate psychological distress were moderately predictive of sleep quality in the sample (Nagelkerke R2=23.8%). Results of the study suggested higher frequency of consumption of healthy protein and healthy dairy food choices reduced the odds of poor sleep quality, while higher consumption of empty calories and moderate psychological distress increased the odds of poor sleep quality.

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.

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.

A Behavior Genetic Investigation of Adolescent Motherhood and Offspring Mental Health Problems

PubMed Central

Harden, K. Paige; Lynch, Stacy K.; Turkheimer, Eric; Emery, Robert E.; D’Onofrio, Brian M.; Slutske, Wendy S.; Waldron, Mary D.; Heath, Andrew C.; Statham, Dixie J.; Martin, Nicholas G.

2010-01-01

The present study examines the relations between adolescent motherhood and children’s behavior, substance use, and internalizing problems in a sample of 1,368 children of 712 female twins from Australia. Adolescent motherhood remained significantly associated with all mental health problems, even when using a quasiexperimental design capable of controlling for genetic and environmental confounds. However, the relation between adolescent motherhood and offspring behavior problems and substance use was partially confounded by family background variables that influence both generations. The results are consistent with a causal relation between adolescent motherhood and offspring mental health problems, and they highlight the usefulness of behavior genetic designs when examining putative environmental risks for the development of psychopathology. The generalizability of these results to the United States, which has a higher adolescent birth rate, is discussed. PMID:18020715

Alcohol consumption and ambulatory blood pressure: a community-based study in an elderly cohort.

PubMed

Jaubert, Marie-Perrine; Jin, Zhezhen; Russo, Cesare; Schwartz, Joseph E; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Sacco, Ralph L; Di Tullio, Marco R

2014-05-01

Although heavy alcohol consumption is associated with hypertension, the impact of lighter consumption on blood pressure (BP) is controversial. The protective effect of light alcohol consumption on cardiovascular disease described in previous studies could be, in part, mediated by effects of alcohol on BP. However, only a few studies investigating the association between alcohol and BP included elderly subjects, despite their higher risk of hypertension sequelae. Accordingly, we evaluated the relationship between alcohol consumption and 24-hour ambulatory BP in a community-based elderly cohort. Among the participants in the Cardiac Abnormalities and Brain Lesion study, 553 subjects (mean age = 70.6 ± 9.6 years) who underwent 24-hour ambulatory BP monitoring were examined. Alcohol consumption was categorized as (i) none (reference; <1 drink/month); (ii) very light consumption (1 drink/month to 1 drink/week); (iii) light consumption (2 drinks/week to 1 drink/day); (iv) moderate-to-heavy consumption (>1 drink/day). Former drinkers were excluded. After adjustment for relevant covariables, mean values of daytime diastolic BP (DBP), nighttime DBP, and 24-hour DBP were significantly higher in moderate-to-heavy drinkers than in the reference group, whereas systolic BP parameters were not significantly different across consumption groups. Daytime systolic BP and DBP variability (SD of the measurements) were significantly lower in very light drinkers than in the reference group, independent of potential confounders. Moderate-to-heavy alcohol consumption was associated with higher DBP values. Very light alcohol consumption was associated with reduced daytime BP variability. The latter association may contribute to the known beneficial cardiovascular effects of light alcohol consumption.

Ecological drivers of guanaco recruitment: variable carrying capacity and density dependence.

PubMed

Marino, Andrea; Pascual, Miguel; Baldi, Ricardo

2014-08-01

Ungulates living in predator-free reserves offer the opportunity to study the influence of food limitation on population dynamics without the potentially confounding effects of top-down regulation or livestock competition. We assessed the influence of relative forage availability and population density on guanaco recruitment in two predator-free reserves in eastern Patagonia, with contrasting scenarios of population density. We also explored the relative contribution of the observed recruitment to population growth using a deterministic linear model to test the assumption that the studied populations were closed units. The observed densities increased twice as fast as our theoretical populations, indicating that marked immigration has taken place during the recovery phase experienced by both populations, thus we rejected the closed-population assumption. Regarding the factors driving variation in recruitment, in the low- to medium-density setting, we found a positive linear relationship between recruitment and surrogates of annual primary production, whereas no density dependence was detected. In contrast, in the high-density scenario, both annual primary production and population density showed marked effects, indicating a positive relationship between recruitment and per capita food availability above a food-limitation threshold. Our results support the idea that environmental carrying capacity fluctuates in response to climatic variation, and that these fluctuations have relevant consequences for herbivore dynamics, such as amplifying density dependence in drier years. We conclude that including the coupling between environmental variability in resources and density dependence is crucial to model ungulate population dynamics; to overlook temporal changes in carrying capacity may even mask density dependence as well as other important processes.

Model building strategy for logistic regression: purposeful selection.

PubMed

Zhang, Zhongheng

2016-03-01

Logistic regression is one of the most commonly used models to account for confounders in medical literature. The article introduces how to perform purposeful selection model building strategy with R. I stress on the use of likelihood ratio test to see whether deleting a variable will have significant impact on model fit. A deleted variable should also be checked for whether it is an important adjustment of remaining covariates. Interaction should be checked to disentangle complex relationship between covariates and their synergistic effect on response variable. Model should be checked for the goodness-of-fit (GOF). In other words, how the fitted model reflects the real data. Hosmer-Lemeshow GOF test is the most widely used for logistic regression model.

Exploring heterogeneity in clinical trials with latent class analysis

PubMed Central

Abarda, Abdallah; Contractor, Ateka A.; Wang, Juan; Dayton, C. Mitchell

2018-01-01

Case-mix is common in clinical trials and treatment effect can vary across different subgroups. Conventionally, a subgroup analysis is performed by dividing the overall study population by one or two grouping variables. It is usually impossible to explore complex high-order intersections among confounding variables. Latent class analysis (LCA) provides a framework to identify latent classes by observed manifest variables. Distal clinical outcomes and treatment effect can be different across these classes. This paper provides a step-by-step tutorial on how to perform LCA with R. A simulated dataset is generated to illustrate the process. In the example, the classify-analyze approach is employed to explore the differential treatment effects on distal outcomes across latent classes. PMID:29955579

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.

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

Human punishment is not primarily motivated by inequality

PubMed Central

Marczyk, Jesse

2017-01-01

Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player’s payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value. PMID:28187166

Social work perspectives on human behavior.

PubMed

Wodarski, J S

1993-01-01

This manuscript addresses recent developments in human behavior research that are relevant to social work practice. Specific items addressed are biological aspects of behavior, life span development, cognitive variables, the self-efficacy learning process, the perceptual process, the exchange model, group level variables, macro level variables, and gender and ethnic-racial variables. Where relevant, specific applications to social work practice are provided.

Heart period variability and psychopathology in urban boys at risk for delinquency.

PubMed

Pine, D S; Wasserman, G A; Miller, L; Coplan, J D; Bagiella, E; Kovelenku, P; Myers, M M; Sloan, R P

1998-09-01

To examine associations between heart period variability (HPV) and psychopathology in young urban boys at risk for delinquency, a series of 697-11-year-old younger brothers of adjudicated delinquents received a standardized psychiatric evaluation and an assessment of heart period variability (HPV). Psychiatric symptoms were rated in two domains: externalizing and internalizing psychopathology. Continuous measures of both externalizing and internalizing psychopathology were associated with reductions in HPV components related to parasympathetic activity. These associations could not be explained by a number of potentially confounding variables, such as age, ethnicity, social class, body size, or family history of hypertension. Although familial hypertension predicted reduced HPV and externalizing psychopathology, associations between externalizing psychopathology and HPV were independent of familial hypertension. Psychiatric symptoms are associated with reduced HPV in young urban boys at risk for delinquency.

Land-use change and infectious disease in West Africa

NASA Astrophysics Data System (ADS)

Thomson, M. C.; Ericksen, P. J.; Mohamed, A. Ben; Connor, S. J.

Land-use change has been associated with changes in the dynamics of infectious disease in West Africa. Here we describe the complex interactions of land-use change with three diseases (both vector- and non-vector-borne) of considerable public health significance in this region, namely, malaria and irrigation; epidemic meningitis and land degradation; onchocerciasis and deforestation. We highlight the confounding effect of climate variability, which acts as a driver of both land-use change and human health. We conclude, as have others, that the scale of observation always matters, and complex and dynamic feedbacks among social-ecological systems are not easily teased apart. We suggest that in order to establish the causal chain of interactions between land-use change and human health outcomes two approaches are necessary. The first is to have a thorough understanding of the aetiology of disease and the specific mechanisms by which land-use and climate variability affect the transmission of pathogens. This is achieved by focused, detailed studies encompassing a wide range of potential drivers, which are inevitably small scale and often cover short time periods. The second consists of large-scale studies of statistical associations between transmission indices or health outcomes and environmental variables stratified by known ecological or socio-economic confounders, and sufficient in size to overcome local biases in results. Such research activities need to be designed to inform each other if we are to develop predictive models for monitoring these diseases and to develop integrated programs for human health and sustainable land use.

Watching television for more than two hours increases the likelihood of reporting poor sleep quality among Brazilian schoolteachers.

PubMed

de Souza, Sara Carolina Scremin; Campanini, Marcela Zambrim; de Andrade, Selma Maffei; González, Alberto Durán; de Melo, Juliana Moura; Mesas, Arthur Eumann

2017-10-01

Although time spent watching television and sleep problems have increased in the last few decades, it is unclear whether these conditions are associated in working adults after controlling for lifestyle, job characteristics and other individual aspects. The present study analyzed the association between time spent watching television and sleep quality among teachers from public schools in Londrina, Brazil. In this cross-sectional study, information from the Pittsburgh Sleep Quality Index (PSQI) and about time spent watching television was obtained during personal interviews. Logistic regression models adjusted by the main confounders (sociodemographic, occupational and lifestyle variables) were used in the analyses. Among the 959 studied teachers (68.2% women, median age: 42years), teachers who watched >120min/day had a higher likelihood of reporting poor sleep quality (PSQI>5) (odds ratio=1.41; 95% confidence interval=1.01; 1.98) compared with those who watched television for up to 60min/day, regardless of gender, age, work hours, leisure time physical activity and other lifestyle variables. This association did not remain significant after the adjustment for health conditions, i.e., obesity, anxiety, depression and chronic pain, which may act as confounding variables in the relationship between watching television and poor sleep quality. Watching television for >120min/day was independently associated with poorer sleep quality, which should be considered in the prevention and treatment of sleep disturbances among working population. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain tumors in children and occupational exposure of parents.

PubMed

Peters, F M; Preston-Martin, S; Yu, M C

1981-07-10

Ninety-two cases of brain tumor in children less than 10 years old were compared with 92 matched controls for parental occupational history. Cases were more likely than controls to show material occupations involving chemical exposure, paternal occupations involving solvents, and employment of father in the aircraft industry. These three factors were not affected by adjustment for the potential confounding variables examined in this study.

Thyroid disorders in older adults.

PubMed

Visser, W Edward; Visser, Theo J; Peeters, Robin P

2013-06-01

This article summarizes the current literature about serum thyroid parameters and thyroid disease during aging. Changes in thyroid function tests may be part of the physiology of aging, after exclusion of confounding variables. Overt thyroid disease requires immediate treatment. Treatment of subclinical hyperthyroidism in the elderly can be advocated, while watchful waiting may be an appropriate approach for subclinical hypothyroidism. Copyright © 2013 Elsevier Inc. All rights reserved.

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…

An Assessment of the Influence of Attention to the Task in the Measurement of Visual Perceptual Abilities. Final Report.

ERIC Educational Resources Information Center

Rodenborn, Leo V., Jr.

The project's purpose was to determine whether attention to the task during testing was a confounding variable in measures of visual perception ability. Samples of 30 perceptually handicapped (PH) and 30 normal subjects (N) were randomly selected from children so classified on the Frostig DTVP, providing they had IQ scores between 85 and 115 on…

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.

Reducing the Language Content in ToM Tests: A Developmental Scale

ERIC Educational Resources Information Center

Burnel, Morgane; Perrone-Bertolotti, Marcela; Reboul, Anne; Baciu, Monica; Durrleman, Stephanie

2018-01-01

The goal of the current study was to statistically evaluate the reliable scalability of a set of tasks designed to assess Theory of Mind (ToM) without language as a confounding variable. This tool might be useful to study ToM in populations where language is impaired or to study links between language and ToM. Low verbal versions of the ToM tasks…

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.

Impact of singlehood during pregnancy on dietary intake and birth outcomes- a study in the Norwegian Mother and Child Cohort Study.

PubMed

Farbu, Jorunn; Haugen, Margaretha; Meltzer, Helle Margrete; Brantsæter, Anne Lise

2014-12-05

Little attention has been given to the impact of singlehood during pregnancy. The aim of this study was to examine the impact of marital status on diet during pregnancy and pregnancy outcome. The study population comprised 62,773 women participating in the Norwegian Mother and Child Cohort Study. Marital status was categorised into singles living alone, singles living with parents and married/cohabiting (reference group). Participants answered a general health questionnaire in gestational week 15-17 and a food frequency questionnaire in gestational week 22. We used nonparametric tests to compare dietary intakes by marital status, and multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for infants being small for gestational age (SGA), large for gestational age (LGA), and preterm delivery (defined as delivery before gestational week 37). Single women living with parents had lower intakes of fruits and vegetables, higher intake of total energy, higher proportion of energy from added sugar, and lower intake of fibre than the reference group. Singles living alone also had a higher intake of added sugar. In both of the single groups, daily smoking was more prevalent than in women living with a partner. In analyses adjusted for maternal age, pre-pregnancy BMI, energy intake, energy contributed by protein, education, income, parity and nausea, single women living alone had increased risk of SGA with OR = 1.27 (95% CI: 1.05, 1.55). When smoking was included among the confounding variables, the association was no longer significant. Likewise, singles living alone had increased risk of preterm delivery, with OR = 1.32 (95% CI: 1.01, 1.72) in a partly adjusted model, but the association did not remain significant in a model fully adjusted for confounding variables. Single mothers had lower dietary quality and included more smokers than women who lived with a partner. Single mothers living alone had higher prevalence of SGA and preterm delivery, but the associations with adverse pregnancy outcomes were confounded by other variables. This study shows that single mothers should be given special attention during antenatal care and counselling.

Response variables for evaluation of the effectiveness of conservation corridors.

PubMed

Gregory, Andrew J; Beier, Paul

2014-06-01

Many studies have evaluated effectiveness of corridors by measuring species presence in and movement through small structural corridors. However, few studies have assessed whether these response variables are adequate for assessing whether the conservation goals of the corridors have been achieved or considered the costs or lag times involved in measuring the response variables. We examined 4 response variables-presence of the focal species in the corridor, interpatch movement via the corridor, gene flow, and patch occupancy--with respect to 3 criteria--relevance to conservation goals, lag time (fewest generations at which a positive response to the corridor might be evident with a particular variable), and the cost of a study when applying a particular variable. The presence variable had the least relevance to conservation goals, no lag time advantage compared with interpatch movement, and only a moderate cost advantage over interpatch movement or gene flow. Movement of individual animals between patches was the most appropriate response variable for a corridor intended to provide seasonal migration, but it was not an appropriate response variable for corridor dwellers, and for passage species it was only moderately relevant to the goals of gene flow, demographic rescue, and recolonization. Response variables related to gene flow provided a good trade-off among cost, relevance to conservation goals, and lag time. Nonetheless, the lag time of 10-20 generations means that evaluation of conservation corridors cannot occur until a few decades after a corridor has been established. Response variables related to occupancy were most relevant to conservation goals, but the lag time and costs to detect corridor effects on occupancy were much greater than the lag time and costs to detect corridor effects on gene flow. © 2014 Society for Conservation Biology.

Relation between sick leave and selected exposure variables among women semiconductor workers in Malaysia

PubMed Central

Chee, H; Rampal, K

2003-01-01

Aims: To determine the relation between sick leave and selected exposure variables among women semiconductor workers. Methods: This was a cross sectional survey of production workers from 18 semiconductor factories. Those selected had to be women, direct production operators up to the level of line leader, and Malaysian citizens. Sick leave and exposure to physical and chemical hazards were determined by self reporting. Three sick leave variables were used; number of sick leave days taken in the past year was the variable of interest in logistic regression models where the effects of age, marital status, work task, work schedule, work section, and duration of work in factory and work section were also explored. Results: Marital status was strongly linked to the taking of sick leave. Age, work schedule, and duration of work in the factory were significant confounders only in certain cases. After adjusting for these confounders, chemical and physical exposures, with the exception of poor ventilation and smelling chemicals, showed no significant relation to the taking of sick leave within the past year. Work section was a good predictor for taking sick leave, as wafer polishing workers faced higher odds of taking sick leave for each of the three cut off points of seven days, three days, and not at all, while parts assembly workers also faced significantly higher odds of taking sick leave. Conclusion: In Malaysia, the wafer fabrication factories only carry out a limited portion of the work processes, in particular, wafer polishing and the processes immediately prior to and following it. This study, in showing higher illness rates for workers in wafer polishing compared to semiconductor assembly, has implications for the governmental policy of encouraging the setting up of wafer fabrication plants with the full range of work processes. PMID:12660374

Temperature Variability during Delirium in ICU Patients: An Observational Study

PubMed Central

van der Kooi, Arendina W.; Kappen, Teus H.; Raijmakers, Rosa J.; Zaal, Irene J.; Slooter, Arjen J. C.

