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.

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.

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.

Confounding adjustment in comparative effectiveness research conducted within distributed research networks.

PubMed

Toh, Sengwee; Gagne, Joshua J; Rassen, Jeremy A; Fireman, Bruce H; Kulldorff, Martin; Brown, Jeffrey S

2013-08-01

A distributed research network (DRN) of electronic health care databases, in which data reside behind the firewall of each data partner, can support a wide range of comparative effectiveness research (CER) activities. An essential component of a fully functional DRN is the capability to perform robust statistical analyses to produce valid, actionable evidence without compromising patient privacy, data security, or proprietary interests. We describe the strengths and limitations of different confounding adjustment approaches that can be considered in observational CER studies conducted within DRNs, and the theoretical and practical issues to consider when selecting among them in various study settings. Several methods can be used to adjust for multiple confounders simultaneously, either as individual covariates or as confounder summary scores (eg, propensity scores and disease risk scores), including: (1) centralized analysis of patient-level data, (2) case-centered logistic regression of risk set data, (3) stratified or matched analysis of aggregated data, (4) distributed regression analysis, and (5) meta-analysis of site-specific effect estimates. These methods require different granularities of information be shared across sites and afford investigators different levels of analytic flexibility. DRNs are growing in use and sharing of highly detailed patient-level information is not always feasible in DRNs. Methods that incorporate confounder summary scores allow investigators to adjust for a large number of confounding factors without the need to transfer potentially identifiable information in DRNs. They have the potential to let investigators perform many analyses traditionally conducted through a centralized dataset with detailed patient-level information.

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

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.

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

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

Efficient and accurate causal inference with hidden confounders from genome-transcriptome variation data

PubMed Central

2017-01-01

Mapping gene expression as a quantitative trait using whole genome-sequencing and transcriptome analysis allows to discover the functional consequences of genetic variation. We developed a novel method and ultra-fast software Findr for higly accurate causal inference between gene expression traits using cis-regulatory DNA variations as causal anchors, which improves current methods by taking into consideration hidden confounders and weak regulations. Findr outperformed existing methods on the DREAM5 Systems Genetics challenge and on the prediction of microRNA and transcription factor targets in human lymphoblastoid cells, while being nearly a million times faster. Findr is publicly available at https://github.com/lingfeiwang/findr. PMID:28821014

Hospital ownership and financial performance: what explains the different findings in the empirical literature?

PubMed

Shen, Yu-Chu; Eggleston, Karen; Lau, Joseph; Schmid, Christopher H

2007-01-01

This study applies meta-analytic methods to conduct a quantitative review of the empirical literature on hospital ownership since 1990. We examine four financial outcomes across 40 studies: cost, revenue, profit margin, and efficiency. We find that variation in the magnitudes of ownership effects can be explained by a study's research focus and methodology. Studies using empirical methods that control for few confounding factors tend to find larger differences between for-profit and not-for-profit hospitals than studies that control for a wider range of confounding factors. Functional form and sample size also matter. Failure to apply log transformation to highly skewed expenditure data yields misleadingly large estimated differences between for-profits and not-for-profits. Studies with fewer than 200 observations also produce larger point estimates and wide confidence intervals.

Concentrations of Water-Soluble Vitamins in Blood and Urinary Excretion in Patients with Diabetes Mellitus.

PubMed

Iwakawa, Hiromi; Nakamura, Yasuyuki; Fukui, Tomiho; Fukuwatari, Tsutomu; Ugi, Satoshi; Maegawa, Hiroshi; Doi, Yukio; Shibata, Katsumi

2016-01-01

We examined the concentrations of water-soluble vitamins in blood and urinary excretion of 22 patients with type 2 diabetes mellitus (type 2DM) and 20 healthy control participants. Macronutrient and vitamin intakes of type 2DM subjects were measured using a weighed food record method. Control participants consumed a semipurified diet for eight days. Multiple linear regression models were used to determine whether significant differences existed in vitamin concentrations in blood independent of age, sex, and other confounding factors. Concentrations of vitamins B2, B6, C, niacin, and folate in blood were significantly lower in type 2DM subjects than in controls, independent of confounding factors. Renal clearances of vitamins B6, C, niacin, and folate were significantly higher in type 2DM subjects than in controls. In conclusion, concentrations of vitamins B2, B6, C, niacin, and folate in blood were significantly lower in type 2DM subjects than in controls, independent of confounding factors; based on the evidence of increased urinary clearance of these vitamins, the lower levels were likely due to impaired reabsorption processes.

Sick-building symptoms in office workers in northeastern France: a pilot study.

PubMed

Teculescu, D B; Sauleau, E A; Massin, N; Bohadana, A B; Buhler, O; Benamghar, L; Mur, J M

1998-07-01

To verify that sick building symptoms are present in north-eastern France office workers; to try to identify new confounding factors. The design was that of a cross-sectional study with control group. We studied with the same methods the personnel of an air-conditioned building (n=425), and of a naturally ventilated building (n=351). Air temperature and humidity, bacterial and fungal densities were measured by the same technical staff in the two buildings. A standard questionnaire on irritative and respiratory symptoms, personal and family history, and lifestyle was completed by the participants. In univariate analysis, exposure to air-conditioning was associated with an increased prevalence of symptoms (odds ratios-OR-between 1.54 and 2.84). A significant increase in sickness absence was also found among subjects working in air-conditioned offices. As a series of factors were suspected to interfere with these associations, logistic regression was applied. This method confirmed exposure to be an independent determinant of 7 symptoms, and also identified two determinants not previously described: a family history of respiratory diseases and "do-it-yourself' activities. we found the sick building symptoms to be present in a group of French office workers exposed to air-conditioning. We confirmed the influence of a number of confounding factors and described two further confounders - do-it-yourself activities at home and a history of familial respiratory disease.

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

PubMed

Woolgar, Alexandra; Golland, Polina; Bode, Stefan

2014-09-01

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

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.

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

PubMed Central

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

2010-01-01

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

When can the cause of a population decline be determined?

PubMed

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

2016-11-01

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

When can the cause of a population decline be determined?

USGS Publications Warehouse

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

2016-01-01

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

Offspring ADHD as a Risk Factor for Parental Marital Problems: Controls for Genetic and Environmental Confounds

PubMed Central

Schermerhorn, Alice C.; D’Onofrio, Brian M.; Slutske, Wendy S.; Emery, Robert E.; Turkheimer, Eric; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

2013-01-01

Background Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. The reasons for this association are unclear, however. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method Data were drawn from the Australian Twin Registry, including 1296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Results Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems. PMID:22958575

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

Investigation of Chemical Exchange at Intermediate Exchange Rates using a Combination of Chemical Exchange Saturation Transfer (CEST) and Spin-Locking methods (CESTrho)

PubMed Central

Kogan, Feliks; Singh, Anup; Cai, Keija; Haris, Mohammad; Hariharan, Hari; Reddy, Ravinder

2011-01-01

Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. In this study we developed a new method to measure proton exchange which combines chemical exchange saturation transfer (CEST) and T1ρ magnetization preparation methods (CESTrho). We demonstrated that this new CESTrho sequence can detect proton exchange in the slow to intermediate exchange regimes. It has a linear dependence on proton concentration which allows it to be used to quantitatively measure changes in metabolite concentration. Additionally, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate while retaining its dependency on solute concentration. Finally, we showed the feasibility of using CESTrho in vivo. This sequence is able to detect proton exchange at intermediate exchange rates and is unaffected by the confounding factors that influence proton exchange rates thus making it ideal for the measurement of metabolites with exchangeable protons in this exchange regime. PMID:22009759

Investigation of chemical exchange at intermediate exchange rates using a combination of chemical exchange saturation transfer (CEST) and spin-locking methods (CESTrho).