2013-01-01

Introduction Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and –nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. Methods We included patients who experienced both delirium and delirium free days during ICU stay, based on the Confusion Assessment method for the ICU conducted by a research- physician or –nurse, in combination with inspection of medical records. We excluded patients with conditions affecting thermal regulation or therapies affecting body temperature. Daily temperature variability was determined by computing the mean absolute second derivative of the temperature signal. Temperature variability (primary outcome) and absolute body temperature (secondary outcome) were compared between delirium- and non-delirium days with a linear mixed model and adjusted for daily mean Richmond Agitation and Sedation Scale scores and daily maximum Sequential Organ Failure Assessment scores. Results Temperature variability was increased during delirium-days compared to days without delirium (βunadjusted=0.007, 95% confidence interval (CI)=0.004 to 0.011, p<0.001). Adjustment for confounders did not alter this result (βadjusted=0.005, 95% CI=0.002 to 0.008, p<0.001). Delirium was not associated with absolute body temperature (βunadjusted=-0.03, 95% CI=-0.17 to 0.10, p=0.61). This did not change after adjusting for confounders (βadjusted=-0.03, 95% CI=-0.17 to 0.10, p=0.63). Conclusions Our study suggests that temperature variability is increased during ICU delirium. PMID:24194955

Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review.

PubMed

Luijendijk, Hendrika J; de Bruin, Niels C; Hulshof, Tessa A; Koolman, Xander

2016-02-01

Numerous large observational studies have shown an increased risk of mortality in elderly users of conventional antipsychotics. Health authorities have warned against use of these drugs. However, terminal illness is a potentially strong confounder of the observational findings. So, the objective of this study was to systematically assess whether terminal illness may have biased the observational association between conventional antipsychotics and risk of mortality in elderly patients. Studies were searched in PubMed, CINAHL, Embase, the references of selected studies and articles referring to selected studies (Web of Science). Inclusion criteria were (i) observational studies that estimated (ii) the risk of all-cause mortality in (iii) new elderly users of (iv) conventional antipsychotics compared with atypical antipsychotics or no use. Two investigators assessed the characteristics of the exposure and reference groups, main results, measured confounders and methods used to adjust for unmeasured confounders. We identified 21 studies. All studies were based on administrative medical and pharmaceutical databases. Sicker and older patients received conventional antipsychotics more often than new antipsychotics. The risk of dying was especially high in the first month of use, and when haloperidol was administered per injection or in high doses. Terminal illness was not measured in any study. Instrumental variables that were used were also confounded by terminal illness. We conclude that terminal illness has not been adjusted for in observational studies that reported an increased risk of mortality risk in elderly users of conventional antipsychotics. As the validity of the evidence is questionable, so is the warning based on it. Copyright © 2015 John Wiley & Sons, Ltd.

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.

LC-MS Analysis of Human Platelets as a Platform for Studying Mitochondrial Metabolism

PubMed Central

Parry, Robert C.; Wang, Qingqing; Gillespie, Kevin P.; Saillant, Noelle N.; Sims, Carrie; Mesaros, Clementina; Snyder, Nathaniel W.; Blair, Ian A.

2016-01-01

Perturbed mitochondrial metabolism has received renewed interest as playing a causative role in a range of diseases. Probing alterations to metabolic pathways requires a model in which external factors can be well controlled, allowing for reproducible and meaningful results. Many studies employ transformed cellular models for these purposes; however, metabolic reprogramming that occurs in many cancer cell lines may introduce confounding variables. For this reason primary cells are desirable, though attaining adequate biomass for metabolic studies can be challenging. Here we show that human platelets can be utilized as a platform to carry out metabolic studies in combination with liquid chromatography-tandem mass spectrometry analysis. This approach is amenable to relative quantification and isotopic labeling to probe the activity of specific metabolic pathways. Availability of platelets from individual donors or from blood banks makes this model system applicable to clinical studies and feasible to scale up. Here we utilize isolated platelets to confirm previously identified compensatory metabolic shifts in response to the complex I inhibitor rotenone. More specifically, a decrease in glycolysis is accompanied by an increase in fatty acid oxidation to maintain acetyl-CoA levels. Our results show that platelets can be used as an easily accessible and medically relevant model to probe the effects of xenobiotics on cellular metabolism. PMID:27077278

Relevance of Variations in the Opposing Dentition for the Functionality of Fixed and Removable Partial Dentures: A Systematic Review

PubMed Central

Pommer, Bernhard; Krainhöfner, Martin; Watzek, Georg; Tepper, Gabor; Dintsios, Charalabos-Markos

2012-01-01

The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a “biometric quality” tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a) the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b) the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture. PMID:23193407

Improving gridded snow water equivalent products in British Columbia, Canada: multi-source data fusion by neural network models

NASA Astrophysics Data System (ADS)

Snauffer, Andrew M.; Hsieh, William W.; Cannon, Alex J.; Schnorbus, Markus A.

2018-03-01

Estimates of surface snow water equivalent (SWE) in mixed alpine environments with seasonal melts are particularly difficult in areas of high vegetation density, topographic relief, and snow accumulations. These three confounding factors dominate much of the province of British Columbia (BC), Canada. An artificial neural network (ANN) was created using as predictors six gridded SWE products previously evaluated for BC. Relevant spatiotemporal covariates were also included as predictors, and observations from manual snow surveys at stations located throughout BC were used as target data. Mean absolute errors (MAEs) and interannual correlations for April surveys were found using cross-validation. The ANN using the three best-performing SWE products (ANN3) had the lowest mean station MAE across the province. ANN3 outperformed each product as well as product means and multiple linear regression (MLR) models in all of BC's five physiographic regions except for the BC Plains. Subsequent comparisons with predictions generated by the Variable Infiltration Capacity (VIC) hydrologic model found ANN3 to better estimate SWE over the VIC domain and within most regions. The superior performance of ANN3 over the individual products, product means, MLR, and VIC was found to be statistically significant across the province.

Use of Causal Diagrams to Inform the Design and Interpretation of Observational Studies: An Example from the Study of Heart and Renal Protection (SHARP).

PubMed

Staplin, Natalie; Herrington, William G; Judge, Parminder K; Reith, Christina A; Haynes, Richard; Landray, Martin J; Baigent, Colin; Emberson, Jonathan

2017-03-07

Observational studies often seek to estimate the causal relevance of an exposure to an outcome of interest. However, many possible biases can arise when estimating such relationships, in particular bias because of confounding. To control for confounding properly, careful consideration of the nature of the assumed relationships between the exposure, the outcome, and other characteristics is required. Causal diagrams provide a simple graphic means of displaying such relationships, describing the assumptions made, and allowing for the identification of a set of characteristics that should be taken into account ( i.e. , adjusted for) in any analysis. Furthermore, causal diagrams can be used to identify other possible sources of bias (such as selection bias), which if understood from the outset, can inform the planning of appropriate analyses. In this article, we review the basic theory of causal diagrams and describe some of the methods available to identify which characteristics need to be taken into account when estimating the total effect of an exposure on an outcome. In doing so, we review the concept of collider bias and show how it is inappropriate to adjust for characteristics that may be influenced, directly or indirectly, by both the exposure and the outcome of interest. A motivating example is taken from the Study of Heart and Renal Protection, in which the relevance of smoking to progression to ESRD is considered. Copyright © 2017 by the American Society of Nephrology.

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.

Striatal action-value neurons reconsidered.

PubMed

Elber-Dorozko, Lotem; Loewenstein, Yonatan

2018-05-31

It is generally believed that during economic decisions, striatal neurons represent the values associated with different actions. This hypothesis is based on studies, in which the activity of striatal neurons was measured while the subject was learning to prefer the more rewarding action. Here we show that these publications are subject to at least one of two critical confounds. First, we show that even weak temporal correlations in the neuronal data may result in an erroneous identification of action-value representations. Second, we show that experiments and analyses designed to dissociate action-value representation from the representation of other decision variables cannot do so. We suggest solutions to identifying action-value representation that are not subject to these confounds. Applying one solution to previously identified action-value neurons in the basal ganglia we fail to detect action-value representations. We conclude that the claim that striatal neurons encode action-values must await new experiments and analyses. © 2018, Elber-Dorozko et al.

Residential proximity to industrial sites in the area of Taranto (Southern Italy). A case-control cancer incidence study.

PubMed

Marinaccio, Alessandro; Belli, Stefano; Binazzi, Alessandra; Scarselli, Alberto; Massari, Stefania; Bruni, Antonella; Conversano, Michele; Crosignani, Paolo; Minerba, Aldo; Zona, Amerigo; Comba, Pietro

2011-01-01

The association between cancer incidence and the residence near polluting facilities in an industrial area nearby Taranto has been investigated. Age, sex and occupational exposure were controlled as confounding variables in a case-control study (658 cases, 2092 controls). High risks were evidenced close to the steel mill (OR: 3.54), coke plant (OR: 4.80), mineral deposit (OR: 3.33) and shipbuilding (OR: 4.29) for pleural neoplasm, and to the steel mill (OR: 1.65) and shipbuilding (OR: 1.79) for lung cancer. After adjustment for occupational exposure, increasing trends of risk were observed both for lung and bladder cancers. Cancer risks were evidenced near industrial sites and the introduction of "occupational exposure" as a confounder modified significantly the risks with respect to distance from the source of pollution, particularly for pleural, lung and bladder cancers.

Memory Test Performance on Analogous Verbal and Nonverbal Memory Tests in Patients with Frontotemporal Dementia and Alzheimer's Disease.

PubMed

Baldock, Deanna; Miller, Justin B; Leger, Gabriel C; Banks, Sarah Jane

2016-01-01

Patients with frontotemporal dementia (FTD) typically have initial deficits in language or changes in personality, while the defining characteristic of Alzheimer's disease (AD) is memory impairment. Neuropsychological findings in the two diseases tend to differ, but can be confounded by verbal impairment in FTD impacting performance on memory tests in these patients. Twenty-seven patients with FTD and 102 patients with AD underwent a neuropsychological assessment before diagnosis. By utilizing analogous versions of a verbal and nonverbal memory test, we demonstrated differences in these two modalities between AD and FTD. Better differentiation between AD and FTD is found in a nonverbal memory test, possibly because it eliminates the confounding variable of language deficits found in patients with FTD. These results highlight the importance of nonverbal learning tests with multiple learning trials in diagnostic testing.

Influence of management history and landscape variables on soil organic carbon and soil redistribution

USGS Publications Warehouse

Venteris, E.R.; McCarty, G.W.; Ritchie, J.C.; Gish, T.

2004-01-01

Controlled studies to investigate the interaction between crop growth, soil properties, hydrology, and management practices are common in agronomy. These sites (much as with real world farmland) often have complex management histories and topographic variability that must be considered. In 1993 an interdisiplinary study was started for a 20-ha site in Beltsville, MD. Soil cores (271) were collected in 1999 in a 30-m grid (with 5-m nesting) and analyzed as part of the site characterization. Soil organic carbon (SOC) and 137Cesium (137Cs) were measured. Analysis of aerial photography from 1992 and of farm management records revealed that part of the site had been maintained as a swine pasture and the other portion as cropped land. Soil properties, particularly soil redistribution and SOC, show large differences in mean values between the two areas. Mass C is 0.8 kg m -2 greater in the pasture area than in the cropped portion. The pasture area is primarily a deposition site, whereas the crop area is dominated by erosion. Management influence is suggested, but topographic variability confounds interpretation. Soil organic carbon is spatially structured, with a regionalized variable of 120 m. 137Cs activity lacks spatial structure, suggesting disturbance of the profile by animal activity and past structures such as swine shelters and roads. Neither SOC nor 137Cs were strongly correlated to terrain parameters, crop yields, or a seasonal soil moisture index predicted from crop yields. SOC and 137Cs were weakly correlated (r2 ???0.2, F-test P-value 0.001), suggesting that soil transport controls, in part, SOC distribution. The study illustrates the importance of past site history when interpreting the landscape distribution of soil properties, especially those strongly influenced by human activity. Confounding variables, complex soil hydrology, and incomplete documentation of land use history make definitive interpretations of the processes behind the spatial distributions difficult. Such complexity may limit the accuracy of scaling approaches to mapping SOC and soil redistribution.

Factors affecting urine reagent strip blood results in dogs and nonhuman primates and interpretation of urinalysis in preclinical toxicology studies: a Multi-Institution Contract Research Organization and BioPharmaceutical Company Perspective.

PubMed

Aulbach, Adam D; Schultze, Eric; Tripathi, Niraj K; Hall, Robert L; Logan, Michael R; Meyer, Denny J

2015-06-01

Urinalysis data in preclinical toxicology studies can be influenced by preanalytic and analytic factors which have the potential to confound interpretation. There is a paucity of information regarding positive reagent strip urinary blood reactions in healthy nonhuman primates (NHP) and Beagle dogs used in preclinical toxicology studies. The objectives were (1) to establish historical control data for reagent strip urinary blood reactions in healthy NHP and Beagle dogs, (2) to determine the incidence of positive urinary blood reactions during predose and dosing phases, and (3) to determine if collection practice was a relevant parameter. Historical control data from 2 institutions in the biopharmaceutical industry were retrospectively analyzed for reagent strip urinary blood reactions in healthy NHP and Beagles. The incidence of positive results between the 2 institutions with different urine collection practices and between males and females was compared. The incidence of positive urinary blood reactions in NHP was comparable between institutions (≤ 14% in males; ≤ 33% in females), while the incidence of positive urinary blood reactions in Beagles was more variable (≤ 77% in males; ≤ 69% in females), and higher in females during the dosing phase. Positive urinary blood results that could potentially be misinterpreted as toxicologically relevant were identified in healthy NHP and Beagles during predose and dosing phases. Different incidences of positive results between the 2 institutions were likely related to collection practices. Strategies to reduce feces and food contamination of collected urine samples should help minimize false-positive urinary blood reactions. © 2015 American Society for Veterinary Clinical Pathology.

Factorial Structure and Preliminary Validation of the Schema Mode Inventory for Eating Disorders (SMI-ED)

PubMed Central

Simpson, Susan G.; Pietrabissa, Giada; Rossi, Alessandro; Seychell, Tahnee; Manzoni, Gian Mauro; Munro, Calum; Nesci, Julian B.; Castelnuovo, Gianluca

2018-01-01

Objective: The aim of this study was to examine the psychometric properties and factorial structure of the Schema Mode Inventory for Eating Disorders (SMI-ED) in a disordered eating population. Method: 573 participants with disordered eating patterns as measured by the Eating Disorder Examination Questionnaire (EDE-Q) completed the 190-item adapted version of the Schema Mode Inventory (SMI). The new SMI-ED was developed by clinicians/researchers specializing in the treatment of eating disorders, through combining items from the original SMI with a set of additional questions specifically representative of the eating disorder population. Psychometric testing included Confirmatory Factor Analysis (CFA) and internal consistency (Cronbach's α). Multivariate Analyses of Covariance (MANCOVA) was also run to test statistical differences between the EDE-Q subscales on the SMI-ED modes, while controlling for possible confounding variables. Results: Factorial analysis confirmed an acceptable 16-related-factors solution for the SMI-ED, thus providing preliminary evidence for the adequate validity of the new measure based on internal structure. Concurrent validity was also established through moderate to high correlations on the modes most relevant to eating disorders with EDE-Q subscales. This study represents the first step in creating a psychometrically sound instrument for measuring schema modes in eating disorders, and provides greater insight into the relevant schema modes within this population. Conclusion: This research represents an important preliminary step toward understanding and labeling the schema mode model for this clinical group. Findings from the psychometric evaluation of SMI-ED suggest that this is a useful tool which may further assist in the measurement and conceptualization of schema modes in this population. PMID:29740379

Factorial Structure and Preliminary Validation of the Schema Mode Inventory for Eating Disorders (SMI-ED).

PubMed

Simpson, Susan G; Pietrabissa, Giada; Rossi, Alessandro; Seychell, Tahnee; Manzoni, Gian Mauro; Munro, Calum; Nesci, Julian B; Castelnuovo, Gianluca

2018-01-01

Objective: The aim of this study was to examine the psychometric properties and factorial structure of the Schema Mode Inventory for Eating Disorders (SMI-ED) in a disordered eating population. Method: 573 participants with disordered eating patterns as measured by the Eating Disorder Examination Questionnaire (EDE-Q) completed the 190-item adapted version of the Schema Mode Inventory (SMI). The new SMI-ED was developed by clinicians/researchers specializing in the treatment of eating disorders, through combining items from the original SMI with a set of additional questions specifically representative of the eating disorder population. Psychometric testing included Confirmatory Factor Analysis (CFA) and internal consistency (Cronbach's α). Multivariate Analyses of Covariance (MANCOVA) was also run to test statistical differences between the EDE-Q subscales on the SMI-ED modes, while controlling for possible confounding variables. Results: Factorial analysis confirmed an acceptable 16-related-factors solution for the SMI-ED, thus providing preliminary evidence for the adequate validity of the new measure based on internal structure. Concurrent validity was also established through moderate to high correlations on the modes most relevant to eating disorders with EDE-Q subscales. This study represents the first step in creating a psychometrically sound instrument for measuring schema modes in eating disorders, and provides greater insight into the relevant schema modes within this population. Conclusion: This research represents an important preliminary step toward understanding and labeling the schema mode model for this clinical group. Findings from the psychometric evaluation of SMI-ED suggest that this is a useful tool which may further assist in the measurement and conceptualization of schema modes in this population.

Associations between renaming schizophrenia and stigma-related outcomes: A systematic review.

PubMed

Yamaguchi, Sosei; Mizuno, Masashi; Ojio, Yasutaka; Sawada, Utako; Matsunaga, Asami; Ando, Shuntaro; Koike, Shinsuke

2017-06-01

Renaming schizophrenia is a potential strategy to reduce the stigma attached to people with schizophrenia. However, the overall associations between renaming schizophrenia and stigma-related outcomes have not been fully elucidated. We conducted a systematic review of studies that empirically examined the outcomes between new or alternative terms and old or existing terms for schizophrenia. We searched for relevant articles in eight bibliographic databases, conducted a Google search, examined reference lists, and contacted relevant experts. We found a total of 2601 reference records, and 23 articles were included in this review. Overall, in countries where schizophrenia has been renamed, the name changes may be associated with improvements in adults' attitudes toward people with schizophrenia, and with increased diagnosis announcement. However, studies conducted in countries where schizophrenia has not been renamed report inconsistent findings. In addition, renaming may not influence portrayals of schizophrenia in the media. Most studies included in our review had a risk of bias in their methodology, and we employed a vote-counting method to synthesize study results; therefore, the impacts of renaming are still inconclusive. Future studies are needed to address the following issues: use of univariate descriptive statistics, adjustment for confounding variables, use of reliable measures, and employing a question that addresses the image of split or multiple personalities. Evidence is limited regarding the associations between renaming and stigma experienced by both people with schizophrenia and their families (e.g., perceived stigma, self-stigma, discrimination experience, and burden). Further research in these populations is needed to confirm the effects of renaming schizophrenia. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Selection of higher order regression models in the analysis of multi-factorial transcription data.