PubMed

Kogan, Feliks; Singh, Anup; Cai, Keija; Haris, Mohammad; Hariharan, Hari; Reddy, Ravinder

2012-07-01

Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. In this study we developed a new method to measure proton exchange which combines chemical exchange saturation transfer and T(1)(ρ) magnetization preparation methods (CESTrho). We demonstrated that this new CESTrho sequence can detect proton exchange in the slow to intermediate exchange regimes. It has a linear dependence on proton concentration which allows it to be used to quantitatively measure changes in metabolite concentration. Additionally, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate while retaining its dependency on solute concentration. Finally, we showed the feasibility of using CESTrho in vivo. This sequence is able to detect proton exchange at intermediate exchange rates and is unaffected by the confounding factors that influence proton exchange rates thus making it ideal for the measurement of metabolites with exchangeable protons in this exchange regime. Copyright © 2011 Wiley Periodicals, Inc.

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.

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.

Self-efficacy difference among patients with cancer with different socioeconomic status: application of latent class analysis and standardization and decomposition analysis.

PubMed

Yuan, Changrong; Wei, Chunlan; Wang, Jichuan; Qian, Huijuan; Ye, Xianghong; Liu, Yingyan; Hinds, Pamela S

2014-06-01

Although the relationship between partial socioeconomic status (SES) and self-efficacy has been studied in previous studies, few research have examined self-efficacy difference among patients with cancer with different SES. A cross-sectional survey involving 764 patients with cancer was completed. Latent class analysis (LCA) was applied to identify distinct groups of patients with cancer using four SES indicators (education, income, employment status and health insurance status). Standardization and decomposition analysis (SDA) was then used to examine differences in patients' self-efficacy among SES groups and the components of the differences attributed to confounding factors, such as gender, age, anxiety, depression and social support. Participants were classified into four distinctive SES groups via using LCA method, and the observed self-efficacy level significantly varied by SES groups; as theorized, higher self-efficacy was associated with higher SES. The self-efficacy differences by SES groups were decomposed into "real" group differences and factor component effects that are attributed to group differences in confounding factor compositions. Self-efficacy significantly varies by SES. Social support significantly confounded the observed differences in self-efficacy between different SES groups among Chinese patients with cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroticism explains unwanted variance in Implicit Association Tests of personality: possible evidence for an affective valence confound.

PubMed

Fleischhauer, Monika; Enge, Sören; Miller, Robert; Strobel, Alexander; Strobel, Anja

2013-01-01

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

Supervised normalization of microarrays

PubMed Central

Mecham, Brigham H.; Nelson, Peter S.; Storey, John D.

2010-01-01

Motivation: A major challenge in utilizing microarray technologies to measure nucleic acid abundances is ‘normalization’, the goal of which is to separate biologically meaningful signal from other confounding sources of signal, often due to unavoidable technical factors. It is intuitively clear that true biological signal and confounding factors need to be simultaneously considered when performing normalization. However, the most popular normalization approaches do not utilize what is known about the study, both in terms of the biological variables of interest and the known technical factors in the study, such as batch or array processing date. Results: We show here that failing to include all study-specific biological and technical variables when performing normalization leads to biased downstream analyses. We propose a general normalization framework that fits a study-specific model employing every known variable that is relevant to the expression study. The proposed method is generally applicable to the full range of existing probe designs, as well as to both single-channel and dual-channel arrays. We show through real and simulated examples that the method has favorable operating characteristics in comparison to some of the most highly used normalization methods. Availability: An R package called snm implementing the methodology will be made available from Bioconductor (http://bioconductor.org). Contact: jstorey@princeton.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20363728

Statistical primer: propensity score matching and its alternatives.

PubMed

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

2018-06-01

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

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.

Assessment Intelligence in Small Group Learning

ERIC Educational Resources Information Center

Xing, Wanli; Wu, Yonghe

2014-01-01

Assessment of groups in CSCL context is a challenging task fraught with many confounding factors collected and measured. Previous documented studies are by and large summative in nature and some process-oriented methods require time-intensive coding of qualitative data. This study attempts to resolve these problems for teachers to assess groups…

Selecting Evaluation Comparison Groups: A Cluster Analytic Approach.

ERIC Educational Resources Information Center

Davis, Todd Mclin; McLean, James E.

A persistent problem in the evaluation of field-based projects is the lack of no-treatment comparison groups. Frequently, potential comparison groups are confounded by socioeconomic, racial, or other factors. Among the possible methods for dealing with this problem are various matching procedures, but they are cumbersome to use with multiple…

Hierarchical analysis of forest bird species-environment relationships in the Oregon Coast Range

Treesearch

Samuel A. Cushman; Kevin McGarigal

2004-01-01

Species in biological communities respond to environmental variation simultaneously across a range of organizational levels. Accordingly, it is important to quantify the effects of environmental factors at multiple levels on species distribution and abundance. Hierarchical methods that explicitly separate the independent and confounded influences of environmental...

Examining the Intergenerational Transmission of Violence in a New Zealand Birth Cohort

ERIC Educational Resources Information Center

Fergusson, David M.; Boden, Joseph M.; Horwood, L. John

2006-01-01

Objective: This paper examines whether exposure to interparental violence in childhood predicts subsequent involvement in interpartner violence and violent crime after controlling for potentially confounding factors. Method: The investigation analyses data from the Christchurch Health and Development Study, a prospective, longitudinal study of a…

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

PubMed

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

2011-03-01

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

Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT

NASA Astrophysics Data System (ADS)

Maspero, Matteo; Seevinck, Peter R.; Schubert, Gerald; Hoesl, Michaela A. U.; van Asselen, Bram; Viergever, Max A.; Lagendijk, Jan J. W.; Meijer, Gert J.; van den Berg, Cornelis A. T.

2017-02-01

Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in the prostate. This study will be valuable for institutions interested in introducing MR-only dose planning in their clinical practice.

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

PubMed Central

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

2013-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

USDA-ARS?s Scientific Manuscript database

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

The Relationship between Frequency of Family Dinner and Adolescent Problem Behaviors after Adjusting for Other Family Characteristics

ERIC Educational Resources Information Center

Sen, Bisakha

2010-01-01

Objective: To examine the association between frequency of family dinners (FFD) and selected problem behaviors for adolescents after adjusting for family connectedness, parental awareness, other family activities, and other potentially confounding factors. Methods: Data are drawn from the National Longitudinal Survey of Youth, 1997. The primary…

An operant-based detection method for inferring tinnitus in mice.

PubMed

Zuo, Hongyan; Lei, Debin; Sivaramakrishnan, Shobhana; Howie, Benjamin; Mulvany, Jessica; Bao, Jianxin

2017-11-01

Subjective tinnitus is a hearing disorder in which a person perceives sound when no external sound is present. It can be acute or chronic. Because our current understanding of its pathology is incomplete, no effective cures have yet been established. Mouse models are useful for studying the pathophysiology of tinnitus as well as for developing therapeutic treatments. We have developed a new method for determining acute and chronic tinnitus in mice, called sound-based avoidance detection (SBAD). The SBAD method utilizes one paradigm to detect tinnitus and another paradigm to monitor possible confounding factors, such as motor impairment, loss of motivation, and deficits in learning and memory. The SBAD method has succeeded in monitoring both acute and chronic tinnitus in mice. Its detection ability is further validated by functional studies demonstrating an abnormal increase in neuronal activity in the inferior colliculus of mice that had previously been identified as having tinnitus by the SBAD method. The SBAD method provides a new means by which investigators can detect tinnitus in a single mouse accurately and with more control over potential confounding factors than existing methods. This work establishes a new behavioral method for detecting tinnitus in mice. The detection outcome is consistent with functional validation. One key advantage of mouse models is they provide researchers the opportunity to utilize an extensive array of genetic tools. This new method could lead to a deeper understanding of the molecular pathways underlying tinnitus pathology. Copyright © 2017 Elsevier B.V. All rights reserved.

Limitations of a metabolic network-based reverse ecology method for inferring host-pathogen interactions.

PubMed

Takemoto, Kazuhiro; Aie, Kazuki

2017-05-25

Host-pathogen interactions are important in a wide range of research fields. Given the importance of metabolic crosstalk between hosts and pathogens, a metabolic network-based reverse ecology method was proposed to infer these interactions. However, the validity of this method remains unclear because of the various explanations presented and the influence of potentially confounding factors that have thus far been neglected. We re-evaluated the importance of the reverse ecology method for evaluating host-pathogen interactions while statistically controlling for confounding effects using oxygen requirement, genome, metabolic network, and phylogeny data. Our data analyses showed that host-pathogen interactions were more strongly influenced by genome size, primary network parameters (e.g., number of edges), oxygen requirement, and phylogeny than the reserve ecology-based measures. These results indicate the limitations of the reverse ecology method; however, they do not discount the importance of adopting reverse ecology approaches altogether. Rather, we highlight the need for developing more suitable methods for inferring host-pathogen interactions and conducting more careful examinations of the relationships between metabolic networks and host-pathogen interactions.

A prospective cohort study of disability pension due to mental diagnoses: the importance of health factors and behaviors

PubMed Central

2013-01-01

Background Previous studies have found associations between various health factors and behaviors and mental disorders. However, knowledge of such associations with disability pension (DP) due to mental diagnoses is scarce. Moreover, the influence of familial factors (genetics and family background) on the associations are mainly unknown. The aim of the study was to investigate associations between health factors and behaviors and future DP due to mental diagnoses in a twin cohort, accounting for familial confounding. Methods A prospective cohort study of Swedish twins (N=28 613), including survey data and national register data on DP and other background factors was conducted. Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for the whole twin cohort, and for discordant twin pairs. Results During follow-up 1998–2008 (median 10 years), 2.2% of the cohort was granted a DP with a mental diagnosis. In the fully adjusted analyses of the whole cohort, the associations of poor or moderate self-rated health (SRH), under- or overweight, former or current tobacco use, or being an abstainer from alcohol were significantly associated with risk of DP due to mental diagnoses. Analyses of discordant twin pairs confirmed all these associations, except for current tobacco use, being independent from familial confounding. Exclusion of individuals with current or previous depression or anxiety at baseline did not influence the associations found. Conclusions Poor or moderate SRH, under- or overweight, former tobacco use or being an abstainer from alcohol seem to be strong direct predictors of DP due to mental diagnoses, independently of several confounders of this study, including familial factors. PMID:23816331

Developing hazelnut tissue culture medium free of ion confounding

USDA-ARS?s Scientific Manuscript database

The general approach for tissue culture medium optimization is to use salts as factors in experimental design and analysis. However, using salts as factors leads to ion confounding, making it difficult to detect the effects of individual ions on particular growth responses. This study focused on tes...

LD Score Regression Distinguishes Confounding from Polygenicity in Genome-Wide Association Studies

PubMed Central

Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary; Ripke, Stephan; Yang, Jian; Patterson, Nick; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.

2015-01-01

Both polygenicity (i.e., many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of test statistic inflation in many GWAS of large sample size. PMID:25642630

Human Health and Exposure to Electromagnetic Radiation

DTIC Science & Technology

1992-07-01

electromagnetic field exposures and cancer. Studies of electrical and electronic workers are suggestive of such a link, but are subject to the confounding factor ...associations between cancer and electrical installations 108 51 Factors associated with increased risk of childhood cancer in the Denver studies 109 52...It is important in epidemiological studies to make Arenuous efforts to adjust for possible confounding factors , many - in particular the early

Effectiveness and confounding factors of penetrating astigmatic keratotomy in clinical practice

PubMed Central

Yen, Chu-Yu; Tseng, Gow-Lieng

2018-01-01

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

Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score.

PubMed

Sugihara, Masahiro

2010-01-01

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log-rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan-Meier estimators of survival curves using an IPTW log-rank test for multi-valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. (c) 2009 John Wiley & Sons, Ltd.

Trimodel Mammography with Perfect Coregistration

DTIC Science & Technology

2017-02-01

background, the major confounding factor in reading mammography; the imaging characteristics suggest that this contrast mechanism would be preferable...image with enhanced edges and reduced anatomical background, the major confounding factor in reading mammography; the imaging characteristics suggest...subjects, vertebrate animals , biohazards, and/or select agents Describe significant deviations, unexpected outcomes, or changes in approved protocols

Language Outcomes at 12 Years for Children Exposed Prenatally to Cocaine

ERIC Educational Resources Information Center

Lewis, Barbara A.; Minnes, Sonia; Short, Elizabeth J.; Min, Meeyoung O.; Wu, Miaoping; Lang, Adelaide; Weishampel, Paul; Singer, Lynn T.

2013-01-01

Purpose: In this study, the authors aimed to examine the long-term effects of prenatal cocaine exposure (PCE) on the language development of 12-year-old children using a prospective design, controlling for confounding prenatal drug exposure and environmental factors. Method: Children who were exposed to cocaine in utero (PCE; "n" = 183)…

Not All Lexical Access Tasks Are Created Equal: Lexical Development between Three and Five

ERIC Educational Resources Information Center

Isacoff, Nora M.; Stromswold, Karin

2014-01-01

Lexical access tasks are designed to measure efficiency of lexical access, but task demands and methods vary greatly. Many lexical access tasks do not account for confounding factors including competence in other linguistic abilities. In this study, preschoolers were given two lexical access tasks. In the single-category naming (SCN) task,…

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.

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.

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.

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

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.