PubMed

Prazeres da Costa, Olivia; Hoffman, Arthur; Rey, Johannes W; Mansmann, Ulrich; Buch, Thorsten; Tresch, Achim

2014-01-01

Many studies examine gene expression data that has been obtained under the influence of multiple factors, such as genetic background, environmental conditions, or exposure to diseases. The interplay of multiple factors may lead to effect modification and confounding. Higher order linear regression models can account for these effects. We present a new methodology for linear model selection and apply it to microarray data of bone marrow-derived macrophages. This experiment investigates the influence of three variable factors: the genetic background of the mice from which the macrophages were obtained, Yersinia enterocolitica infection (two strains, and a mock control), and treatment/non-treatment with interferon-γ. We set up four different linear regression models in a hierarchical order. We introduce the eruption plot as a new practical tool for model selection complementary to global testing. It visually compares the size and significance of effect estimates between two nested models. Using this methodology we were able to select the most appropriate model by keeping only relevant factors showing additional explanatory power. Application to experimental data allowed us to qualify the interaction of factors as either neutral (no interaction), alleviating (co-occurring effects are weaker than expected from the single effects), or aggravating (stronger than expected). We find a biologically meaningful gene cluster of putative C2TA target genes that appear to be co-regulated with MHC class II genes. We introduced the eruption plot as a tool for visual model comparison to identify relevant higher order interactions in the analysis of expression data obtained under the influence of multiple factors. We conclude that model selection in higher order linear regression models should generally be performed for the analysis of multi-factorial microarray data.

Gender differences in illness behavior after cardiac surgery.

PubMed

Modica, Maddalena; Ferratini, Maurizio; Spezzaferri, Rosa; De Maria, Renata; Previtali, Emanuele; Castiglioni, Paolo

2014-01-01

Differences in the ways male and female patients confront their illness after cardiac surgery may contribute to previously observed gender differences in the outcomes of cardiac rehabilitation. The aim of this cross-sectional study was to verify whether there are gender-related differences in illness behavior (IB) soon after cardiac surgery and before entering cardiac rehabilitation. Patients (N = 1323) completed the IB Questionnaire and Hospital Anxiety and Depression Scale (HADS) 9 ± 5 (mean ± SD) days after cardiac surgery. The scores were tested for gender differences in score distributions (Mann-Whitney U test) and in prevalence of clinically relevant scores (the Pearson χ² test). Multivariate regression analyses were made with IB Questionnaire and HADS scores as independent variables, and gender, age, education, marital status, and type of surgery as predictors. Denial was significantly (P < .01) prevalent among the men (3.6 ± 1.4) versus women (3.2 ± 1.6), whereas disease conviction (men = 2.1 ± 1.5, women = 2.5 ± 1.6), dysphoria (men = 1.5 ± 1.5, women = 2.0 ± 1.6), anxiety (men = 6.0 ± 3.6, women = 6.9 ± 3.9), and depression (men = 5.3 ± 3.8, women = 6.5 ± 4.0) were significantly more prevalent among women. The prevalences of clinically relevant scores for disease conviction, anxiety, and depression were also significantly higher in women. Multivariate analysis showed that gender predicted these scores even after the removal of confounders. Gender differences exist in denial, disease conviction, and dysphoria, probably depending on the culturally assigned roles of men and women. As these aspects of IB may compromise treatment compliance and the quality of life, the efficacy of cardiac rehabilitation programs might be improved taking into account the different prevalences in men and women.

Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

PubMed Central

Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

2014-01-01

A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

Acute alcohol consumption, alcohol outlets, and gun suicide.

PubMed

Branas, Charles C; Richmond, Therese S; Ten Have, Thomas R; Wiebe, Douglas J

2011-01-01

A case-control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed.

Exploratory reconstructability analysis of accident TBI data

NASA Astrophysics Data System (ADS)

Zwick, Martin; Carney, Nancy; Nettleton, Rosemary

2018-02-01

This paper describes the use of reconstructability analysis to perform a secondary study of traumatic brain injury data from automobile accidents. Neutral searches were done and their results displayed with a hypergraph. Directed searches, using both variable-based and state-based models, were applied to predict performance on two cognitive tests and one neurological test. Very simple state-based models gave large uncertainty reductions for all three DVs and sizeable improvements in percent correct for the two cognitive test DVs which were equally sampled. Conditional probability distributions for these models are easily visualized with simple decision trees. Confounding variables and counter-intuitive findings are also reported.

Fish Oil Supplementation and Fatty Acid Synthase Expression in the Prostate: A Randomized Controlled Trial

DTIC Science & Technology

2010-03-20

olive oil (placebo) capsules (treatment 2). Potential confounding variables are assessed through completion of a comprehensive diet history...AD_________________ Award Number: W81XWH-04-1-0296 TITLE: Fish Oil Supplementation and Fatty Acid...FORM TO THE ABOVE ADDRESS. 31-03-2010 1. REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 0 3. DATES COVERED (From - To) Fish Oil Supplementation and

Equal Pay for Equal Work in Academic Obstetrics and Gynecology.

PubMed

Eichelberger, Kacey Y

2018-02-01

The most compelling data suggest women in academic obstetrics and gynecology earn approximately $36,000 less than male colleagues per year in regression models correcting for commonly cited explanatory variables. Although residual confounding may exist, academic departments in the United States should consider rigorous examination of their own internal metrics around salary to ensure gender-neutral compensation, commonly referred to as equal pay for equal work.

Errors in causal inference: an organizational schema for systematic error and random error.

PubMed

Suzuki, Etsuji; Tsuda, Toshihide; Mitsuhashi, Toshiharu; Mansournia, Mohammad Ali; Yamamoto, Eiji

2016-11-01

To provide an organizational schema for systematic error and random error in estimating causal measures, aimed at clarifying the concept of errors from the perspective of causal inference. We propose to divide systematic error into structural error and analytic error. With regard to random error, our schema shows its four major sources: nondeterministic counterfactuals, sampling variability, a mechanism that generates exposure events and measurement variability. Structural error is defined from the perspective of counterfactual reasoning and divided into nonexchangeability bias (which comprises confounding bias and selection bias) and measurement bias. Directed acyclic graphs are useful to illustrate this kind of error. Nonexchangeability bias implies a lack of "exchangeability" between the selected exposed and unexposed groups. A lack of exchangeability is not a primary concern of measurement bias, justifying its separation from confounding bias and selection bias. Many forms of analytic errors result from the small-sample properties of the estimator used and vanish asymptotically. Analytic error also results from wrong (misspecified) statistical models and inappropriate statistical methods. Our organizational schema is helpful for understanding the relationship between systematic error and random error from a previously less investigated aspect, enabling us to better understand the relationship between accuracy, validity, and precision. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Breastfeeding on Head Circumference of Children from Impoverished Communities

PubMed Central

Xavier Júnior, Antonio Fernando Silva; de Assunção, Monica Lopes; dos Santos, Ewerton Amorim; Horta, Bernardo Lessa

2013-01-01

Abstract Objective This study investigated the effect of exclusive breastfeeding on head circumference (HC) among children living in impoverished communities. Subjects and Methods A cross-sectional study was conducted among children 12–60 months old from the 39 quilombos located in the State of Alagoas, Brazil. HC deficit was defined by a z-score of less than −2 from the median (based on the 2006 World Health Organization growth standards). Prevalence ratio and 95% confidence interval (95% CI) were estimated using Poisson regression with robust adjustment of the variance, and estimates were adjusted for possible confounders (anthropometric, socioeconomic, demographic, and health-related variables). Results We evaluated 725 children (365 boys and 360 girls). The prevalence of HC deficit was 13.3% among those children who were exclusively breastfed for less than 30 days, 10.6% among those exclusively breastfed for 30–119 days, and 5.8% among those who were exclusively breastfed for 120 days or more. Even after controlling for possible confounding variables, exclusive breastfeeding for ≥4 months decreased the risk of HC deficit (prevalence ratio, 0.48; 95% CI 0.24, 0.99). Conclusions Exclusive breastfeeding for ≥4 months was associated with a larger HC in children exposed to great social vulnerability in impoverished communities. PMID:23414229

Association between indoor and outdoor air pollution and adolescent asthma from 1995 to 1996 in Taiwan

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

Wang, T.N.; Ko, Y.C.; Chao, Y.Y.

The study aim was to estimate the contribution of indoor and outdoor air pollution to the 1-year prevalence of adolescent asthma after personal susceptibility and other potential risk factors were taken into account. A large-scaled cross-sectional study was conducted among 165,173 high school students aged 11 to 16 years in the different communities of Kaohsiung and Pintong in Taiwan, from October 1995 to June 1996. Each student and his/her parents participating in the study completed a video and a written International Study of Asthma and Allergies in Childhood questionnaire about symptoms of wheezing and allergies, passive smoking, and demographic variables.more » After adjustment for potential confounders, adolescents exposed to cigarette smoking and environmental tobacco smoke were found to suffer from asthma at an increased frequency. The authors observed a statistically significant association between outdoor air pollution and asthma, after controlling for potential confound variables. Total suspended particulate, nitrogen dioxide, carbon monoxide, ozone, and airborne dust particles all displayed an independent association with asthma, respectively. There were no selection biases in this community-based study, which provides evidence that passive smoking and long-term, high average outdoor air pollution are independent risk factors of asthma.« less

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.

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.

Goal specificity: a proxy measure for improvements in environmental outcomes in collaborative governance.

PubMed

Biddle, Jennifer C; Koontz, Tomas M

2014-12-01

Collaborative governance critics continually call for evidence to support its prevalent use. As is often the case in environmental policy, environmental outcomes occur at a rate incompatible with political agendas. In addition, a multitude of possibly confounding variables makes it difficult to correlate collaborative governance processes with environmental outcomes. The findings of this study offer empirical evidence that collaborative processes have a measurable, beneficial effect on environmental outcomes. Through the use of a unique paired-waterbody design, our dataset reduced the potential for confounding variables to impact our environmental outcome measurements. The results of a path analysis indicate that the output of setting specific pollutant reduction goals is significantly related to watershed partnerships' level of attainment of their environmental improvement goals. The action of setting specific goals (e.g. percentage of load reductions in pollutant levels) is fostered by sustained participation from partnership members throughout the lifecycle of the collaborative. In addition, this study demonstrates the utility of logic modeling for environmental planning and management, and suggests that the process of setting specific pollutant reduction goals is a useful proxy measure for reporting progress towards improvements in environmental outcomes when long-term environmental data are not available. Copyright © 2014 Elsevier Ltd. All rights reserved.

Napping during the night shift and recovery after work among hospital nurses1

PubMed Central

Palermo, Thaís Aparecida de Castro; Rotenberg, Lúcia; Zeitoune, Regina Célia Gollner; Silva-Costa, Aline; Souto, Ester Paiva; Griep, Rosane Härter

2015-01-01

OBJECTIVE: To analyze the association between the length of napping during the night shift and the recovery after work among nurses. METHOD: Cross-sectional epidemiological study involving 1940 nurses from 18 public hospitals in the City of Rio de Janeiro. A multidimensional and self-applied questionnaire was used with information about health, sociodemographic and occupational characteristics, health-related behaviors and housework. Multiple logistic regression was applied to identify the association, adjusted for confounding variables. RESULTS: The gross analyses showed 44%, 127% and 66% higher chances of a high level of recovery after work for nurses who sleep up to two hours, between 2.1 and 3 hours and 3.1 hours or more, respectively, when compared to the nurses who do not sleep. After adjusting for confounding variables, the association only continues significant for the group that sleeps 2.1 to 3 hours during the night shift (OR=1.79; 95%CI=1.33-2.41). CONCLUSION: The association between the length of napping and the high level of recovery after work, confirmed in the present results, can be included in the studies that aim to support more appropriate policies aimed at improving the workers' work, life and health conditions, not only in nursing, but night-shift workers in general. PMID:25806639

Measurement error is often neglected in medical literature: a systematic review.

PubMed

Brakenhoff, Timo B; Mitroiu, Marian; Keogh, Ruth H; Moons, Karel G M; Groenwold, Rolf H H; van Smeden, Maarten

2018-06-01

In medical research, covariates (e.g., exposure and confounder variables) are often measured with error. While it is well accepted that this introduces bias and imprecision in exposure-outcome relations, it is unclear to what extent such issues are currently considered in research practice. The objective was to study common practices regarding covariate measurement error via a systematic review of general medicine and epidemiology literature. Original research published in 2016 in 12 high impact journals was full-text searched for phrases relating to measurement error. Reporting of measurement error and methods to investigate or correct for it were quantified and characterized. Two hundred and forty-seven (44%) of the 565 original research publications reported on the presence of measurement error. 83% of these 247 did so with respect to the exposure and/or confounder variables. Only 18 publications (7% of 247) used methods to investigate or correct for measurement error. Consequently, it is difficult for readers to judge the robustness of presented results to the existence of measurement error in the majority of publications in high impact journals. Our systematic review highlights the need for increased awareness about the possible impact of covariate measurement error. Additionally, guidance on the use of measurement error correction methods is necessary. Copyright © 2018 Elsevier Inc. All rights reserved.

Viral Diseases in Zebrafish: What Is Known and Unknown

PubMed Central

Crim, Marcus J.; Riley, Lela K.

2013-01-01

Naturally occurring viral infections have the potential to introduce confounding variability that leads to invalid and misinterpreted data. Whereas the viral diseases of research rodents are well characterized and closely monitored, no naturally occurring viral infections have been characterized for the laboratory zebrafish (Danio rerio), an increasingly important biomedical research model. Despite the ignorance about naturally occurring zebrafish viruses, zebrafish models are rapidly expanding in areas of biomedical research where the confounding effects of unknown infectious agents present a serious concern. In addition, many zebrafish research colonies remain linked to the ornamental (pet) zebrafish trade, which can contribute to the introduction of new pathogens into research colonies, whereas mice used for research are purpose bred, with no introduction of new mice from the pet industry. Identification, characterization, and monitoring of naturally occurring viruses in zebrafish are crucial to the improvement of zebrafish health, the reduction of unwanted variability, and the continued development of the zebrafish as a model organism. This article addresses the importance of identifying and characterizing the viral diseases of zebrafish as the scope of zebrafish models expands into new research areas and also briefly addresses zebrafish susceptibility to experimental viral infection and the utility of the zebrafish as an infection and immunology model. PMID:23382345

Three estimates of the association between linear growth failure and cognitive ability.

PubMed

Cheung, Y B; Lam, K F

2009-09-01

To compare three estimators of association between growth stunting as measured by height-for-age Z-score and cognitive ability in children, and to examine the extent statistical adjustment for covariates is useful for removing confounding due to socio-economic status. Three estimators, namely random-effects, within- and between-cluster estimators, for panel data were used to estimate the association in a survey of 1105 pairs of siblings who were assessed for anthropometry and cognition. Furthermore, a 'combined' model was formulated to simultaneously provide the within- and between-cluster estimates. Random-effects and between-cluster estimators showed strong association between linear growth and cognitive ability, even after adjustment for a range of socio-economic variables. In contrast, the within-cluster estimator showed a much more modest association: For every increase of one Z-score in linear growth, cognitive ability increased by about 0.08 standard deviation (P < 0.001). The combined model verified that the between-cluster estimate was significantly larger than the within-cluster estimate (P = 0.004). Residual confounding by socio-economic situations may explain a substantial proportion of the observed association between linear growth and cognition in studies that attempt to control the confounding by means of multivariable regression analysis. The within-cluster estimator provides more convincing and modest results about the strength of association.

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.

Still too far to walk: literature review of the determinants of delivery service use.

PubMed

Gabrysch, Sabine; Campbell, Oona M R

2009-08-11

Skilled attendance at childbirth is crucial for decreasing maternal and neonatal mortality, yet many women in low- and middle-income countries deliver outside of health facilities, without skilled help. The main conceptual framework in this field implicitly looks at home births with complications. We expand this to include "preventive" facility delivery for uncomplicated childbirth, and review the kinds of determinants studied in the literature, their hypothesized mechanisms of action and the typical findings, as well as methodological difficulties encountered. We searched PubMed and Ovid databases for reviews and ascertained relevant articles from these and other sources. Twenty determinants identified were grouped under four themes: (1) sociocultural factors, (2) perceived benefit/need of skilled attendance, (3) economic accessibility and (4) physical accessibility. There is ample evidence that higher maternal age, education and household wealth and lower parity increase use, as does urban residence. Facility use in the previous delivery and antenatal care use are also highly predictive of health facility use for the index delivery, though this may be due to confounding by service availability and other factors. Obstetric complications also increase use but are rarely studied. Quality of care is judged to be essential in qualitative studies but is not easily measured in surveys, or without linking facility records with women. Distance to health facilities decreases use, but is also difficult to determine. Challenges in comparing results between studies include differences in methods, context-specificity and the substantial overlap between complex variables. Studies of the determinants of skilled attendance concentrate on sociocultural and economic accessibility variables and neglect variables of perceived benefit/need and physical accessibility. To draw valid conclusions, it is important to consider as many influential factors as possible in any analysis of delivery service use. The increasing availability of georeferenced data provides the opportunity to link health facility data with large-scale household data, enabling researchers to explore the influences of distance and service quality.