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

Older men with higher self-rated socioeconomic status have shorter telomeres

PubMed Central

Woo, Jean; Suen, Eddie W. C.; Leung, Jason C. S.; Tang, Nelson L. S.; Ebrahim, Shah

2009-01-01

Background: previous studies examining the relationship between socioeconomic status and telomere length showed conflicting results, one study finding shorter telomere length in subjects with lower socioeconomic status and one showing no relationship. Design: cross-sectional study. Setting: community-living elderly Chinese in Hong Kong. Objective: this study examines the relationship between self-rated social economic status and telomere length in Hong Kong Chinese men and women aged 65 years and over living in the community. Subjects and method: information was collected from 958 men and 978 women regarding possible confounding factors such as the presence of chronic diseases, smoking, physical activity level, dietary intake and body mass index. Telomere length was measured by quantitative PCR. Result: in men only, after adjustment for age and other confounding factors, a higher ranking in community standing was associated with shorter telomere length. Conclusion: men with higher self-rated socioeconomic status have shorter telomeres, possibly mediated through psychosocial rather than lifestyle factors or the presence of chronic disease. There may be cultural ethnic and age-related differences in social determinants of health. PMID:19556325

Relationship between Socioeconomic Status and Physical Fitness in Junior High School Students

ERIC Educational Resources Information Center

Bohr, Adam D.; Brown, Dale D.; Laurson, Kelly R.; Smith, Peter J. K.; Bass, Ronald W.

2013-01-01

Background: Research on physical fitness often regards socioeconomic status (SES) as a confounding factor. However, few studies investigate the impact of SES on fitness. This study investigated the impact of SES on physical fitness in both males and females, with an economic-based construct of SES. Methods: The sample consisted of 954 6th, 7th,…

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.

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.

Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach

PubMed Central

Gao, Shuyang; Ver Steeg, Greg; Galstyan, Aram

2015-01-01

We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect—length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors. PMID:26115446

Is the Association of Subjective SES and Self-Rated Health Confounded by Negative Mood? An Experimental Approach

PubMed Central

Kraus, Michael W.; Adler, Nancy; David Chen, Teh-Way

2012-01-01

Objective Lower subjective socioeconomic status (SSS) consistently shows associations with poorer health with the strongest relationships emerging with global self-rated health. Though often interpreted as reflecting the impact of low SSS on health, the association could also arise from confounding SSS with negative affect. In this research we sought to determine if negative affect confounds, or alternatively, is on the causal pathway linking SSS to self-rated health. Methods 300 adult participants—recruited from throughout the United States—were randomized to experience sadness, shame, or a neutral mood induction wherein they wrote about and visualized a particularly emotionally evocative event. Participants subsequently completed measures of SSS, self-rated health, depression, and negative mood. Results Consistent with predictions, neither SSS scores nor the association of SSS with self-rated health, depression, and chronic negative affect differed by mood induction condition, controlling for demographic factors that covary with SSS (e.g., age, gender, education, income). Moreover, chronic negative affect partially explained the relationship between SSS and self-rated health, independent of manipulated mood. Conclusions These findings support the utility of the measurement of SSS, and provide evidence suggesting that chronic negative affect is a likely mediator of the SSS association with global health rather than a confounder. PMID:22329426

Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison

PubMed Central

Class, Quetzal A.; Rickert, Martin E.; Larsson, Henrik; Lichtenstein, Paul; D’Onofrio, Brian M.

2014-01-01

Background It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. Aims To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. Method We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. Results In the population, lower birth weight (⩽2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Conclusions Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems. PMID:25257067

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

ERIC Educational Resources Information Center

Lee, Paul H.

2017-01-01

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

Causal Methods for Observational Research: A Primer.

PubMed

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

2018-04-01

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

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.

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.

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

PubMed

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

2013-02-01

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

The art of matching brain tissue from patients and controls for postmortem research.

PubMed

Bao, Ai-Min; Swaab, Dick F

2018-01-01

The quality of postmortem research depends strongly on a thorough clinical investigation and documentation of the patient's disorder and therapies. In addition, a systematic and professional neuropathologic investigation of both cases and controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of clinical neurologic diagnoses, despite being made in first-rate clinics, have to be revised or require an extra diagnosis after a complete and thorough review by the NBB. The neuropathology examination may reveal for instance that the "controls" already have preclinical neurodegenerative alterations. In postmortem studies the patient and control groups must be matched for as many of the known confounding factors as possible. This is necessary to make the groups as similar as possible, except for the topic being investigated. Confounding factors are present before, during, and after death. They are respectively: (1) genetic background, systemic diseases, duration and gravity of illness, medicines and addictive compounds used, age, sex, gender identity, sexual orientation, circadian and seasonal fluctuations, lateralization; (2) agonal state, stress of dying; and (3) postmortem delay, freezing procedures, fixation and storage time. Consequently, a brain bank should have a large number of controls at its disposal for appropriate matching. If matching fails for some confounders, then their influence may be determined by statistical methods such as analysis of variance or regression models. Copyright © 2018 Elsevier B.V. All rights reserved.

Survey material choices in haematology EQA: a confounding factor in automated counting performance assessment.

PubMed

De la Salle, Barbara

2017-02-15

The complete blood count (CBC) is one of the most frequently requested tests in laboratory medicine, performed in a range of healthcare situations. The provision of an ideal assay material for external quality assessment is confounded by the fragility of the cellular components of blood, the lack of commutability of stabilised whole blood material and the lack of certified reference materials and methods to which CBC results can be traced. The choice of assay material between fresh blood, extended life assay material and fully stabilised, commercially prepared, whole blood material depends upon the scope and objectives of the EQA scheme. The introduction of new technologies in blood counting and the wider clinical application of parameters from the extended CBC will bring additional challenges for the EQA provider.

Commentary: How can family-based quasi-experimental designs and national registers be used to address confounding in risk factor studies of psychopathology? A reflection on Obel et al. (2016).

PubMed

Larsson, Henrik

2016-04-01

Standard observational studies have reported a robust correlation between maternal smoking during pregnancy and risk of ADHD in offspring. In the accompanying article, Obel et al. used sibling-comparisons to explore the extent to which unmeasured familial confounding explains this association. This commentary highlights three important implications of the study. At a general level, Obel et al. illustrates how (1) family-based quasi-experimental designs and (2) national registers can be used to address confounding in risk factor studies of psychopathology. At a more specific level, the study suggests that maternal smoking during pregnancy is probably not a causal risk factor for ADHD. © 2016 Association for Child and Adolescent Mental Health.

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

PubMed Central

Källén, Bengt

2012-01-01

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

Changes in Landscape Greenness and Climatic Factors over ...

EPA Pesticide Factsheets

Monitoring and quantifying changes in vegetation cover over large areas using remote sensing can be achieved using the Normalized Difference Vegetation Index (NDVI), an indicator of greenness. However, distinguishing gradual shifts in NDVI (e.g. climate change) versus direct and rapid changes (e.g., fire, land development) is challenging as changes can be confounded by time-dependent patterns, and variation associated with climatic factors. In the present study we leveraged a method, that we previously developed for a pilot study, to address these confounding factors by evaluating NDVI change using autoregression techniques that compare results from univariate (NDVI vs. time) and multivariate analyses (NDVI vs. time and climatic factors) for ~7,660,636 1-km2 pixels comprising the 48 contiguous states of the USA, over a 25-year period (1989−2013). NDVI changed significantly for 48% of the nation over the 25-year in the univariate analyses where most significant trends (85%) indicated an increase in greenness over time. By including climatic factors in the multivariate analyses of NDVI over time, the detection of significant NDVI trends increased to 53% (an increase of 5%). Comparisons of univariate and multivariate analyses for each pixel showed that less than 4% of the pixels had a significant NDVI trend attributable to gradual climatic changes while the remainder of pixels with a significant NDVI trend indicated that changes were due to direct factors. Whi

Confounding in statistical mediation analysis: What it is and how to address it.

PubMed

Valente, Matthew J; Pelham, William E; Smyth, Heather; MacKinnon, David P

2017-11-01

Psychology researchers are often interested in mechanisms underlying how randomized interventions affect outcomes such as substance use and mental health. Mediation analysis is a common statistical method for investigating psychological mechanisms that has benefited from exciting new methodological improvements over the last 2 decades. One of the most important new developments is methodology for estimating causal mediated effects using the potential outcomes framework for causal inference. Potential outcomes-based methods developed in epidemiology and statistics have important implications for understanding psychological mechanisms. We aim to provide a concise introduction to and illustration of these new methods and emphasize the importance of confounder adjustment. First, we review the traditional regression approach for estimating mediated effects. Second, we describe the potential outcomes framework. Third, we define what a confounder is and how the presence of a confounder can provide misleading evidence regarding mechanisms of interventions. Fourth, we describe experimental designs that can help rule out confounder bias. Fifth, we describe new statistical approaches to adjust for measured confounders of the mediator-outcome relation and sensitivity analyses to probe effects of unmeasured confounders on the mediated effect. All approaches are illustrated with application to a real counseling intervention dataset. Counseling psychologists interested in understanding the causal mechanisms of their interventions can benefit from incorporating the most up-to-date techniques into their mediation analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed Central

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

2015-01-01

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

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

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

PubMed Central

Perin, Jamie; Walker, Neff

2015-01-01

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

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

PubMed

Perin, Jamie; Walker, Neff

2015-01-01

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

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.

Phenotypic variation as an indicator of pesticide stress in gudgeon: Accounting for confounding factors in the wild.

PubMed

Shinn, Cândida; Blanchet, Simon; Loot, Géraldine; Lek, Sovan; Grenouillet, Gaël

2015-12-15

The response of organisms to environmental stress is currently used in the assessment of ecosystem health. Morphological changes integrate the multiple effects of one or several stress factors upon the development of the exposed organisms. In a natural environment, many factors determine the patterns of morphological differentiation between individuals. However, few studies have sought to distinguish and measure the independent effect of these factors (genetic diversity and structure, spatial structuring of populations, physical-chemical conditions, etc.). Here we investigated the relationship between pesticide levels measured at 11 sites sampled in rivers of the Garonne river basin (SW France) and morphological changes of a freshwater fish species, the gudgeon (Gobio gobio). Each individual sampled was genotyped using 8 microsatellite markers and their phenotype characterized via 17 morphological traits. Our analysis detected a link between population genetic structure (revealed by a Bayesian method) and morphometry (linear discriminant analysis) of the studied populations. We then developed an original method based on general linear models using distance matrices, an extension of the partial Mantel test beyond 3 matrices. This method was used to test the relationship between contamination (toxicity index) and morphometry (PST of morphometric traits), taking into account (1) genetic differentiation between populations (FST), (2) geographical distances between sites, (3) site catchment area, and (4) various physical-chemical parameters for each sampling site. Upon removal of confounding effects, 3 of the 17 morphological traits studied were significantly correlated with pesticide toxicity, suggesting a response of these traits to the anthropogenic stress. These results underline the importance of taking into account the different sources of phenotypic variability between organisms when identifying the stress factors involved. The separation and quantification of the independent effect of such factors provides an interesting outlook regarding the use of these evaluation metrics as indicators of ecosystem health. Copyright © 2015 Elsevier B.V. All rights reserved.

Leveraging Hierarchical Population Structure in Discrete Association Studies

PubMed Central

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

2007-01-01

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

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

PubMed

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

2013-10-01

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

Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

PubMed

Asimakopoulou, K G; Hampson, S E; Morrish, N J

2002-04-01

Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

Association Between Cardiovascular Risk Factors and Carpal Tunnel Syndrome in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew Steven; Kapellusch, Jay; Merryweather, Andrew S; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Wertsch, Jacqueline; Foster, James; Garg, Arun; Drury, David L

2016-01-01

The aim of the study was to ascertain if cardiovascular (CVD) risk factors are carpal tunnel syndrome (CTS) risk factors. Analysis of pooled baseline data from two large prospective cohort studies (n = 1824) assessed the relationships between a modified Framingham Heart Study CVD risk score both CTS and abnormal nerve conduction study prevalence. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratio and 95% confidence intervals were calculated for individual risk scores. There was a strong relationship between CVD risk score and both CTS and abnormal nerve conduction study after adjustment for confounders, with odds ratios as high as 4.16 and 7.35, respectively. Dose responses were also observed. In this workplace population, there is a strong association between CVD risk scores and both CTS and abnormal nerve conduction study that persisted after controlling for confounders. These data suggest a potentially modifiable disease mechanism.

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

PubMed

Wagner, Louis K

2014-10-01

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

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

PubMed Central

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

Effectively identifying regulatory hotspots while capturing expression heterogeneity in gene expression studies

PubMed Central

2014-01-01

Expression quantitative trait loci (eQTL) mapping is a tool that can systematically identify genetic variation affecting gene expression. eQTL mapping studies have shown that certain genomic locations, referred to as regulatory hotspots, may affect the expression levels of many genes. Recently, studies have shown that various confounding factors may induce spurious regulatory hotspots. Here, we introduce a novel statistical method that effectively eliminates spurious hotspots while retaining genuine hotspots. Applied to simulated and real datasets, we validate that our method achieves greater sensitivity while retaining low false discovery rates compared to previous methods. PMID:24708878

Does Regular Online Testing Enhance Student Learning in the Numerical Sciences? Robust Evidence from a Large Data Set

ERIC Educational Resources Information Center

Angus, Simon D.; Watson, Judith

2009-01-01

While a number of studies have been conducted on the impact of online assessment and teaching methods on student learning, the field does not seem settled around the promised benefits of such approaches. It is argued that the reason for this state of affairs is that few studies have been able to control for a number of confounding factors in…

Controlling Response Shift Bias: The Use of the Retrospective Pre-Test Design in the Evaluation of a Master's Programme

ERIC Educational Resources Information Center

Drennan, Jonathan; Hyde, Abbey

2008-01-01

Traditionally the measures used to evaluate the impact of an educational programme on student outcomes and the extent to which students change is a comparison of the student's pre-test scores with his/her post-test scores. However, this method of evaluating change may be problematic due to the confounding factor of response shift bias when student…

Neighborhood Contributions to Racial and Ethnic Disparities in Obesity Among New York City Adults.