Appendicular and whole body lean mass outcomes are associated with finite element analysis-derived bone strength at the distal radius and tibia in adults aged 40years and older.

PubMed

Gibbs, Jenna C; Giangregorio, Lora M; Wong, Andy K O; Josse, Robert G; Cheung, Angela M

2017-10-01

The purpose of this cross-sectional study was to determine how appendicular lean mass index (ALMI), and whole body lean (LMI) and fat mass indices (FMI) associate with estimated bone strength outcomes at the distal radius and tibia in adults aged 40 years and older. Dual energy X-ray absorptiometry (DXA) scans were performed to determine body composition, including whole body lean and fat mass, and appendicular lean mass. ALMI (appendicular lean mass/height 2 ), LMI (lean tissue mass/height 2 ) and FMI (fat mass/height 2 ) were calculated. High-resolution peripheral quantitative computed tomography (HRpQCT) scans were performed to assess bone structural properties at the distal radius and tibia. Using finite element analysis, failure load (N), stiffness (N/mm), ultimate stress (MPa), and cortical-to-trabecular load ratio were estimated from HRpQCT scans. The associations between body composition (ALMI, LMI, FMI) and estimated bone strength were examined using bivariate and multivariable linear regression analyses adjusting for age, sex, and other confounding variables. In 197 participants (127 women; mean±SD, age: 69.5±10.3y, body mass index: 27.95±4.95kg/m 2 , ALMI: 7.31±1.31kg/m 2 ), ALMI and LMI were significantly associated with failure load at the distal radius and tibia (explained 39%-48% of the variance) and remained significant after adjusting for confounding variables and multiple testing (R 2 =0.586-0.645, p<0.001). ALMI, LMI, and FMI did not have significant associations with ultimate stress in our multivariable models. FMI was significantly associated with cortical-to-trabecular load ratio at the distal radius and tibia (explained 6%-12% of the variance) and remained significant after adjusting for confounders and multiple testing (R 2 =0.208-0.243, p<0.001). FMI was no longer significantly associated with failure load after adjusting for confounders. These findings suggest that ALMI and LMI are important determinants of estimated bone strength, particularly failure load, at the distal radius and tibia, and may contribute to preservation of bone strength in middle-to-late adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

Partial Granger causality--eliminating exogenous inputs and latent variables.

PubMed

Guo, Shuixia; Seth, Anil K; Kendrick, Keith M; Zhou, Cong; Feng, Jianfeng

2008-07-15

Attempts to identify causal interactions in multivariable biological time series (e.g., gene data, protein data, physiological data) can be undermined by the confounding influence of environmental (exogenous) inputs. Compounding this problem, we are commonly only able to record a subset of all related variables in a system. These recorded variables are likely to be influenced by unrecorded (latent) variables. To address this problem, we introduce a novel variant of a widely used statistical measure of causality--Granger causality--that is inspired by the definition of partial correlation. Our 'partial Granger causality' measure is extensively tested with toy models, both linear and nonlinear, and is applied to experimental data: in vivo multielectrode array (MEA) local field potentials (LFPs) recorded from the inferotemporal cortex of sheep. Our results demonstrate that partial Granger causality can reveal the underlying interactions among elements in a network in the presence of exogenous inputs and latent variables in many cases where the existing conditional Granger causality fails.

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

Attendance at cultural events, reading books or periodicals, and making music or singing in a choir as determinants for survival: Swedish interview survey of living conditions.

PubMed

Bygren, L O; Konlaan, B B; Johansson, S E

To investigate the possible influence of attendance at cultural events, reading books or periodicals, making music or singing in a choir as determinants for survival. A simple random sample was drawn of 15,198 individuals aged 16-74 years. Of these, 85% (12,982) were interviewed by trained non-medical interviewers between 1982 and 1983 about cultural activities. They were followed up with respect to survival until 31 December 1991. Swedish interview survey of living conditions comprising a random sample of the adult Swedish population. 12,675 people interviewed between 1982 and 1983. Survival of subjects after controlling for eight confounding variables: age, sex, education level, income, long term disease, social network, smoking, and physical exercise. 6,301 men and 6,374 women were followed up; 533 men and 314 women died during this period. The control variables influenced survival in the expected directions except for social network for men; a significant negative effective was found when the analysis was made separately for men and women. We found an influence on mortality when the eight control variables were controlled for in people who rarely attended events compared with those attending most often, the relative risk being 1.57 (95% confidence interval 1.18 to 2.09). Attendance at cultural events may have a positive influence on survival. Long term follow up of large samples with confounders that are well controlled for and with the cultural stimulation more highly specified should be used to try to falsify the hypothesis before experiments start.

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.

Perceived neighborhood environment and physical activity among high school students from Curitiba, Brazil.

PubMed

Lopes, Adalberto Aparecido dos Santos; Lanzoni, Alessandra Nunes; Hino, Adriano Akira Ferreira; Rodriguez-Añez, Ciro Romélio; Reis, Rodrigo Siqueira

2014-12-01

To analyze the association between perceived neighborhood environment and physical activity (PA) in high school students from Curitiba (PR), Brazil. A sample of 1,611 high school students from public schools was surveyed. The PA was assessed through questions, engaged for at least 20 minutes or 60 minutes. Perceptions on neighborhood environment were assessed through ten questions about neighborhood characteristics. Gender, age and number of cars in the household were self-reported and used as confounding variables. Absolute and relative frequencies were used in the sample, and associations were tested through adjusted logistic regressions for the confounding variables and stratified by gender (p < 0.05). The adjusted analyses showed that the variables "interesting things" among girls (OR = 1.77; 95%CI 1.05 - 2.96) and "there are places I like" (OR = 2.18; 95%CI 1.33 - 3.58) and "I see people my age", among boys, were associated with PA of at least 20 minutes/day once a week. Additionally, among boys, "I see people my age" was associated with 60-minute (OR = 1.68; 95%CI 1.15 - 2.45). Perceiving the neighborhood environment as "very good" was associated with higher chances of taking up PA among girls (OR = 1.92; 95%CI 1.15 - 3.22) and boys (OR = 3.13; 95%CI 1.97 - 4.97). A positive perception of the environment was associated to PA practice among boys and girls in this sample. The results suggest that some environmental characteristics which make neighborhoods more attractive could be related to PA among adolescents.

Functionally relevant climate variables for arid lands: Aclimatic water deficit approach for modelling desert shrub distributions

Treesearch

Thomas E. Dilts; Peter J. Weisberg; Camie M. Dencker; Jeanne C. Chambers

2015-01-01

We have three goals. (1) To develop a suite of functionally relevant climate variables for modelling vegetation distribution on arid and semi-arid landscapes of the Great Basin, USA. (2) To compare the predictive power of vegetation distribution models based on mechanistically proximate factors (water deficit variables) and factors that are more mechanistically removed...

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

PubMed

Mortimer, James A

2014-05-27

Editors' Note: Mortimer argues that important confounding variables may have biased the conclusion by Alladi et al. on the role of bilingualism in delaying the onset of dementia. Following Mortimer’s comments, Alladi et al. conducted additional analysis of their data to support their conclusion. The attitude of "close enough" is not appropriate when determining brain death. Stadlan comments and supports Frank’s call for action regarding this sensitive issue.

Understanding MIH: definition, epidemiology, differential diagnosis and new treatment guidelines.

PubMed

Mast, P; Rodrigueztapia, M T; Daeniker, L; Krejci, I

2013-09-01

Molar-Incisor Hypomineralisation (MIH) is a congenital disease which increases in prevalence. It affects permanent first molars and, often to a lesser degree, permanent incisors with variable severity. The aetiology is unknown, but different hypotheses have been advanced. Differential diagnosis is mandatory not to confound MIH with other diseases. Treatment consists in a minimally invasive approach by reinforcing and protecting the existing dental structure. In more severe cases, restorative treatment may be indicated.

Defense AT and L, Volume 41, Number 5, September - October 2012

DTIC Science & Technology

2012-09-01

subtle differences confound us. In the insurance industry, years, decades, and centuries of historical data give actuaries high confidence in making...live another 23.26 years, it can declare with the utmost certainty that on average, all men in this category will. These actuaries bet their...variables are manipulated and data is collected. There are abundant sources of literature on DoE that describe the mathematical and statistical based tac

Title: Studies on drug switchability showed heterogeneity in methodological approaches: a scoping review.

PubMed

Belleudi, Valeria; Trotta, Francesco; Vecchi, Simona; Amato, Laura; Addis, Antonio; Davoli, Marina

2018-05-16

Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. To conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. We searched PubMed, EMBASE, and Web of Science (updated 1/31/2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly, previous drug use and switching reasons were considered. All findings were summarized in descriptive analyses. Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular and rheumatology were the most frequently represented clinical areas. 75% of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes were measured to identify switching connected with lack of effectiveness or adverse events. This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs. Copyright © 2018. Published by Elsevier Inc.

Concordant, non-atypical breast papillomas do not require surgical excision: A 10-year multi-institution study and review of the literature.

PubMed

Grimm, Lars J; Bookhout, Christine E; Bentley, Rex C; Jordan, Sheryl G; Lawton, Thomas J

2018-05-01

Non-atypical papillomas (NAPs) diagnosed on core needle biopsy (CNB) frequently undergo surgical excision due to highly variable upstaging rates. The purpose of this study is to document our dual-institution upgrade rates of NAPs diagnosed on core needle biopsy and review the upgrade rates reported in the literature. Following IRB approval, CNB results from Duke University (7/1/2004-6/30/2014) and the University of North Carolina Chapel Hill (1/1/04-6/30/2013) were reviewed to identify non-atypical papillomas. All cases with surgical excision or 2 years of imaging follow up were included. In addition, a literature review identified 60 published studies on upgrades of NAPs diagnosed at CNB. Cases in our cohort and the published literature were reviewed for confounding factors: [1] missing radiologic-pathologic concordance and/or discordance, [2] papillomas included with high-risk lesions, [3] high risk lesions counted as upgrades, [4] review by a nonspecialized breast pathologist, and [5] cancer incidentally detected. Of the 388 CNBs in our dual-institution cohort, 136 (35%) patients underwent surgical excision and 252 (65%) patients had imaging follow up. After controlling for confounders, no cancers (0/388) were found at surgical excision or during follow up imaging. The literature review upstaging rate was 4.0% (166/4157) but 1.8% (4/227) after excluding studies with confounders. The combined upstaging rate from the literature and this study was 0.6% (4/615). The upstaging rate for CNB diagnosed NAPs was 0% in our cohort and 0.6% overall after adjusting for confounders. This low rate does not warrant reflexive surgical excision and diagnostic imaging follow up should be discretionary. Copyright © 2018 Elsevier Inc. All rights reserved.

Cannabis Use, Polysubstance Use, and Psychosis Spectrum Symptoms in a Community-Based Sample of US Youth

PubMed Central

Jones, Jason D.; Calkins, Monica E.; Scott, J. Cobb; Bach, Emily C.; Gur, Raquel E.

2017-01-01

Purpose To examine how cannabis use and polysubstance use among cannabis users relate to psychosis spectrum (PS) symptoms in a large community-based sample of US youth. Methods 4,171 youth (age 14–21; mean=16.90, SD=1.85; 55% female) from the Philadelphia Neurodevelopmental Cohort (PNC) completed assessments of substance use, PS symptoms, and confounding variables (e.g., demographics, comorbid psychopathology, trauma exposure). Results After adjusting for confounds, cannabis use by itself was not associated with increased odds of being classified as “psychosis spectrum.” However, cannabis use in combination with tobacco or other substance use was associated with increased odds of PS classification (adjusted odds ratios [ORs] = 1.37 to 1.76). Follow-up symptom-level analyses revealed that cannabis use in combination with other substances was associated with subclinical positive symptoms (ORs=1.95 and 2.24) and frequent cannabis use was associated with subclinical negative/disorganized symptoms (OR=2.14). However, these symptom-level findings were reduced to trends after correction for multiple comparisons. Neither cannabis use nor polysubstance use was associated with threshold delusions or hallucinations. Conclusions After adjusting for important confounds, there was minimal evidence for associations between cannabis use by itself and PS symptoms. More compelling evidence emerged for associations between polysubstance use among cannabis users and PS symptoms. This study highlights the importance of considering polysubstance use and confounds when examining associations between cannabis use and PS symptoms. Further longitudinal research is necessary to determine whether these findings represent causal associations or shared genetic and/or environmental vulnerability for substance use and PS symptoms. PMID:28318911

Unilateral spatial neglect in the acute phase of ischemic stroke can predict long-term disability and functional capacity.

PubMed

Luvizutto, Gustavo José; Moliga, Augusta Fabiana; Rizzatti, Gabriela Rizzo Soares; Fogaroli, Marcelo Ortolani; Moura Neto, Eduardo de; Nunes, Hélio Rubens de Carvalho; Resende, Luiz Antônio de Lima; Bazan, Rodrigo

2018-05-21

The aim of this study was to assess the relationship between the degree of unilateral spatial neglect during the acute phase of stroke and long-term functional independence. This was a prospective study of right ischemic stroke patients in which the independent variable was the degree of spatial neglect and the outcome that was measured was functional independence. The potential confounding factors included sex, age, stroke severity, topography of the lesion, risk factors, glycemia and the treatment received. Unilateral spatial neglect was measured using the line cancellation test, the star cancellation test and the line bisection test within 48 hours of the onset of symptoms. Functional independence was measured using the modified Rankin and Barthel scales at 90 days after discharge. The relationship between unilateral spatial neglect and functional independence was analyzed using multiple logistic regression that was corrected for confounding factors. We studied 60 patients with a median age of 68 (34-89) years, 52% of whom were male and 74% of whom were Caucasian. The risk for moderate to severe disability increased with increasing star cancellation test scores (OR=1.14 [1.03-1.26], p=0.01) corrected for the stroke severity, which was a confounding factor that had a statistically positive association with disability (OR=1.63 [1.13-2.65], p=0.01). The best chance of functional independence decreased with increasing star cancellation test scores (OR=0.86 [0.78-0.96], p=0.006) corrected for the stroke severity, which was a confounding factor that had a statistically negative association with independence (OR=0.66 [0.48-0.92], p=0.017). The severity of unilateral spatial neglect in acute stroke worsens the degree of long-term disability and functional independence.

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.

Cannabis Use, Polysubstance Use, and Psychosis Spectrum Symptoms in a Community-Based Sample of U.S. Youth.

PubMed

Jones, Jason D; Calkins, Monica E; Scott, J Cobb; Bach, Emily C; Gur, Raquel E

2017-06-01

To examine how cannabis use and polysubstance use among cannabis users relate to psychosis spectrum (PS) symptoms in a large community-based sample of U.S. youth. Four thousand one hundred seventy-one youths (aged 14-21 years; mean = 16.90 years, SD = 1.85; 55% female) from the Philadelphia Neurodevelopmental Cohort completed assessments of substance use, PS symptoms, and confounding variables (e.g., demographics, comorbid psychopathology, and trauma exposure). After adjusting for confounds, cannabis use by itself was not associated with increased odds of being classified as "psychosis spectrum." However, cannabis use in combination with tobacco or other substance use was associated with increased odds of PS classification (adjusted odds ratios [ORs] = 1.37-1.76). Follow-up symptom-level analyses revealed that cannabis use in combination with other substances was associated with subclinical positive symptoms (ORs = 1.95 and 2.24) and frequent cannabis use was associated with subclinical negative/disorganized symptoms (OR = 2.14). However, these symptom-level findings were reduced to trends after correction for multiple comparisons. Neither cannabis use nor polysubstance use was associated with threshold delusions or hallucinations. After adjusting for important confounds, there was minimal evidence for associations between cannabis use by itself and PS symptoms. More compelling evidence emerged for associations between polysubstance use among cannabis users and PS symptoms. This study highlights the importance of considering polysubstance use and confounds when examining associations between cannabis use and PS symptoms. Further longitudinal research is necessary to determine whether these findings represent causal associations or shared genetic and/or environmental vulnerability for substance use and PS symptoms. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Longitudinal associations of burnout with heart rate variability in patients following acute coronary syndrome: A one-year follow-up study.

PubMed

Zhang, Min; Liu, Ling; Shi, Yunke; Yang, Yanfei; Yu, Xiaoju; Angerer, Peter; Kristensen, Tage S; Li, Jian

2018-05-25

To investigate longitudinal associations of burnout with heart rate variability (HRV) in patients after their first acute coronary syndrome (ACS). Two hundred eight patients participated in this one-year follow-up study. On the day before discharge, their personal burnout level was assessed by the Copenhagen Burnout Inventory. HRV signals were collected at four time points: the day before discharge, one month, six month and one year after discharge. HRV was measured by 24-h ambulatory electrocardiography and analyzed in time and frequency domains. Generalized estimating equations were applied to analyze the associations of burnout at baseline with longitudinal tracking of HRV during follow-up. After adjusting for relevant confounding factors, high burnout at baseline was significantly associated with low SDNN, a time domain measure of HRV [regression coefficient = -0.087, 95% CI = (-0.136, -0.038) by an increase per SD in burnout score, p = 0.001]. Also, baseline burnout was inversely associated with five frequency domain measures, i.e., HF [coefficient = -0.179, 95% CI = (-0.352, -0.006), p = 0.043], LF [coefficient = -0.171, 95% CI = (-0.319, -0.023), p = 0.024], VLF [coefficient = -0.367, 95% CI = (-0.483, -0.250), p < 0.001], ULF [coefficient = -0.268, 95% CI = (-0.351, -0.184), p < 0.001], and TP [coefficient = -0.283, 95% CI = (-0.340, -0.165), p < 0.001]. Personal burnout is longitudinally associated with decreased HRV during one-year period among patients after first ACS. Copyright © 2018 Elsevier Inc. All rights reserved.

CerebroMatic: A Versatile Toolbox for Spline-Based MRI Template Creation

PubMed Central

Wilke, Marko; Altaye, Mekibib; Holland, Scott K.

2017-01-01

Brain image spatial normalization and tissue segmentation rely on prior tissue probability maps. Appropriately selecting these tissue maps becomes particularly important when investigating “unusual” populations, such as young children or elderly subjects. When creating such priors, the disadvantage of applying more deformation must be weighed against the benefit of achieving a crisper image. We have previously suggested that statistically modeling demographic variables, instead of simply averaging images, is advantageous. Both aspects (more vs. less deformation and modeling vs. averaging) were explored here. We used imaging data from 1914 subjects, aged 13 months to 75 years, and employed multivariate adaptive regression splines to model the effects of age, field strength, gender, and data quality. Within the spm/cat12 framework, we compared an affine-only with a low- and a high-dimensional warping approach. As expected, more deformation on the individual level results in lower group dissimilarity. Consequently, effects of age in particular are less apparent in the resulting tissue maps when using a more extensive deformation scheme. Using statistically-described parameters, high-quality tissue probability maps could be generated for the whole age range; they are consistently closer to a gold standard than conventionally-generated priors based on 25, 50, or 100 subjects. Distinct effects of field strength, gender, and data quality were seen. We conclude that an extensive matching for generating tissue priors may model much of the variability inherent in the dataset which is then not contained in the resulting priors. Further, the statistical description of relevant parameters (using regression splines) allows for the generation of high-quality tissue probability maps while controlling for known confounds. The resulting CerebroMatic toolbox is available for download at http://irc.cchmc.org/software/cerebromatic.php. PMID:28275348

CerebroMatic: A Versatile Toolbox for Spline-Based MRI Template Creation.

PubMed

Wilke, Marko; Altaye, Mekibib; Holland, Scott K

2017-01-01

Brain image spatial normalization and tissue segmentation rely on prior tissue probability maps. Appropriately selecting these tissue maps becomes particularly important when investigating "unusual" populations, such as young children or elderly subjects. When creating such priors, the disadvantage of applying more deformation must be weighed against the benefit of achieving a crisper image. We have previously suggested that statistically modeling demographic variables, instead of simply averaging images, is advantageous. Both aspects (more vs. less deformation and modeling vs. averaging) were explored here. We used imaging data from 1914 subjects, aged 13 months to 75 years, and employed multivariate adaptive regression splines to model the effects of age, field strength, gender, and data quality. Within the spm/cat12 framework, we compared an affine-only with a low- and a high-dimensional warping approach. As expected, more deformation on the individual level results in lower group dissimilarity. Consequently, effects of age in particular are less apparent in the resulting tissue maps when using a more extensive deformation scheme. Using statistically-described parameters, high-quality tissue probability maps could be generated for the whole age range; they are consistently closer to a gold standard than conventionally-generated priors based on 25, 50, or 100 subjects. Distinct effects of field strength, gender, and data quality were seen. We conclude that an extensive matching for generating tissue priors may model much of the variability inherent in the dataset which is then not contained in the resulting priors. Further, the statistical description of relevant parameters (using regression splines) allows for the generation of high-quality tissue probability maps while controlling for known confounds. The resulting CerebroMatic toolbox is available for download at http://irc.cchmc.org/software/cerebromatic.php.

Retrospective lifetime dietary patterns predict cognitive performance in community-dwelling older Australians.

PubMed

Hosking, Diane E; Nettelbeck, Ted; Wilson, Carlene; Danthiir, Vanessa

2014-07-28

Dietary intake is a modifiable exposure that may have an impact on cognitive outcomes in older age. The long-term aetiology of cognitive decline and dementia, however, suggests that the relevance of dietary intake extends across the lifetime. In the present study, we tested whether retrospective dietary patterns from the life periods of childhood, early adulthood, adulthood and middle age predicted cognitive performance in a cognitively healthy sample of 352 older Australian adults >65 years. Participants completed the Lifetime Diet Questionnaire and a battery of cognitive tests designed to comprehensively assess multiple cognitive domains. In separate regression models, lifetime dietary patterns were the predictors of cognitive factor scores representing ten constructs derived by confirmatory factor analysis of the cognitive test battery. All regression models were progressively adjusted for the potential confounders of current diet, age, sex, years of education, English as native language, smoking history, income level, apoE ɛ4 status, physical activity, other past dietary patterns and health-related variables. In the adjusted models, lifetime dietary patterns predicted cognitive performance in this sample of older adults. In models additionally adjusted for intake from the other life periods and mechanistic health-related variables, dietary patterns from the childhood period alone reached significance. Higher consumption of the 'coffee and high-sugar, high-fat extras' pattern predicted poorer performance on simple/choice reaction time, working memory, retrieval fluency, short-term memory and reasoning. The 'vegetable and non-processed' pattern negatively predicted simple/choice reaction time, and the 'traditional Australian' pattern positively predicted perceptual speed and retrieval fluency. Identifying early-life dietary antecedents of older-age cognitive performance contributes to formulating strategies for delaying or preventing cognitive decline.

Social roles and alcohol consumption: a study of 10 industrialised countries*

PubMed Central

Kuntsche, Sandra; Knibbe, Ronald A.; Gmel, Gerhard

2014-01-01

The empirical evidence as regards the precise association between alcohol use and social roles, and these associations across genders and cultures is heterogeneous. The literature tends to focus on two central but conflicting theories. The first - classic role theory - assumes that a higher number of social roles is associated with a more structured life and thus fewer opportunities to drink heavily. The second - the multiple burden hypothesis - posits that the increasing complexity of multiple social roles leads to higher stress levels, and thus to increased alcohol use. Survey data on 25- to 54-year olds in ten western industrialised countries which participate in the GenACIS project were used to test whether holding the three main social roles - partnership, parenthood, and paid labour - had a more protective or a more detrimental association with problematic alcohol use than holding fewer roles. Age and education were included as possible confounders, while the outcome variables were risky single occasion drinking (RSOD) and heavy-volume drinking. For both genders and in almost all countries, the study found that those who had all three roles were least likely to drink heavily or engage in RSOD, thus supporting the assumptions of classic role theory. It also found that the protective effect of multiple roles was more consistent for RSOD. There were a few countries where a two-role model gave a better fit. Results for Germany (RSOD), Switzerland, and the US (heavy volume) indicate that the role of paid labour appears to be particularly relevant for risky alcohol use among women. Despite some variability in the association between paid labour and heavy drinking or RSOD among women, in almost all countries the greater the number of roles a person held, the lower their risk of this type of alcohol use was. PMID:19232807

The reliability of using postero-anterior cephalometry and cone-beam CT to determine transverse dimensions in clinical practice.

PubMed

Tai, Benjamin; Goonewardene, Mithran Suresh; Murray, Kevin; Koong, Bernard; Islam, Syed Mohammed Shamsul

2014-11-01

This study primarily aimed to assess the accuracy of classically-advocated reference points for the measurement of transverse jaw-base and dental relationships using conventional Postero-Anterior Cephalometry (PAC) and Cone-Beam Computed Tomography (CBCT). PAC and CBCT images were collected from 31 randomly selected orthodontic patients (12 males, 19 females), all of whom had a full permanent dentition. The transverse widths of the maxilla, mandible and the dentition were measured using reference points on both image modalities. Confidence intervals, intra-class coefficients and Bland Altman plots were used to assess the measurement differences derived from the two acquirement methods. Measurements on PAC and CBCT images demonstrated statistically significant differences in the majority of the assessed variables. The interjugal (J-J) width was one of only two variables which did not demonstrate a statistically significant difference on image comparison. The mean differences of the antegonial width (Ag-Ag) (-4.44mm, 95% CI -5.38 to -3.51) represented the greatest difference between the imaging techniques. The application of these points to a transverse skeletal analysis (J-J/Ag-Ag ratio) revealed that five of the 31 subjects (16%) recorded 'false positive' readings according to the derived data. It is recommended that clinicians are cautious when interpreting and making decisions related to transverse dimensions derived from a PAC. The PAC has a higher tendency to falsely identify individuals who require maxillary expansion procedures based on conventional clinical criteria. The errors primarily associated with identifying structures which represent the width of the mandible are significant in both PAC and CBCT techniques and require further investigation. It is postulated that the confounding effects of overlying soft tissues have a sianificant impact on a clinician's ability to identify relevant landmarks.

Family pet ownership during childhood: findings from a UK birth cohort and implications for public health research.

PubMed

Westgarth, Carri; Heron, Jon; Ness, Andy R; Bundred, Peter; Gaskell, Rosalind M; Coyne, Karen P; German, Alexander J; McCune, Sandra; Dawson, Susan

2010-10-01

In developed nations, approximately half of household environments contain pets. Studies of Human-Animal Interaction (HAI) have proposed that there are health benefits and risks associated with pet ownership. However, accurately demonstrating and understanding these relationships first requires a better knowledge of factors associated with ownership of different pet types. A UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were used to collect pet ownership data from the mothers, from gestation to child age 10 years old. 14,663 children were included in the study, of which mothers of 13,557 reported pet information at gestation, and 7,800 by age 10. Pet types recorded include cat, dog, rabbit, rodent, bird, fish and tortoise/turtle. The dataset also contains a number of demographic, socioeconomic and behavioural variables relevant to human health behaviour. Logistic regression was used to build multivariable models for ownership of each pet type at age 7 years. Family pet ownership increased during childhood, in particular rabbits, rodents and fish. A number of socioeconomic and demographic factors were associated with ownership of different pet types and the effects differed depending on the pet type studied. Variables which require consideration by researchers include gender, presence of older siblings, ethnicity, maternal and paternal education, maternal and paternal social class, maternal age, number of people in the household, house type, and concurrent ownership of other pets. Whether the mother had pets during her childhood was a strong predictor of pet ownership in all models. In HAI studies, care should be taken to control for confounding factors, and to treat each pet type individually. ALSPAC and other similar birth cohorts can be considered a potential resource for research into the effects of pet ownership during childhood.

Family Pet Ownership during Childhood: Findings from a UK Birth Cohort and Implications for Public Health Research

PubMed Central

Westgarth, Carri; Heron, Jon; Ness, Andy R.; Bundred, Peter; Gaskell, Rosalind M.; Coyne, Karen P.; German, Alexander J.; McCune, Sandra; Dawson, Susan

2010-01-01

In developed nations, approximately half of household environments contain pets. Studies of Human-Animal Interaction (HAI) have proposed that there are health benefits and risks associated with pet ownership. However, accurately demonstrating and understanding these relationships first requires a better knowledge of factors associated with ownership of different pet types. A UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were used to collect pet ownership data from the mothers, from gestation to child age 10 years old. 14,663 children were included in the study, of which mothers of 13,557 reported pet information at gestation, and 7,800 by age 10. Pet types recorded include cat, dog, rabbit, rodent, bird, fish and tortoise/turtle. The dataset also contains a number of demographic, socioeconomic and behavioural variables relevant to human health behaviour. Logistic regression was used to build multivariable models for ownership of each pet type at age 7 years. Family pet ownership increased during childhood, in particular rabbits, rodents and fish. A number of socioeconomic and demographic factors were associated with ownership of different pet types and the effects differed depending on the pet type studied. Variables which require consideration by researchers include gender, presence of older siblings, ethnicity, maternal and paternal education, maternal and paternal social class, maternal age, number of people in the household, house type, and concurrent ownership of other pets. Whether the mother had pets during her childhood was a strong predictor of pet ownership in all models. In HAI studies, care should be taken to control for confounding factors, and to treat each pet type individually. ALSPAC and other similar birth cohorts can be considered a potential resource for research into the effects of pet ownership during childhood. PMID:21139856

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.

Color discrimination errors associate with axial motor impairments in Parkinson's disease.

PubMed

Bohnen, Nicolaas I; Haugen, Jacob; Ridder, Andrew; Kotagal, Vikas; Albin, Roger L; Frey, Kirk A; Müller, Martijn L T M

2017-01-01

Visual function deficits are more common in imbalance-predominant compared to tremor-predominant PD suggesting a pathophysiological role of impaired visual functions in axial motor impairments. To investigate the relationship between changes in color discrimination and motor impairments in PD while accounting for cognitive or other confounder factors. PD subjects (n=49, age 66.7±8.3 years; Hoehn & Yahr stage 2.6±0.6) completed color discrimination assessment using the Farnsworth-Munsell 100 Hue Color Vision Test, neuropsychological, motor assessments and [ 11 C]dihydrotetrabenazine vesicular monoamine transporter type 2 PET imaging. MDS-UPDRS sub-scores for cardinal motor features were computed. Timed up and go mobility and walking tests were assessed in 48 subjects. Bivariate correlation coefficients between color discrimination and motor variables were significant only for the Timed up and go (R S =0.44, P=0.0018) and the MDS-UPDRS axial motor scores (R S =0.38, P=0.0068). Multiple regression confounder analysis using the Timed up and go as outcome parameter showed a significant total model (F (5,43) = 7.3, P<0.0001) with significant regressor effects for color discrimination (standardized β=0.32, t=2.6, P=0.012), global cognitive Z-score (β=-0.33, t=-2.5, P=0.018), duration of disease (β=0.26, t=1.8, P=0.038), but not for age or striatal dopaminergic binding. The color discrimination test was also a significant independent regressor in the MDS-UPDRS axial motor model (standardized β=0.29, t=2.4, P=0.022; total model t (5,43) = 6.4, P=0.0002). Color discrimination errors associate with axial motor features in PD independent of cognitive deficits, nigrostriatal dopaminergic denervation, and other confounder variables. These findings may reflect shared pathophysiology between color discrimination visual impairments and axial motor burden in PD.

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

Perceived reciprocity in social exchange and health functioning in early old age: prospective findings from the GAZEL study.

PubMed

Wahrendorf, Morten; Ribet, Celine; Zins, Marie; Goldberg, Marcel; Siegrist, Johannes

2010-05-01

To assess prospectively the effects of perceived non-reciprocity of exchange in three different types of social engagement on health functioning in early old age. In the frame of the prospective French GAZEL cohort study, data on reciprocity in three types of role-related social engagement (principal regular activity in everyday life, marital role relationship, trusting relationships in civic life) were collected from 8679 men and 2742 women (mean age: 60.4 years) in 2005. Two years later, health functioning was assessed using the SF-36 mental and physical component scores, as well as self-perceived health. Multivariate regressions were calculated, controlling for important confounders including baseline self-perceived health. Consistent effects of perceived non-reciprocity in all three types of social exchange on mental and physical health functioning were observed. After adjustment for relevant confounders including baseline self-perceived, health effects were attenuated, but largely remained significant. Findings underline the importance of the quality of social exchange (reciprocity vs. non-reciprocity) for health functioning in early old age.

Random measurement error: Why worry? An example of cardiovascular risk factors.

PubMed

Brakenhoff, Timo B; van Smeden, Maarten; Visseren, Frank L J; Groenwold, Rolf H H

2018-01-01

With the increased use of data not originally recorded for research, such as routine care data (or 'big data'), measurement error is bound to become an increasingly relevant problem in medical research. A common view among medical researchers on the influence of random measurement error (i.e. classical measurement error) is that its presence leads to some degree of systematic underestimation of studied exposure-outcome relations (i.e. attenuation of the effect estimate). For the common situation where the analysis involves at least one exposure and one confounder, we demonstrate that the direction of effect of random measurement error on the estimated exposure-outcome relations can be difficult to anticipate. Using three example studies on cardiovascular risk factors, we illustrate that random measurement error in the exposure and/or confounder can lead to underestimation as well as overestimation of exposure-outcome relations. We therefore advise medical researchers to refrain from making claims about the direction of effect of measurement error in their manuscripts, unless the appropriate inferential tools are used to study or alleviate the impact of measurement error from the analysis.

Single living predicts a higher mortality in both women and men with chronic heart failure.

PubMed

Mard, Shan; Nielsen, Finn Erland

2016-09-01

We examined the impact of single living on all-cause mortality in patients with chronic heart failure and determined if this association was modified by gender. This historical cohort study included 637 patients who were admitted to the Department of Cardiology, Herlev Hospital, Denmark, between 1 July 2005 and 30 June 2007. Baseline clinical data were obtained from patient records. Data on survival rates were obtained from the Danish Civil Registration System. Cox proportional hazard analysis was used to compute the hazard ratio (HR) of all-cause mortality, controlling for confounding factors. The median follow-up time was 2.8 years. A total of 323 (50.7%) patients died during the follow-up period. After adjustment for confounding factors, risk of death was associated with being single (HR = 1.53 (95% confidence interval: 1.19-1.96)). In a gender-stratified analysis, the risk of death did not differ among single-living women and men. Single living is a prognostic determinant of all-cause mortality in men and women with chronic heart failure. none. not relevant.

Daily commuting to work is not associated with variables of health.

PubMed

Mauss, Daniel; Jarczok, Marc N; Fischer, Joachim E

2016-01-01

Commuting to work is thought to have a negative impact on employee health. We tested the association of work commute and different variables of health in German industrial employees. Self-rated variables of an industrial cohort (n = 3805; 78.9 % male) including absenteeism, presenteeism and indices reflecting stress and well-being were assessed by a questionnaire. Fasting blood samples, heart-rate variability and anthropometric data were collected. Commuting was grouped into one of four categories: 0-19.9, 20-44.9, 45-59.9, ≥60 min travelling one way to work. Bivariate associations between commuting and all variables under study were calculated. Linear regression models tested this association further, controlling for potential confounders. Commuting was positively correlated with waist circumference and inversely with triglycerides. These associations did not remain statistically significant in linear regression models controlling for age, gender, marital status, and shiftwork. No other association with variables of physical, psychological, or mental health and well-being could be found. The results indicate that commuting to work has no significant impact on well-being and health of German industrial employees.

An hourly variation in zoo visitor interest: measurement and significance for animal welfare research.