PubMed

Lim, Sungwoo; Harris, Tiffany G

2015-01-01

Objectives. We assessed neighborhood confounding on racial/ethnic obesity disparities among adults in New York City after accounting for complex sampling, and how much neighborhood factors (walkability, percentage Black or Hispanic, poverty) contributed to this effect. Methods. We combined New York City Community Health Survey 2002-2004 data with Census 2000 zip code-level data. We estimated odds ratios (ORs) for obesity with 2 sets of regression analyses. First, we used the method incorporating the conditional pseudolikelihood into complex sample adjustment. Second, we compared ORs for race/ethnicity from a conventional multilevel model for each neighborhood factor with those from a hybrid fixed-effect model. Results. The weighted estimate for obesity for Blacks versus Whites (OR = 1.8; 95% confidence interval = 1.6, 2.0) was attenuated when we controlled neighborhood confounding (OR = 1.4; 95% confidence interval = 1.2, 1.6; first analysis). Percentage of Blacks in the neighborhood made a large contribution whereas the walkability contribution was minimal (second analysis). Conclusions. Percentage of Blacks in New York City neighborhoods explained a large portion of the disparity in obesity between Blacks and Whites. The study highlights the importance of estimating valid neighborhood effects for public health surveillance and intervention.

MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample

PubMed Central

2012-01-01

Background Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. Methods We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. Results When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. Conclusions The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease. PMID:23116433

On the Confounding Effect of Temperature on Chemical Shift-Encoded Fat Quantification

PubMed Central

Hernando, Diego; Sharma, Samir D.; Kramer, Harald; Reeder, Scott B.

2014-01-01

Purpose To characterize the confounding effect of temperature on chemical shift-encoded (CSE) fat quantification. Methods The proton resonance frequency of water, unlike triglycerides, depends on temperature. This leads to a temperature dependence of the spectral models of fat (relative to water) that are commonly used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat–water signals at various temperatures and echo time combinations. Oil–water phantoms were constructed and scanned at temperatures between 0 and 40°C using spectroscopy and CSE imaging at three echo time combinations. An explanted human liver, rejected for transplantation due to steatosis, was scanned using spectroscopy and CSE imaging. Fat–water reconstructions were performed using four different techniques: magnitude and complex fitting, with standard or temperature-corrected signal modeling. Results In all experiments, magnitude fitting with standard signal modeling resulted in large fat quantification errors. Errors were largest for echo time combinations near TEinit ≈ 1.3 ms, ΔTE ≈ 2.2 ms. Errors in fat quantification caused by temperature-related frequency shifts were smaller with complex fitting, and were avoided using a temperature-corrected signal model. Conclusion Temperature is a confounding factor for fat quantification. If not accounted for, it can result in large errors in fat quantifications in phantom and ex vivo acquisitions. PMID:24123362

Paternal and maternal alcohol abuse and offspring mental distress in the general population: the Nord-Trøndelag health study

PubMed Central

2012-01-01

Background The degree to which parental alcohol abuse is a risk factor for offspring mental distress is unclear, due to conflicting results of previous research. The inconsistencies in previous findings may be related to sample characteristics and lack of control of confounding or moderating factors. One such factor may be the gender of the abusing parent. Also, other factors, such as parental mental health, divorce, adolescent social network, school functioning or self-esteem, may impact the outcome. This study examines the impact of maternal and paternal alcohol abuse on adolescent mental distress, including potentially confounding, mediating or moderating effects of various variables. Methods Data from the Nord-Trøndelag Health Study (HUNT), a Norwegian population based health survey, from 4012 offspring and their parents were analyzed. Parental alcohol abuse was measured by numerical consumption indicators and CAGE, whereas offspring mental distress was measured by SCL-5, an abbreviated instrument tapping symptoms of anxiety and depression. Statistical method was analysis of variance. Results Maternal alcohol abuse was related to offspring mental distress, whereas no effect could be shown of paternal alcohol abuse. Effects of maternal alcohol abuse was partly mediated by parental mental distress, offspring social network and school functioning. However, all effects were relatively small. Conclusions The results indicate graver consequences for offspring of alcohol abusing mothers compared to offspring of alcohol abusing fathers. However, small effect sizes suggest that adolescent offspring of alcohol abusing parents in general manage quite well. PMID:22708789

Clinical and evoked pain, personality traits, and emotional states: can familial confounding explain the associations?

PubMed

Strachan, Eric; Poeschla, Brian; Dansie, Elizabeth; Succop, Annemarie; Chopko, Laura; Afari, Niloofar

2015-01-01

Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample. 99 female twin pairs were evaluated for clinical and evoked pain using the McGill Pain Questionnaire (MPQ) and dolorimetry, and completed the 120-item International Personality Item Pool (IPIP), the Positive and Negative Affect Scale (PANAS), and ratings of stress and mood. Using a co-twin control design we examined a) the relationship of personality traits and emotional states with clinical and evoked pain and b) whether genetics and common environment (i.e. familial factors) may account for the associations. Neuroticism was associated with the sensory component of the MPQ; this relationship was not confounded by familial factors. None of the emotional state measures was associated with the MPQ. PANAS negative affect was associated with lower evoked pressure pain threshold and tolerance; these associations were confounded by familial factors. There were no associations between IPIP traits and evoked pain. A relationship exists between neuroticism and clinical pain that is not confounded by familial factors. There is no similar relationship between negative emotional states and clinical pain. In contrast, the relationship between negative emotional states and evoked pain is strong while the relationship with enduring personality traits is weak. The relationship between negative emotional states and evoked pain appears to be non-causal and due to familial factors. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Assessing Hospital Performance After Percutaneous Coronary Intervention Using Big Data.

PubMed

Spertus, Jacob V; T Normand, Sharon-Lise; Wolf, Robert; Cioffi, Matt; Lovett, Ann; Rose, Sherri

2016-11-01

Although risk adjustment remains a cornerstone for comparing outcomes across hospitals, optimal strategies continue to evolve in the presence of many confounders. We compared conventional regression-based model to approaches particularly suited to leveraging big data. We assessed hospital all-cause 30-day excess mortality risk among 8952 adults undergoing percutaneous coronary intervention between October 1, 2011, and September 30, 2012, in 24 Massachusetts hospitals using clinical registry data linked with billing data. We compared conventional logistic regression models with augmented inverse probability weighted estimators and targeted maximum likelihood estimators to generate more efficient and unbiased estimates of hospital effects. We also compared a clinically informed and a machine-learning approach to confounder selection, using elastic net penalized regression in the latter case. Hospital excess risk estimates range from -1.4% to 2.0% across methods and confounder sets. Some hospitals were consistently classified as low or as high excess mortality outliers; others changed classification depending on the method and confounder set used. Switching from the clinically selected list of 11 confounders to a full set of 225 confounders increased the estimation uncertainty by an average of 62% across methods as measured by confidence interval length. Agreement among methods ranged from fair, with a κ statistic of 0.39 (SE: 0.16), to perfect, with a κ of 1 (SE: 0.0). Modern causal inference techniques should be more frequently adopted to leverage big data while minimizing bias in hospital performance assessments. © 2016 American Heart Association, Inc.