PubMed

Davey, Gareth

2006-01-01

A methodological difficulty facing welfare research on nonhuman animals in the zoo is the large number of uncontrolled variables due to variation within and between study sites. Zoo visitors act as uncontrolled variables, with number, density, size, and behavior constantly changing. This is worrisome because previous research linked visitor variables to animal behavioral changes indicative of stress. There are implications for research design: Studies not accounting for visitors' effect on animal welfare risk confounding (visitor) variables distorting their findings. Zoos need methods to measure and minimize effects of visitor behavior and to ensure that there are no hidden variables in research models. This article identifies a previously unreported variable--hourly variation (decrease) in visitor interest--that may impinge on animal welfare and validates a methodology for measuring it. That visitor interest wanes across the course of the day has important implications for animal welfare management; visitor effects on animal welfare are likely to occur, or intensify, during the morning or in earlier visits when visitor interest is greatest. This article discusses this issue and possible solutions to reduce visitor effects on animal well-being.

T-wave alternans and beat-to-beat variability of repolarization: pathophysiological backgrounds and clinical relevance.

PubMed

Floré, Vincent; Willems, Rik

2012-12-01

In this review, we focus on temporal variability of cardiac repolarization. This phenomenon has been related to a higher risk for ventricular arrhythmia and is therefore interesting as a marker of sudden cardiac death risk. We review two non-invasive clinical techniques quantifying repolarization variability: T-wave alternans (TWA) and beat-to-beat variability of repolarization (BVR). We discuss their pathophysiological link with ventricular arrhythmia and the current clinical relevance of these techniques.

Separating decadal global water cycle variability from sea level rise.

PubMed

Hamlington, B D; Reager, J T; Lo, M-H; Karnauskas, K B; Leben, R R

2017-04-20

Under a warming climate, amplification of the water cycle and changes in precipitation patterns over land are expected to occur, subsequently impacting the terrestrial water balance. On global scales, such changes in terrestrial water storage (TWS) will be reflected in the water contained in the ocean and can manifest as global sea level variations. Naturally occurring climate-driven TWS variability can temporarily obscure the long-term trend in sea level rise, in addition to modulating the impacts of sea level rise through natural periodic undulation in regional and global sea level. The internal variability of the global water cycle, therefore, confounds both the detection and attribution of sea level rise. Here, we use a suite of observations to quantify and map the contribution of TWS variability to sea level variability on decadal timescales. In particular, we find that decadal sea level variability centered in the Pacific Ocean is closely tied to low frequency variability of TWS in key areas across the globe. The unambiguous identification and clean separation of this component of variability is the missing step in uncovering the anthropogenic trend in sea level and understanding the potential for low-frequency modulation of future TWS impacts including flooding and drought.

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.

Relaxing the rule of ten events per variable in logistic and Cox regression.

PubMed

Vittinghoff, Eric; McCulloch, Charles E

2007-03-15

The rule of thumb that logistic and Cox models should be used with a minimum of 10 outcome events per predictor variable (EPV), based on two simulation studies, may be too conservative. The authors conducted a large simulation study of other influences on confidence interval coverage, type I error, relative bias, and other model performance measures. They found a range of circumstances in which coverage and bias were within acceptable levels despite less than 10 EPV, as well as other factors that were as influential as or more influential than EPV. They conclude that this rule can be relaxed, in particular for sensitivity analyses undertaken to demonstrate adequate control of confounding.

Spatial variation in attributable risks.

PubMed

Congdon, Peter

2015-01-01

The attributable risk (AR) measures the contribution of a particular risk factor to a disease, and allows estimation of disease rates specific to that risk. While previous studies consider variability in ARs over demographic categories, this paper considers the extent of spatial variability in ARs estimated from multilevel data with confounders both at individual and geographic levels. A case study considers the AR for diabetes in relation to elevated BMI, and area rates for diabetes attributable to excess weight. Contextual adjustment includes known area variables, and unobserved spatially clustered influences, while spatial heterogeneity (effect modification) is considered in terms of varying effects of elevated BMI by neighbourhood deprivation category. The application is to patient register data in London, with clear evidence of spatial variation in ARs, and in small area diabetes rates attributable to excess weight. Copyright © 2015 Elsevier Ltd. All rights reserved.

When to trust our learners? Clinical teachers' perceptions of decision variables in the entrustment process.

PubMed

Duijn, Chantal C M A; Welink, Lisanne S; Bok, Harold G J; Ten Cate, Olle T J

2018-06-01

Clinical training programs increasingly use entrustable professional activities (EPAs) as focus of assessment. However, questions remain about which information should ground decisions to trust learners. This qualitative study aimed to identify decision variables in the workplace that clinical teachers find relevant in the elaboration of the entrustment decision processes. The findings can substantiate entrustment decision-making in the clinical workplace. Focus groups were conducted with medical and veterinary clinical teachers, using the structured consensus method of the Nominal Group Technique to generate decision variables. A ranking was made based on a relevance score assigned by the clinical teachers to the different decision variables. Field notes, audio recordings and flip chart lists were analyzed and subsequently translated and, as a form of axial coding, merged into one list, combining the decision variables that were similar in their meaning. A list of 11 and 17 decision variables were acknowledged as relevant by the medical and veterinary teacher groups, respectively. The focus groups yielded 21 unique decision variables that were considered relevant to inform readiness to perform a clinical task on a designated level of supervision. The decision variables consisted of skills, generic qualities, characteristics, previous performance or other information. We were able to group the decision variables into five categories: ability, humility, integrity, reliability and adequate exposure. To entrust a learner to perform a task at a specific level of supervision, a supervisor needs information to support such a judgement. This trust cannot be credited on a single case at a single moment of assessment, but requires different variables and multiple sources of information. This study provides an overview of decision variables giving evidence to justify the multifactorial process of making an entrustment decision.

Conditioned Stimuli’s Role in Relapse: Pre-Clinical Research on Pavlovian Instrumental Transfer

PubMed Central

Lamb, R.J.; Schindler, W.; Pinkston, Jonathan W.

2016-01-01

Rationale and Objective Pavlovian learning is central to many theories of addiction. In these theories, stimuli paired with drug ingestion become Conditioned Stimuli (CS) and subsequently elicit drug-seeking and -taking. However in most relevant studies, Pavlovian and instrumental learning are confounded. This confound may be avoided in Pavlovian-Instrumental-Transfer (PIT) procedures. In PIT, Pavlovian and instrumental learning are established separately, and then combined. In order to better understand the role of CSs in addiction, we review the relevant studies using PIT. Findings We identified seven articles examining PIT effects of ethanol- or cocaine-paired CSs. Under at least one condition six of these articles reported CS-elicited increases in responding previously maintained by drug. However, the only study using the optimal control condition failed to find a CS-elicited increase. Two studies examining CS specificity found the CS also increased responding maintained by a different reinforcer. Two studies examined if CSs elicit increases in actual drug-taking. Both failed to find CS-elicited increases, i.e., no study shows CS-elicited increases in actual drug-taking. Further, CS-elicited increases in extinguished responding are short-lived. Conclusions These findings are not entirely consistent with Pavlovian learning playing a central role in addiction. However, design issues can explain most of these inconsistencies. Studies without these design issues are needed. Additionally, existing theories hypothesize drug-paired CSs increase drug-taking by increasing motivation, by eliciting conditioned responses that make drug-seeking more probable, or by a combination of these. Work distinguishing between these mechanisms would also be useful. PMID:26800688

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

PubMed

Zampieri, Fernando G; Póvoa, Pedro; Salluh, Jorge I; Rodriguez, Alejandro; Valade, Sandrine; Andrade Gomes, José; Reignier, Jean; Molinos, Elena; Almirall, Jordi; Boussekey, Nicolas; Socias, Lorenzo; Ramirez, Paula; Viana, William N; Rouzé, Anahita; Nseir, Saad; Martin-Loeches, Ignacio

2018-01-01

To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Overview of clinical research design.

PubMed

Hartung, Daniel M; Touchette, Daniel

2009-02-15

Basic concepts and terminology of clinical research design are presented for new clinical investigators. Clinical research, research involving human subjects, can be described as either observational or experimental. The findings of all clinical research can be threatened by issues of bias and confounding. Biases are systematic errors in how study subjects are selected or measured, which result in false inferences. Confounding is a distortion in findings that is attributable to mixing variable effects. Uncontrolled observation research is generally more prone to bias and confounding than experimental research. Observational research includes designs such as the cohort study, case-control study, and cross-sectional study, while experimental research typically involves a randomized controlled trial (RCT). The cohort study, which includes the RCT, defines subject allocation on the basis of exposure interest (e.g., drug, disease-management program) and follows the patients to assess the outcomes. The case-control study uses the primary outcome of interest (e.g., adverse event) to define subject allocation, and different exposures are assessed in a retrospective manner. Cross-sectional research evaluates both exposure and outcome concurrently. Each of these design methods possesses different strengths and weaknesses in answering research questions, as well as underlying many study subtypes. While experimental research is the strongest method for establishing causality, it can be difficult to accomplish under many scenarios. Observational clinical research offers many design alternatives that may be appropriate if planned and executed carefully.

Dietary protein intakes and risk of ulcerative colitis.

PubMed

Rashvand, Samaneh; Somi, Mohammad Hossein; Rashidkhani, Bahram; Hekmatdoost, Azita

2015-01-01

The incidence of ulcerative colitis (UC) is rising in populations with western-style diet, rich in fat and protein, and low in fruits and vegetables. In the present study, we aimed to evaluate the association between dietary protein intakes and the risk of developing incident UC. Sixty two cases of UC and 124 controls were studied using country-specific food frequency questionnaire (FFQ). Group comparisons by each factor were done using χ2 test, and significance level was set at α= 0.05. Logistic regression adjusted for potential confounding variables was carried out. Univariate analysis suggested positive associations between processed meat, red meat and organ meat with risk of ulcerative colitis. Comparing highest versus lowest categories of consumption, multivariate conditional logistic regression analysis accounting for potential confounding variables indicated that patients who consumed a higher amount of processed meat were at a higher risk for developing UC (P value for trend= 0.02). Similarly, patients who consumed higher amounts of red meat were at a higher risk for UC (P value for trend= 0.01). The highest tertile of intake of organ meat was associated with an increased risk of ulcerative colitis with a statistically significant trend across tertiles (P value for trend= 0.01) when adjusted. In this case-control study we observed that higher consumptions of processed meat, red meat and organ meat were associated with increased risk for UC.

Understanding Cataract Risk in Aerospace Flight Crew And Review of Mechanisms of Cataract Formation

NASA Technical Reports Server (NTRS)

Jones, Jeffrey A.; McCarten, M.; Manuel, K.; Djojonegoro, B.; Murray, J.; Cucinotta, F.; Feiversen, A.; Wear, M.

2006-01-01

Induction of cataracts by occupational exposure in flight crew has been an important topic of interest in aerospace medicine in the past five years, in association with numerous reports of flight-associated disease incidences. Due to numerous confounding variables, it has been difficult to determine if there is increased cataract risk directly caused by interaction with the flight environment, specifically associated with added radiation exposure during flight. Military aviator records from the United States Air Force (USAF) and Navy (USN) and US astronauts at the National Aeronautics and Space Administration (NASA)/Lyndon B. Johnson Space Center (JSC) were evaluated for the presence, location and age of diagnosis of cataracts. Military aviators were found to have a statistically significant younger average age of onset of their cataracts compared with astronauts, however the incidence density of cataracts was found to be statistically higher in astronauts than in military aviators. USAF and USN aviator s cataracts were most commonly located in the posterior subcapsular region of the lens while astronauts cataracts were most likely to originate generally in the cortical zone. A prospective clinical trial which controls for confounding variables in examination technique, cataract classification, diet, exposure, and pharmacological intervention is needed to determine what percentage of the risk for cataracts are due to radiation, and how to best develop countermeasures to protect flight crews from radiation bioeffects in the future.

Abnormal vaginal colonization by gram-negative bacteria is significantly higher in pregnancy conceived through infertility treatment compared to natural pregnancy.

PubMed

Kim, Ji Y; Sung, Ji-Hee; Chang, Kylie Hae-Jin; Choi, Suk-Joo; Oh, Soo-Young; Roh, Cheong-Rae; Kim, Jong-Hwa

2017-03-01

To compare abnormal vaginal colonization between natural pregnancy and pregnancy by infertility treatment in high-risk parturient women and to examine the association between abnormal vaginal colonization and early-onset neonatal sepsis (EONS). The clinical characteristics, vaginal culture result, and delivery outcome of patients who admitted to our high-risk unit between 2005 and 2014 were retrospectively reviewed and compared. We investigated the prevalence of EONS according to maternal vaginal colonization and examined the concordance between maternal vaginal bacteria and etiologic microorganism causing EONS. Among 1096 pregnancies, the rate of vaginal colonization by gram-negative bacteria, especially Escherichia coli was significantly higher in pregnancies by infertility treatment after adjustment of confounding variables (E. coli, OR [95% CI]: 2.47 [1.33-4.57], p = 0.004). The rate of EONS was significantly higher in neonates with maternal abnormal vaginal bacteria colonization (OR [95% CI]: 3.38 [1.44-7.93], p = 0.005) after adjusting for confounding variables. Notably, among microorganisms isolated from maternal vagina, E. coli and Staphylococcus aureus were consistent with the results from neonatal blood culture in EONS. Our data implicate a possible association between gram-negative bacteria colonization and infertility treatment and suggest that maternal vaginal colonization may be associated with EONS of neonates in high-risk pregnancy.

Embryo transfer by reproductive endocrinology fellows vs attending physicians: are live birth rates comparable?

PubMed

Eaton, Jennifer L; Zhang, Xingqi; Barnes, Randall B

2014-11-01

To compare live birth rates following ultrasound-guided embryo transfer (ET) by reproductive endocrinology and infertility fellows versus attending physicians. Women who underwent their first day-3, fresh, nondonor ET between Oct. 1, 2005, and April 1, 2011, at our academic center were included in this retrospective cohort study. Embryos were designated high quality if they had 8 cells, less than 10% fragmentation, and no asymmetry. ET was performed with the afterload technique under ultrasound guidance. Categorical variables were evaluated with the χ(2) test and continuous variables with the Student t test. Logistic regression was performed to assess the relationship between ET physician and live birth rate while adjusting for potential confounders. Seven hundred sixty women underwent ET by an attending physician, and 104 by a fellow. Baseline characteristics were similar between the groups. The live birth rate was 31% following ET by an attending physician, compared with 34% following ET by a fellow (P = .65). Logistic regression adjusting for potential confounders demonstrated no significant association between ET physician and live birth rate. This retrospective study demonstrated no significant difference in live birth rates following ultrasound-guided ET by fellows vs attending physicians at our institution. These data suggest that academic practices using the afterload method and ultrasound guidance can train fellows to perform ET without compromising success rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma 17-alpha-OH-progesterone in female workers exposed to urban pollutants.

PubMed

Ciarrocca, M; Cerratti, D; Capozzella, A; Rosati, M V; Anzani, M F; Bernardini, A; Casale, T; Pimpinella, B; Tomei, G; Monti, C; Tomao, E; Tomei, F

2006-01-01

The aim of this study is to evaluate whether occupational exposure to urban pollutants could cause alteration in plasma 17-alpha-OH-P levels in female workers. After excluding the subjects with the principal confounding factors, traffic police and controls were matched by age, working life, age of menarche, menstrual cycle day, BMI, drinking habits, habitual consumption of soy and Italian coffee. 68 traffic police and 82 controls (7th day; follicular phase of the ovarian cycle), 37 traffic police and 20 controls (21st day; lutheal phase of the ovarian cycle) were included in the study and matched for the above mentioned variables. In follicular and lutheal phase of ovarian cycle, 17-alpha-OH-P mean levels and the distribution of 17-alpha-OH-P values were significantly higher in traffic police vs. controls. A higher instance of mental health disorders in traffic police vs. controls was found, although the difference was not significant. Considering that the potential confounding effect of extraneous factors was controlled by restricting the study population and by matching traffic police vs. controls on the above mentioned variables, our results suggest that occupational exposure to urban pollutants may alter plasma 17-alpha-OH-P concentrations. 17-alpha-OH-P could be used in an occupational setting as an early biomarker of exposure to urban pollutants, valuable for a group, even before the onset of related pathologies.

Home exercises for pelvic floor in continent women one year after physical therapy treatment for urinary incontinence: an observational study.

PubMed

Krüger, Ana P; Luz, Soraia C T; Virtuoso, Janeisa F

2011-01-01

To describe the results of home exercise targeting the pelvic floor in continent women one year after the end of a physical therapy treatment for the following outcomes: functional assessment of the pelvic floor and urinary incontinence. This is an observational study that evaluated fifteen women one year after physical therapy treatment for Stress Urinary Incontinence (SUI). The outcomes for this study were: situations of urinary loss, use of daily protection, practice of home exercises for the pelvic floor, functional assessment of the pelvic floor (FAPF) and patient satisfaction. We also investigated some confounding variables such as hormonal status, number of vaginal deliveries and previous history of episiotomy. One year after completion of physical therapy treatment, we observed that the FAPF median remained stable over time (Median=5, p=0.08). The presence of urinary incontinence was reported by 40% of women in the sample, however, was characterized as mild (i.e. not requiring the use of daily protection). There was also a significant association (p=0.001) between the completion of home exercises (twice or more per week) and the normal clinical status. Confounding variables, which could compromise the clinical status, showed no significant association with the outcomes (p≥0.05). Home exercises contributed to the maintenance of continence following a physical therapy treatment.

Long term effects of traffic noise on mortality in the city of Barcelona, 2004-2007.

PubMed

Barceló, Maria Antònia; Varga, Diego; Tobias, Aurelio; Diaz, Julio; Linares, Cristina; Saez, Marc

2016-05-01

Numerous studies showing statistically significant associations between environmental noise and adverse health effects already exist for short-term (over one day at most) and long-term (over a year or more) noise exposure, both for morbidity and (albeit to a lesser extent) mortality. Recently, several studies have shown this association to be independent from confounders, mainly those of air pollutants. However, what has not been addressed is the problem of misalignment (i.e. the exposure data locations and health outcomes have different spatial locations). Without any explicit control of such misalignment inference is seriously compromised. Our objective is to assess the long-term effects of traffic noise on mortality in the city of Barcelona (Spain) during 2004-2007. We take into account the control of confounding, for both air pollution and socioeconomic factors at a contextual level and, in particular, we explicitly address the problem of misalignment. We employed a case-control design with individual data. We used deaths resulting from myocardial infarction, hypertension, or Type II diabetes mellitus in Barcelona between 2004 and 2007 as cases for the study, while for controls we used deaths (likewise in Barcelona and over the same period of time) resulting from AIDS or external causes (e.g. accidental falls, accidental poisoning by psychotropic drugs, drugs of abuse, suicide and self-harm, or injuries resulting from motor vehicle accidents). The controls were matched with the cases by sex and age. We used the annual average equivalent A-weighted sound pressure levels for daytime (7-21h), evening-time (21-23h) and night-time (23-7h), and controlled for the following confounders: i) air pollutants (NO2, PM10 and benzene), ii) material deprivation (at a census tract level) and iii) land use and other spatial variables. We explicitly controlled for heterogeneity (uneven distribution of both response and environmental exposures within an area), spatial dependency (of the observations of the response variables), temporal trends (long-term behaviour of the response variables) and spatial misalignment (between response and environmental exposure locations). We used a fully Bayesian method, through the Integrated Nested Laplace Approximation (INLA). Specifically, we plugged the whole model for the exposure into the health model and obtained a linear predictor defined on the entire spatial domain. Separate analyses were carried out for men and for women. After adjusting for confounders, we found that traffic noise was associated with myocardial infarction mortality along with Type II diabetes mellitus in men (in both cases, odds ratios (OR) were around 1.02) and mortality from hypertension in women (ORs around 1.01). Nevertheless, only in the case of hypertension in women, does the association remain statistically significant for all age groups considered (all ages, ≥65 years and ≥75 years). Copyright © 2016 Elsevier Inc. All rights reserved.

Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies.

PubMed

Flegr, Jaroslav; Lindová, Jitka; Pivoñková, Vera; Havlícek, Jan

2008-12-01

A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence. (c) 2008 Wiley-Liss, Inc.

Spatial Variability of Geriatric Depression Risk in a High-Density City: A Data-Driven Socio-Environmental Vulnerability Mapping Approach.

PubMed

Ho, Hung Chak; Lau, Kevin Ka-Lun; Yu, Ruby; Wang, Dan; Woo, Jean; Kwok, Timothy Chi Yui; Ng, Edward

2017-08-31

Previous studies found a relationship between geriatric depression and social deprivation. However, most studies did not include environmental factors in the statistical models, introducing a bias to estimate geriatric depression risk because the urban environment was found to have significant associations with mental health. We developed a cross-sectional study with a binomial logistic regression to examine the geriatric depression risk of a high-density city based on five social vulnerability factors and four environmental measures. We constructed a socio-environmental vulnerability index by including the significant variables to map the geriatric depression risk in Hong Kong, a high-density city characterized by compact urban environment and high-rise buildings. Crude and adjusted odds ratios (ORs) of the variables were significantly different, indicating that both social and environmental variables should be included as confounding factors. For the comprehensive model controlled by all confounding factors, older adults who were of lower education had the highest geriatric depression risks (OR: 1.60 (1.21, 2.12)). Higher percentage of residential area and greater variation in building height within the neighborhood also contributed to geriatric depression risk in Hong Kong, while average building height had negative association with geriatric depression risk. In addition, the socio-environmental vulnerability index showed that higher scores were associated with higher geriatric depression risk at neighborhood scale. The results of mapping and cross-section model suggested that geriatric depression risk was associated with a compact living environment with low socio-economic conditions in historical urban areas in Hong Kong. In conclusion, our study found a significant difference in geriatric depression risk between unadjusted and adjusted models, suggesting the importance of including environmental factors in estimating geriatric depression risk. We also developed a framework to map geriatric depression risk across a city, which can be used for identifying neighborhoods with higher risk for public health surveillance and sustainable urban planning.

Association of Body Mass Index with Depression, Anxiety and Suicide—An Instrumental Variable Analysis of the HUNT Study

PubMed Central

Bjørngaard, Johan Håkon; Carslake, David; Lund Nilsen, Tom Ivar; Linthorst, Astrid C. E.; Davey Smith, George; Gunnell, David; Romundstad, Pål Richard

2015-01-01

Objective While high body mass index is associated with an increased risk of depression and anxiety, cumulative evidence indicates that it is a protective factor for suicide. The associations from conventional observational studies of body mass index with mental health outcomes are likely to be influenced by reverse causality or confounding by ill-health. In the present study, we investigated the associations between offspring body mass index and parental anxiety, depression and suicide in order to avoid problems with reverse causality and confounding by ill-health. Methods We used data from 32,457 mother-offspring and 27,753 father-offspring pairs from the Norwegian HUNT-study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and suicide death from national registers. Associations between offspring and own body mass index and symptoms of anxiety and depression and suicide mortality were estimated using logistic and Cox regression. Causal effect estimates were estimated with a two sample instrument variable approach using offspring body mass index as an instrument for parental body mass index. Results Both own and offspring body mass index were positively associated with depression, while the results did not indicate any substantial association between body mass index and anxiety. Although precision was low, suicide mortality was inversely associated with own body mass index and the results from the analysis using offspring body mass index supported these results. Adjusted odds ratios per standard deviation body mass index from the instrumental variable analysis were 1.22 (95% CI: 1.05, 1.43) for depression, 1.10 (95% CI: 0.95, 1.27) for anxiety, and the instrumental variable estimated hazard ratios for suicide was 0.69 (95% CI: 0.30, 1.63). Conclusion The present study’s results indicate that suicide mortality is inversely associated with body mass index. We also found support for a positive association between body mass index and depression, but not for anxiety. PMID:26167892

Association of Body Mass Index with Depression, Anxiety and Suicide-An Instrumental Variable Analysis of the HUNT Study.

PubMed

Bjørngaard, Johan Håkon; Carslake, David; Lund Nilsen, Tom Ivar; Linthorst, Astrid C E; Davey Smith, George; Gunnell, David; Romundstad, Pål Richard

2015-01-01

While high body mass index is associated with an increased risk of depression and anxiety, cumulative evidence indicates that it is a protective factor for suicide. The associations from conventional observational studies of body mass index with mental health outcomes are likely to be influenced by reverse causality or confounding by ill-health. In the present study, we investigated the associations between offspring body mass index and parental anxiety, depression and suicide in order to avoid problems with reverse causality and confounding by ill-health. We used data from 32,457 mother-offspring and 27,753 father-offspring pairs from the Norwegian HUNT-study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and suicide death from national registers. Associations between offspring and own body mass index and symptoms of anxiety and depression and suicide mortality were estimated using logistic and Cox regression. Causal effect estimates were estimated with a two sample instrument variable approach using offspring body mass index as an instrument for parental body mass index. Both own and offspring body mass index were positively associated with depression, while the results did not indicate any substantial association between body mass index and anxiety. Although precision was low, suicide mortality was inversely associated with own body mass index and the results from the analysis using offspring body mass index supported these results. Adjusted odds ratios per standard deviation body mass index from the instrumental variable analysis were 1.22 (95% CI: 1.05, 1.43) for depression, 1.10 (95% CI: 0.95, 1.27) for anxiety, and the instrumental variable estimated hazard ratios for suicide was 0.69 (95% CI: 0.30, 1.63). The present study's results indicate that suicide mortality is inversely associated with body mass index. We also found support for a positive association between body mass index and depression, but not for anxiety.

Brain natriuretic peptide in patients with congestive heart failure and central sleep apnea.

PubMed

Carmona-Bernal, Carmen; Quintana-Gallego, Esther; Villa-Gil, Manuel; Sánchez-Armengol, Angeles; Martínez-Martínez, Angel; Capote, Francisco

2005-05-01

To assess the possible relationship between Cheyne-Stokes respiration (CSR) associated with central sleep apnea (CSA) syndrome and brain natriuretic peptide (BNP) in an outpatient population presenting with stable congestive heart failure (CHF). Ninety patients with CHF due to systolic dysfunction (left ventricular ejection fraction

Spatial Variability of Geriatric Depression Risk in a High-Density City: A Data-Driven Socio-Environmental Vulnerability Mapping Approach

PubMed Central

Lau, Kevin Ka-Lun; Yu, Ruby; Wang, Dan; Kwok, Timothy Chi Yui; Ng, Edward

2017-01-01

Previous studies found a relationship between geriatric depression and social deprivation. However, most studies did not include environmental factors in the statistical models, introducing a bias to estimate geriatric depression risk because the urban environment was found to have significant associations with mental health. We developed a cross-sectional study with a binomial logistic regression to examine the geriatric depression risk of a high-density city based on five social vulnerability factors and four environmental measures. We constructed a socio-environmental vulnerability index by including the significant variables to map the geriatric depression risk in Hong Kong, a high-density city characterized by compact urban environment and high-rise buildings. Crude and adjusted odds ratios (ORs) of the variables were significantly different, indicating that both social and environmental variables should be included as confounding factors. For the comprehensive model controlled by all confounding factors, older adults who were of lower education had the highest geriatric depression risks (OR: 1.60 (1.21, 2.12)). Higher percentage of residential area and greater variation in building height within the neighborhood also contributed to geriatric depression risk in Hong Kong, while average building height had negative association with geriatric depression risk. In addition, the socio-environmental vulnerability index showed that higher scores were associated with higher geriatric depression risk at neighborhood scale. The results of mapping and cross-section model suggested that geriatric depression risk was associated with a compact living environment with low socio-economic conditions in historical urban areas in Hong Kong. In conclusion, our study found a significant difference in geriatric depression risk between unadjusted and adjusted models, suggesting the importance of including environmental factors in estimating geriatric depression risk. We also developed a framework to map geriatric depression risk across a city, which can be used for identifying neighborhoods with higher risk for public health surveillance and sustainable urban planning. PMID:28858265

[Correlation between body mass index and development of pressure ulcers in intensive care medicine].

PubMed

Catalá Espinosa, A I; Hidalgo Encinas, Y; Cherednichenko, T; Flores Lucas, I; González Tamayo, R; García-Martínez, M Á; Herrero-Gutiérrez, E

2014-01-01

This study aims to evaluate the association between body mass index (BMI), incidence and severity of pressure ulcers (PU) in patients admitted to the Intensive Care Unit (ICU), and describe the differential prognosis of patients with PU and factors that modify it. Case-control study with observation period of 15 months. We collected baseline variables, prognostic scales, therapies and clinical outcome. Univariate analysis was performed for each outcome variable between cases and controls using the appropriate hypothesis test depending on the nature of the variables. ROC curve for BMI and PU. Logistic regression with PU as dependent variable and the covariates that reached p<0.05 in the bivariate analysis. Correlation using Pearson or Spearman was made between BMI, albumin, days to diagnosis of UPP, immobilization, and PU degree. Significance level at p <0.05. 77 patients developed PU and 231 controls were chosen. The cases had higher APACHE II (p=0.043) and SAPS 3 (p=0.023), length of stay in ICU and mechanical ventilation (p<0.001). BMI≥40 was associated with UPP (p=0.024 OR=3.23 CI95% 1.17-8.93). There was a significant association between PU degree, length of stay and MV (p<0,001), but not with immobilization, dynamic support surface and death rate. Multivariate analysis found association between PU, length of MV (p=0.013, OR 1.08, CI95% 1.01-1.16) and kidney replacement therapy (p=0.013, OR 3.55 CI95% 1.31-9.64), with BMI≥40 as a confounding factor. Length of mechanical ventilation and renal replacement therapy are risk factors for pressure ulcer development, and BMI≥40 acts as a confounding factor. PU development and its maximum degree are not associated with a worse prognosis. Copyright © 2013 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

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.

Overlap between autistic and schizotypal personality traits is not accounted for by anxiety and depression.

PubMed

Mealey, Alex; Abbott, Gavin; Byrne, Linda K; McGillivray, Jane

2014-10-30

Autism spectrum and schizophrenia spectrum disorders are classified separately in the DSM-5, yet research indicates that these two disorders share overlapping features. The aim of the present study was to examine the overlap between autistic and schizotypal personality traits and whether anxiety and depression act as confounding variables in this relationship within a non-clinical population. One hundred and forty-four adults completed the Autism Spectrum Quotient and the Schizotypal Personality Questionnaire and the Depression Anxiety Stress Scales-21. A number of associations were seen between autistic and schizotypal personality traits. However, negative traits were the only schizotypal feature to uniquely predict global autistic traits, thus highlighting the importance of interpersonal qualities in the overlap of autistic and schizotypal characteristics. The inclusion of anxiety and depression did not alter relationships between autistic and schizotypal traits, indicating that anxiety and depression are not confounders of this relationship. These findings have important implications for the conceptualisation of both disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Association of Lifestyle-Related Comorbidities With Periodontitis

PubMed Central

Lee, Jae-Hong; Lee, Jung-Seok; Park, Jin-Young; Choi, Jung-Kyu; Kim, Dong-Wook; Kim, Young-Taek; Choi, Seong-Ho

2015-01-01

Abstract The aim of this study was to determine the association of periodontitis with lifestyle-related comorbidities (LCs) using data in the Korean National Health Insurance Cohort Database from 2002 to 2013. This was a retrospective study involving a large national cohort with patient samples (representing 2% of the total Korean population) stratified on the basis of sociodemographic information. Using this precisely extracted database, the correlations between LCs (cerebral infarction, angina pectoris, myocardial infarction, hypertension, diabetes mellitus, rheumatoid arthritis, erectile dysfunction, osteoporosis, and obesity) and periodontitis were investigated while adjusting for confounding bias. Univariate and multiple logistic regression analyses were used to evaluate differences in variable factors. Among a total of 1,025,340 samples, 321,103 (31.3%) cases were diagnosed with periodontitis. Statistically significant associations were found between all LCs except myocardial infarction and periodontitis (P < 0.005). Periodontitis is significantly and positively correlated with LCs (except for myocardial infarction) after adjusting for confounding bias. In particular, lifestyle-related diseases, erectile dysfunction, and osteoporosis seem to be intimately related to periodontitis. PMID:26376407

A pilot study of low-moderate drinking water arsenic contamination and chronic diseases among reproductive age women in Timiş County, Romania.

PubMed

Butts, Celeste D; Bloom, Michael S; Neamtiu, Iulia A; Surdu, Simona; Pop, Cristian; Anastasiu, Doru; Fitzgerald, Edward F; Gurzau, Eugen S

2015-11-01

We conducted a pilot study of associations between drinking water contaminated by inorganic arsenic (iAs), mostly <10 μg/L, and self-reported chronic diseases in 297 pregnant women. Adjusted for confounding variables, we identified a positive association between iAs and heart disease (OR = 1.63, 95%CI 0.81-3.04, p = 0.094), which was stronger for women living at their current residence ≥ 10 years (OR = 2.47, 95%CI 0.87-10.43, p = 0.058). Confounder-adjusted associations were also suggested for iAs with kidney disease (OR = 1.32, 95%CI 0.77-2.21, p = 0.265) and with high blood pressure (OR = 1.36, 95%CI 0.68-2.39, p = 0.300). A post hoc power analysis indicated the need for a larger study with more statistical power. Copyright © 2015 Elsevier B.V. All rights reserved.

Job Search and Social Cognitive Theory: The Role of Career-Relevant Activities

ERIC Educational Resources Information Center

Zikic, Jelena; Saks, Alan M.

2009-01-01

Social cognitive theory was used to explain the relationships between career-relevant activities (environmental and self career exploration, career resources, and training), self-regulatory variables (job search self-efficacy and job search clarity), variables from the Theory of Planned Behavior (job search attitude, subjective norm, job search…

An overview of confounding. Part 2: how to identify it and special situations.

PubMed

Howards, Penelope P

2018-04-01

Confounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time-varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Does extending health insurance coverage to the uninsured improve population health outcomes?

PubMed

Thornton, James A; Rice, Jennifer L

2008-01-01

An ongoing debate exists about whether the US should adopt a universal health insurance programme. Much of the debate has focused on programme implementation and cost, with relatively little attention to benefits for social welfare. To estimate the effect on US population health outcomes, measured by mortality, of extending private health insurance to the uninsured, and to obtain a rough estimate of the aggregate economic benefits of extending insurance coverage to the uninsured. We use state-level panel data for all 50 states for the period 1990-2000 to estimate a health insurance augmented, aggregate health production function for the US. An instrumental variables fixed-effects estimator is used to account for confounding variables and reverse causation from health status to insurance coverage. Several observed factors, such as income, education, unemployment, cigarette and alcohol consumption and population demographic characteristics are included to control for potential confounding variables that vary across both states and time. The results indicate a negative relationship between private insurance and mortality, thus suggesting that extending insurance to the uninsured population would result in an improvement in population health outcomes. The estimate of the marginal effect of insurance coverage indicates that a 10% increase in the population-insured rate of a state reduces mortality by 1.69-1.92%. Using data for the year 2003, we calculate that extending private insurance coverage to the entire uninsured population in the US would save over 75 000 lives annually and may yield annual net benefits to the nation in excess of $US400 billion. This analysis suggests that extending health insurance coverage through the private market to the 46 million Americans without health insurance may well produce large social economic benefits for the nation as a whole.

Kangaroo-mother care method and neurobehavior of preterm infants.