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

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.

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

USDA-ARS?s Scientific Manuscript database

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

Risk Factors in Adolescent Hypertension

PubMed Central

Ewald, D. Rose; Haldeman, Lauren A.

2016-01-01

Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

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

PubMed

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

2014-08-27

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

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.

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

PubMed

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

2017-07-19

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

Effects of Sample Preparation on the Infrared Reflectance Spectra of Powders

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

Brauer, Carolyn S.; Johnson, Timothy J.; Myers, Tanya L.

2015-05-22

While reflectance spectroscopy is a useful tool in identifying molecular compounds, laboratory measurement of solid (particularly powder) samples often is confounded by sample preparation methods. For example, both the packing density and surface roughness can have an effect on the quantitative reflectance spectra of powdered samples. Recent efforts in our group have focused on developing standard methods for measuring reflectance spectra that accounts for sample preparation, as well as other factors such as particle size and provenance. In this work, the effect of preparation method on sample reflectivity was investigated by measuring the directional-hemispherical spectra of samples that were hand-packedmore » as well as pressed into pellets using an integrating sphere attached to a Fourier transform infrared spectrometer. The results show that the methods used to prepare the sample have a substantial effect on the measured reflectance spectra, as do other factors such as particle size.« less

Effects of sample preparation on the infrared reflectance spectra of powders

NASA Astrophysics Data System (ADS)

Brauer, Carolyn S.; Johnson, Timothy J.; Myers, Tanya L.; Su, Yin-Fong; Blake, Thomas A.; Forland, Brenda M.

2015-05-01

While reflectance spectroscopy is a useful tool for identifying molecular compounds, laboratory measurement of solid (particularly powder) samples often is confounded by sample preparation methods. For example, both the packing density and surface roughness can have an effect on the quantitative reflectance spectra of powdered samples. Recent efforts in our group have focused on developing standard methods for measuring reflectance spectra that accounts for sample preparation, as well as other factors such as particle size and provenance. In this work, the effect of preparation method on sample reflectivity was investigated by measuring the directional-hemispherical spectra of samples that were hand-loaded as well as pressed into pellets using an integrating sphere attached to a Fourier transform infrared spectrometer. The results show that the methods used to prepare the sample can have a substantial effect on the measured reflectance spectra, as do other factors such as particle size.

Isolated and synergistic effects of PM10 and average temperature on cardiovascular and respiratory mortality.

PubMed

Pinheiro, Samya de Lara Lins de Araujo; Saldiva, Paulo Hilário Nascimento; Schwartz, Joel; Zanobetti, Antonella

2014-12-01

OBJECTIVE To analyze the effect of air pollution and temperature on mortality due to cardiovascular and respiratory diseases. METHODS We evaluated the isolated and synergistic effects of temperature and particulate matter with aerodynamic diameter < 10 µm (PM10) on the mortality of individuals > 40 years old due to cardiovascular disease and that of individuals > 60 years old due to respiratory diseases in Sao Paulo, SP, Southeastern Brazil, between 1998 and 2008. Three methodologies were used to evaluate the isolated association: time-series analysis using Poisson regression model, bidirectional case-crossover analysis matched by period, and case-crossover analysis matched by the confounding factor, i.e., average temperature or pollutant concentration. The graphical representation of the response surface, generated by the interaction term between these factors added to the Poisson regression model, was interpreted to evaluate the synergistic effect of the risk factors. RESULTS No differences were observed between the results of the case-crossover and time-series analyses. The percentage change in the relative risk of cardiovascular and respiratory mortality was 0.85% (0.45;1.25) and 1.60% (0.74;2.46), respectively, due to an increase of 10 μg/m3 in the PM10 concentration. The pattern of correlation of the temperature with cardiovascular mortality was U-shaped and that with respiratory mortality was J-shaped, indicating an increased relative risk at high temperatures. The values for the interaction term indicated a higher relative risk for cardiovascular and respiratory mortalities at low temperatures and high temperatures, respectively, when the pollution levels reached approximately 60 μg/m3. CONCLUSIONS The positive association standardized in the Poisson regression model for pollutant concentration is not confounded by temperature, and the effect of temperature is not confounded by the pollutant levels in the time-series analysis. The simultaneous exposure to different levels of environmental factors can create synergistic effects that are as disturbing as those caused by extreme concentrations.

Socioeconomic Factors and Women's Use of Complementary and Alternative Medicine in Four Racial/Ethnic Groups

PubMed Central

Chao, Maria T.; Wade, Christine M.

2014-01-01

Objective Higher socioeconomic status (SES) is associated with using complementary and alternative medicine (CAM) in national surveys. Less is known about how socioeconomic factors affect CAM use in US subpopulations. We examined whether the relationship between SES and CAM use differs by racial/ethnic groups. Methods Using national survey data, we assessed education and income effects on women's CAM use in four racial/ethnic groups (Whites, Blacks, Mexican Americans, and Chinese Americans), controlling for age, health status, and geographic region. CAM use was defined as using any of 11 domains in the prior year. Results Adjusted effects of SES on CAM use were similar among Mexican American and non-Hispanic White women—education had a distinct gradient effect, with each increasing level of education significantly more likely to use CAM; household income ≥$60,000 was associated with CAM use compared to income <$20,000. For Chinese American women, socioeconomic factors were not associated with CAM use when controlling for confounders. Although income was not associated with CAM use among African American women, college graduates were three times more likely to use CAM than those with less than a high school education, adjusting for confounders. Conclusion SES effects on CAM use are not uniform across racial/ethnic populations. Other factors, such as culture and social networks, may interact with SES to influence CAM use in minority populations. PMID:18447102

Rumination, anxiety, depressive symptoms and subsequent depression in adolescents at risk for psychopathology: a longitudinal cohort study

PubMed Central

2013-01-01

Background A ruminative style of responding to low mood is associated with subsequent high depressive symptoms and depressive disorder in children, adolescents and adults. Scores on self-report rumination scales correlate strongly with scores on anxiety and depression symptom scales. This may confound any associations between rumination and subsequent depression. Methods Our sample comprised 658 healthy adolescents at elevated risk for psychopathology. This study applied ordinal item (non-linear) factor analysis to pooled items from three self-report questionnaires to explore whether there were separate, but correlated, constructs of rumination, depression and anxiety. It then tested whether rumination independently predicted depressive disorder and depressive symptoms over the subsequent 12 months, after adjusting for confounding variables. Results We identified a single rumination factor, which was correlated with factors representing cognitive symptoms of depression, somatic symptoms of depression and anxiety symptoms; and one factor representing adaptive responses to low mood. Elevated rumination scores predicted onset of depressive disorders over the subsequent year (p = 0.035), and levels of depressive symptoms 12 months later (p < 0.0005), after adjustment for prior levels of depressive and anxiety symptoms. Conclusion High rumination predicts onset of depressive disorder in healthy adolescents. Therapy that reduces rumination and increases distraction/problem-solving may reduce onset and relapse rates of depression. PMID:24103296

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

ERIC Educational Resources Information Center

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

2018-01-01

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

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

PubMed Central

2017-01-01

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

Associations Between Divorce and Onset of Drug Abuse in a Swedish National Sample.