PubMed

Silva, Margareth Gurgel de Castro; Barros, Marina Carvalho de Moraes; Pessoa, Úrsula Maria Lima; Guinsburg, Ruth

2016-04-01

To evaluate the effect of kangaroo-mother care (KMC) in preterm (PT) neurobehavior between 36 and 41 weeks post-conceptual age (PCA). A prospective cohort of 61 preterm infants with gestational age (GA) of 28-32 w evaluated by the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS), with 36-41 w PCA. Infants with clinical instability were excluded. They were analyzed in 2 groups: - Kangaroo (KAN): KMC for 7 or more days; Conventional (CON): did not receive KMC. Scores of the 13 NNNS variables were compared between groups and the effect of KMC in the scores of the variables of NNNS were evaluated by multiple linear regression, controlling for confounders. The KAN groups (n=24) and CON (n=37) were similar regarding main demographic and clinical maternal and neonatal characteristics. Mean GA was 30.3 w; and birth weight was 1170 g for both groups. PT of KAN group were admitted in KMC with PCA of 35.8 w (38.5 days of life) and remained with this care for 14.3 days. The NNNS was applied 13 days after the start of KMC. PT submitted to KMC showed higher quality of movements (KAN: 4.98 ± 0.53 vs CON: 4.53 ± 0.47; p=0.001) and lower scores on Signs of stress and abstinence (KAN: 0.03 ± 0.03 vs CON: 0.05 ± 0.03; p=0.001). Controlling for confounders, the KMC was associated with higher scores on the variables Attention, Quality of movements, and lower scores on Asymmetry and Signs of stress and abstinence. PT submitted to the KMC, compared to those non-submitted, have better neurobehavior performance between 36 and 41 weeks of post-conceptual age. Copyright © 2016. Published by Elsevier Ireland Ltd.

Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin.

PubMed

Biemans, Elke; Hart, Huberta E; Rutten, Guy E H M; Cuellar Renteria, Viviana G; Kooijman-Buiting, Antoinette M J; Beulens, Joline W J

2015-04-01

To investigate the associations of vitamin B12 (cobalamin and holotranscobalamin) status with depression, cognition and neuropathy in patients with type 2 diabetes using metformin. In an observational study, among 550 type 2 diabetes patients using metformin, cobalamin and holotranscobalamin (holoTCII) levels were measured at the annual diabetes checkup, and deficiencies were defined as <148 and <21 pmol/L, respectively. Depression and cognitive function were assessed with corresponding International Classification of Primary Care codes and questionnaires; neuropathy with medical record data and a questionnaire. Confounding variables were retrieved from medical records. Multivariable logistic and linear regressions were used with cobalamin status as independent variable; depression, cognition and neuropathy as dependent variables. The mean duration of diabetes was 8.4 years (±5.8); mean duration of metformin use was 64.1 months (±43.2), with a mean metformin dose of 1,306 mg/day. A sufficient cobalamin level was independently associated with a decreased risk of depression (OR 0.42; 95 % CI 0.23-0.78) and better cognitive performance (β = 1.79; 95 % CI 0.07-3.52) adjusted for confounders. This indicates that cobalamin-deficient patients had a 2.4 times higher chance of depression and a 1.79 point lower cognitive performance score. HoloTCII was not associated with any outcome. Cobalamin deficiency was associated with an increased risk of depression and worse cognitive performance, while holoTCII was not. Screening for cobalamin deficiency may be warranted in diabetes patients using metformin. Physicians should consider a cobalamin deficiency in diabetes patients using metformin with a depression or cognitive decline.

Attendance at cultural events, reading books or periodicals, and making music or singing in a choir as determinants for survival: Swedish interview survey of living conditions.

PubMed Central

Bygren, L. O.; Konlaan, B. B.; Johansson, S. E.

1996-01-01

OBJECTIVES: To investigate the possible influence of attendance at cultural events, reading books or periodicals, making music or singing in a choir as determinants for survival. DESIGN: A simple random sample was drawn of 15,198 individuals aged 16-74 years. Of these, 85% (12,982) were interviewed by trained non-medical interviewers between 1982 and 1983 about cultural activities. They were followed up with respect to survival until 31 December 1991. SETTING: Swedish interview survey of living conditions comprising a random sample of the adult Swedish population. SUBJECTS: 12,675 people interviewed between 1982 and 1983. MAIN OUTCOME MEASURES: Survival of subjects after controlling for eight confounding variables: age, sex, education level, income, long term disease, social network, smoking, and physical exercise. RESULTS: 6,301 men and 6,374 women were followed up; 533 men and 314 women died during this period. The control variables influenced survival in the expected directions except for social network for men; a significant negative effective was found when the analysis was made separately for men and women. We found an influence on mortality when the eight control variables were controlled for in people who rarely attended events compared with those attending most often, the relative risk being 1.57 (95% confidence interval 1.18 to 2.09). CONCLUSION: Attendance at cultural events may have a positive influence on survival. Long term follow up of large samples with confounders that are well controlled for and with the cultural stimulation more highly specified should be used to try to falsify the hypothesis before experiments start. PMID:8990990

Undernutrition as independent predictor of early mortality in elderly cancer patients.

PubMed

Martucci, Renata B; Barbosa, Mariana V; D'Almeida, Cristiane A; Rodrigues, Viviane D; Bergmann, Anke; de Pinho, Nivaldo B; Thuler, Luiz Claudio S

2017-02-01

The aim of this study was to evaluate the 1-y survival of elderly patients with cancer and the association between undernutrition and mortality. This was a cohort study with elderly patients ages ≥65 y admitted between September and October 2014. A nutritionist performed a Mini Nutritional Assessment-Short Form (MNA-SF) assessment during 48 h of hospital admission and collected data about potential confounding variables (comorbidities, stage of cancer, treatment in the previous 3 mo, and reason for hospitalization). Vital status was determined from the medical records or public records office. Overall survival was estimated using the Kaplan-Meier method. Cox regression was performed to estimate unadjusted hazard ratios. Variables with P < 0.20 by univariate analysis were selected for multivariate analysis. P < 0.05 was considered statistically significant. Of the 136 patients (mean age, 73.1 y; 52.2% men), 29.4%, 41.2%, and 29.4% were classified as normal, at risk for undernutrition, and undernutrition, respectively, according to the MNA-SF. The mortality rate was 31.6% after 12 mo. One-year mortality was higher among the undernourished patients, followed by patients at risk for undernutrition. After adjustment for confounding variables, the multivariate regression Cox model showed that being undernourished according to the MNA-SF increased the risk for death at 1 y (hazard ratio, 5.59; 95% confidence interval, 1.8-17.3; P < 0.001). The results showed that the MNA-SF can be a useful tool in identifying elderly patients at higher risk for 1-y mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

An overview of confounding. Part 1: the concept and how to address it.

PubMed

Howards, Penelope P

2018-04-01

Confounding is an important source of bias, but it is often misunderstood. We consider how confounding occurs and how to address confounding using examples. Study results are confounded when the effect of the exposure on the outcome, mixes with the effects of other risk and protective factors for the outcome. This problem arises when these factors are present to different degrees among the exposed and unexposed study participants, but not all differences between the groups result in confounding. Thinking about an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe helps to distinguish confounders from other differences. In an actual study, an observed unexposed population is chosen to stand in for the unobserved parallel universe. Differences between this substitute population and the parallel universe result in confounding. Confounding by identified factors can be addressed analytically and through study design, but only randomization has the potential to address confounding by unmeasured factors. Nevertheless, a given randomized study may still be confounded. Confounded study results can lead to incorrect conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Instrumental variables I: instrumental variables exploit natural variation in nonexperimental data to estimate causal relationships.

PubMed

Rassen, Jeremy A; Brookhart, M Alan; Glynn, Robert J; Mittleman, Murray A; Schneeweiss, Sebastian

2009-12-01

The gold standard of study design for treatment evaluation is widely acknowledged to be the randomized controlled trial (RCT). Trials allow for the estimation of causal effect by randomly assigning participants either to an intervention or comparison group; through the assumption of "exchangeability" between groups, comparing the outcomes will yield an estimate of causal effect. In the many cases where RCTs are impractical or unethical, instrumental variable (IV) analysis offers a nonexperimental alternative based on many of the same principles. IV analysis relies on finding a naturally varying phenomenon, related to treatment but not to outcome except through the effect of treatment itself, and then using this phenomenon as a proxy for the confounded treatment variable. This article demonstrates how IV analysis arises from an analogous but potentially impossible RCT design, and outlines the assumptions necessary for valid estimation. It gives examples of instruments used in clinical epidemiology and concludes with an outline on estimation of effects.

Instrumental variables I: instrumental variables exploit natural variation in nonexperimental data to estimate causal relationships

PubMed Central

Rassen, Jeremy A.; Brookhart, M. Alan; Glynn, Robert J.; Mittleman, Murray A.; Schneeweiss, Sebastian

2010-01-01

The gold standard of study design for treatment evaluation is widely acknowledged to be the randomized controlled trial (RCT). Trials allow for the estimation of causal effect by randomly assigning participants either to an intervention or comparison group; through the assumption of “exchangeability” between groups, comparing the outcomes will yield an estimate of causal effect. In the many cases where RCTs are impractical or unethical, instrumental variable (IV) analysis offers a nonexperimental alternative based on many of the same principles. IV analysis relies on finding a naturally varying phenomenon, related to treatment but not to outcome except through the effect of treatment itself, and then using this phenomenon as a proxy for the confounded treatment variable. This article demonstrates how IV analysis arises from an analogous but potentially impossible RCT design, and outlines the assumptions necessary for valid estimation. It gives examples of instruments used in clinical epidemiology and concludes with an outline on estimation of effects. PMID:19356901

Carbohydrate intake and tennis: are there benefits?

PubMed Central

Kovacs, M S

2006-01-01

Carbohydrate supplementation in prolonged aerobic exercise has been shown to be effective in improving performance and deferring fatigue. However, there is confounding evidence with regard to carbohydrate supplementation and tennis performance, which may be due to the limited number of studies on this topic. This evidence based review, using database searches of Medline and SPORTDiscus, summarises the limited relevant literature to determine if carbohydrate supplementation benefits tennis performance, and, if so, the appropriate amounts and timing. Although more research is required, it appears that it may be beneficial in tennis sessions lasting more than 90 minutes. PMID:16632561

New Metrics for Evaluating Viral Respiratory Pathogenesis

PubMed Central

Menachery, Vineet D.; Gralinski, Lisa E.; Baric, Ralph S.; Ferris, Martin T.

2015-01-01

Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis. PMID:26115403

Dehydration Influences Mood and Cognition: A Plausible Hypothesis?

PubMed Central

Benton, David

2011-01-01

The hypothesis was considered that a low fluid intake disrupts cognition and mood. Most research has been carried out on young fit adults, who typically have exercised, often in heat. The results of these studies are inconsistent, preventing any conclusion. Even if the findings had been consistent, confounding variables such as fatigue and increased temperature make it unwise to extrapolate these findings. Thus in young adults there is little evidence that under normal living conditions dehydration disrupts cognition, although this may simply reflect a lack of relevant evidence. There remains the possibility that particular populations are at high risk of dehydration. It is known that renal function declines in many older individuals and thirst mechanisms become less effective. Although there are a few reports that more dehydrated older adults perform cognitive tasks less well, the body of information is limited and there have been little attempt to improve functioning by increasing hydration status. Although children are another potentially vulnerable group that have also been subject to little study, they are the group that has produced the only consistent findings in this area. Four intervention studies have found improved performance in children aged 7 to 9 years. In these studies children, eating and drinking as normal, have been tested on occasions when they have and not have consumed a drink. After a drink both memory and attention have been found to be improved. PMID:22254111

The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: A systematic review

PubMed Central

Prina, A. Matthew; Cosco, Theodore D.; Dening, Tom; Beekman, Aartjan; Brayne, Carol; Huisman, Martijn

2015-01-01

Objectives This paper aims to systematically review observational studies that have analysed whether depressive symptoms in the community are associated with higher general hospital admissions, longer hospital stays and increased risk of re-admission. Methods We identified prospective studies that looked at depressive symptoms in the community as a risk factor for non-psychiatric general hospital admissions, length of stay or risk of re-admission. The search was carried out on MEDLINE, PsycINFO, Cochrane Library Database, and followed up with contact with authors and scanning of reference lists. Results Eleven studies fulfilled our inclusion and exclusion criteria, and all were deemed to be of moderate to high quality. Meta-analysis of seven studies with relevant data suggested that depressive symptoms may be a predictor of subsequent admission to a general hospital in unadjusted analyses (RR = 1.36, 95% CI: 1.28–1.44), but findings after adjustment for confounding variables were inconsistent. The narrative synthesis also reported depressive symptoms to be independently associated with longer length of stay, and higher re-admission risk. Conclusions Depressive symptoms are associated with a higher risk of hospitalisation, longer length of stay and a higher re-admission risk. Some of these associations may be mediated by other factors, and should be explored in more details. PMID:25466985

[Assessment of risk of death due to malignant neoplasms induced by occupational exposure in a rubber footwear plant].

PubMed

Szymczak, Wiesław; Sobala, Wojciech; Wilczyńska, Urszula; Szeszenia-Dabrowska, Neonila

2003-01-01

The main goal of the study was to analyze thoroughly the results of a cohort study. Such an analysis renders it possible to eliminate certain neoplasms as those not related to the observed exposure. The cohort study was carried out in a group of workers, covering 11,342 persons (5472 men and 5870 women), employed for at least one year during the years 1945-1985 in a rubber footwear plant. The cohort study was continued until the end of December 1997. Of all the sites of malignant neoplasms observed in the cohort, significant, exposure-related excess mortality was found to be due to malignant neoplasms of larynx and lung in men, and malignant neoplasms of gallbladder and lung in women. For these neoplasms, the values of observed risk among those exposed were significantly higher than among non-exposed. Moreover, in a certain interval of employment duration, an increase in risk rates with increasing duration of employment under exposure was observed, which suggests the presence of dose-response relationship. For all these sites, a relevant trend was shown by the RR values calculated in relation to the group of persons non-exposed but employed in the same plant. The internal reference group used to calculate RR values allowed to eliminate the effect of confounding variables, which is not always possible when the general population is used as the reference group.

An analysis of the impact of pre‐analytical factors on the urine proteome: Sample processing time, temperature, and proteolysis

PubMed Central

Hepburn, Sophie; Cairns, David A.; Jackson, David; Craven, Rachel A.; Riley, Beverley; Hutchinson, Michelle; Wood, Steven; Smith, Matthew Welberry; Thompson, Douglas

2015-01-01

Purpose We have examined the impact of sample processing time delay, temperature, and the addition of protease inhibitors (PIs) on the urinary proteome and peptidome, an important aspect of biomarker studies. Experimental design Ten urine samples from patients with varying pathologies were each divided and PIs added to one‐half, with aliquots of each then processed and frozen immediately, or after a delay of 6 h at 4°C or room temperature (20–22°C), effectively yielding 60 samples in total. Samples were then analyzed by 2D‐PAGE, SELDI‐TOF‐MS, and immunoassay. Results Interindividual variability in profiles was the dominant feature in all analyses. Minimal changes were observed by 2D‐PAGE as a result of delay in processing, temperature, or PIs and no changes were seen in IgG, albumin, β2‐microglobulin, or α1‐microglobulin measured by immunoassay. Analysis of peptides showed clustering of some samples by presence/absence of PIs but the extent was very patient‐dependent with most samples showing minimal effects. Conclusions and clinical relevance The extent of processing‐induced changes and the benefit of PI addition are patient‐ and sample‐dependent. A consistent processing methodology is essential within a study to avoid any confounding of the results. PMID:25400092

Marital status and optimism score among breast cancer survivors.

PubMed

Croft, Lindsay; Sorkin, John; Gallicchio, Lisa

2014-11-01

There are an increasing number of breast cancer survivors, but their psychosocial and supportive care needs are not well-understood. Recent work has found marital status, social support, and optimism to be associated with quality of life, but little research has been conducted to understand how these factors relate to one another. Survey data from 722 breast cancer survivors were analyzed to estimate the association between marital status and optimism score, as measured using the Life Orientation Test-Revised. Linear regression was used to estimate the relationship of marital status and optimism, controlling for potential confounding variables and assessing effect modification. The results showed that the association between marital status and optimism was modified by time since breast cancer diagnosis. Specifically, in those most recently diagnosed (within 5 years), married breast cancer survivors had a 1.50 higher mean optimism score than unmarried survivors (95 % confidence interval (CI) 0.37, 2.62; p = 0.009). The difference in optimism score by marital status was not present more than 5 years from breast cancer diagnosis. Findings suggest that among breast cancer survivors within 5 years since diagnosis, those who are married have higher optimism scores than their unmarried counterparts; this association was not observed among longer-term breast cancer survivors. Future research should examine whether the difference in optimism score among this subgroup of breast cancer survivors is clinically relevant.

Dehydration influences mood and cognition: a plausible hypothesis?

PubMed

Benton, David

2011-05-01

The hypothesis was considered that a low fluid intake disrupts cognition and mood. Most research has been carried out on young fit adults, who typically have exercised, often in heat. The results of these studies are inconsistent, preventing any conclusion. Even if the findings had been consistent, confounding variables such as fatigue and increased temperature make it unwise to extrapolate these findings. Thus in young adults there is little evidence that under normal living conditions dehydration disrupts cognition, although this may simply reflect a lack of relevant evidence. There remains the possibility that particular populations are at high risk of dehydration. It is known that renal function declines in many older individuals and thirst mechanisms become less effective. Although there are a few reports that more dehydrated older adults perform cognitive tasks less well, the body of information is limited and there have been little attempt to improve functioning by increasing hydration status. Although children are another potentially vulnerable group that have also been subject to little study, they are the group that has produced the only consistent findings in this area. Four intervention studies have found improved performance in children aged 7 to 9 years. In these studies children, eating and drinking as normal, have been tested on occasions when they have and not have consumed a drink. After a drink both memory and attention have been found to be improved.