PubMed

Edwards, Alexis C; Larsson Lönn, Sara; Sundquist, Jan; Kendler, Kenneth S; Sundquist, Kristina

2018-05-01

Rates of drug abuse are higher among divorced individuals than among those who are married, but it is not clear whether divorce itself is a risk factor for drug abuse or whether the observed association is confounded by other factors. We examined the association between divorce and onset of drug abuse in a population-based Swedish cohort born during 1965-1975 (n = 651,092) using Cox proportional hazards methods, with marital status as a time-varying covariate. Potential confounders (e.g., demographics, adolescent deviance, and family history of drug abuse) were included as covariates. Parallel analyses were conducted for widowhood and drug-abuse onset. In models with adjustments, divorce was associated with a substantial increase in risk of drug-abuse onset in both sexes (hazard ratios > 5). Co-relative analyses (among biological relatives) were consistent with a partially causal role of divorce on drug-abuse onset. Widowhood also increased risk of drug-abuse onset, although to a lesser extent. Divorce is a potent risk factor for onset of drug abuse, even after adjusting for deviant behavior in adolescence and family history of drug abuse. The somewhat less-pronounced association with widowhood, particularly among men, suggests that the magnitude of association between divorce and drug abuse may not be generalizable to the end of a relationship.

Inverse Association between Fruit and Vegetable Intake and BMI even after Controlling for Demographic, Socioeconomic and Lifestyle Factors

PubMed Central

Heo, Moonseong; Kim, Ryung S.; Wylie-Rosett, Judith; Allison, David B.; Heymsfield, Steve B.; Faith, Myles S.

2011-01-01

Objective To estimate fruit and vegetable (FV) intake levels of US adult population and evaluate the association between FV intake and BMI status after controlling for confounding demographic, socioeconomic and lifestyle factors. We also sought to identify moderating factors. Methods We used 2007 Behavior Risk Factors Surveillance System (N > 400,000) data. FV intake was dichotomized as ≥5 servings (FV5+) versus <5 servings/day. BMI status was categorized as normal, overweight, and obese. Identification of moderators was performed by testing interactions between BMI status and other variables using bivariate analyses followed by multiple logistic regression analysis incorporating complex survey sampling design features. Results Only 24.6% of US adults consumed ≥5 servings per day and less than 4% consumed 9 or more servings. Overweight (% FV5+ = 23.9%) and obese (21.9%) groups consumed significantly less FV than the normal-weight (27.4%) group (p < 0.0001). This inverse association remained significant even after controlling for potential confounding factors. Multivariate analysis identified five significant moderators (p < 0.0001) after controlling for all evaluated variables: race, sex, smoking status, health coverage, and physical activity. Notably, physically inactive obese males tended to consume the least FV (% FV5+ = 14.7%). Conclusion Current US population FV intake level is below recommended levels. The inverse association between FV intake and obesity was significant and was moderated by demographic, socioeconomic status, and lifestyle factors. These factors should be considered when developing policies and interventions to increase FV intake. PMID:22248995

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

Propensity score to detect baseline imbalance in cluster randomized trials: the role of the c-statistic.

PubMed

Leyrat, Clémence; Caille, Agnès; Foucher, Yohann; Giraudeau, Bruno

2016-01-22

Despite randomization, baseline imbalance and confounding bias may occur in cluster randomized trials (CRTs). Covariate imbalance may jeopardize the validity of statistical inferences if they occur on prognostic factors. Thus, the diagnosis of a such imbalance is essential to adjust statistical analysis if required. We developed a tool based on the c-statistic of the propensity score (PS) model to detect global baseline covariate imbalance in CRTs and assess the risk of confounding bias. We performed a simulation study to assess the performance of the proposed tool and applied this method to analyze the data from 2 published CRTs. The proposed method had good performance for large sample sizes (n =500 per arm) and when the number of unbalanced covariates was not too small as compared with the total number of baseline covariates (≥40% of unbalanced covariates). We also provide a strategy for pre selection of the covariates needed to be included in the PS model to enhance imbalance detection. The proposed tool could be useful in deciding whether covariate adjustment is required before performing statistical analyses of CRTs.

On the equivalence of case-crossover and time series methods in environmental epidemiology.

PubMed

Lu, Yun; Zeger, Scott L

2007-04-01

The case-crossover design was introduced in epidemiology 15 years ago as a method for studying the effects of a risk factor on a health event using only cases. The idea is to compare a case's exposure immediately prior to or during the case-defining event with that same person's exposure at otherwise similar "reference" times. An alternative approach to the analysis of daily exposure and case-only data is time series analysis. Here, log-linear regression models express the expected total number of events on each day as a function of the exposure level and potential confounding variables. In time series analyses of air pollution, smooth functions of time and weather are the main confounders. Time series and case-crossover methods are often viewed as competing methods. In this paper, we show that case-crossover using conditional logistic regression is a special case of time series analysis when there is a common exposure such as in air pollution studies. This equivalence provides computational convenience for case-crossover analyses and a better understanding of time series models. Time series log-linear regression accounts for overdispersion of the Poisson variance, while case-crossover analyses typically do not. This equivalence also permits model checking for case-crossover data using standard log-linear model diagnostics.

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.

Evaluating the impact of implementation factors on family-based prevention programming: methods for strengthening causal inference.

PubMed

Crowley, D Max; Coffman, Donna L; Feinberg, Mark E; Greenberg, Mark T; Spoth, Richard L

2014-04-01

Despite growing recognition of the important role implementation plays in successful prevention efforts, relatively little work has sought to demonstrate a causal relationship between implementation factors and participant outcomes. In turn, failure to explore the implementation-to-outcome link limits our understanding of the mechanisms essential to successful programming. This gap is partially due to the inability of current methodological procedures within prevention science to account for the multitude of confounders responsible for variation in implementation factors (i.e., selection bias). The current paper illustrates how propensity and marginal structural models can be used to improve causal inferences involving implementation factors not easily randomized (e.g., participant attendance). We first present analytic steps for simultaneously evaluating the impact of multiple implementation factors on prevention program outcome. Then, we demonstrate this approach for evaluating the impact of enrollment and attendance in a family program, over and above the impact of a school-based program, within PROSPER, a large-scale real-world prevention trial. Findings illustrate the capacity of this approach to successfully account for confounders that influence enrollment and attendance, thereby more accurately representing true causal relations. For instance, after accounting for selection bias, we observed a 5% reduction in the prevalence of 11th grade underage drinking for those who chose to receive a family program and school program compared to those who received only the school program. Further, we detected a 7% reduction in underage drinking for those with high attendance in the family program.

Bias, Confounding, and Interaction: Lions and Tigers, and Bears, Oh My!

PubMed

Vetter, Thomas R; Mascha, Edward J

2017-09-01

Epidemiologists seek to make a valid inference about the causal effect between an exposure and a disease in a specific population, using representative sample data from a specific population. Clinical researchers likewise seek to make a valid inference about the association between an intervention and outcome(s) in a specific population, based upon their randomly collected, representative sample data. Both do so by using the available data about the sample variable to make a valid estimate about its corresponding or underlying, but unknown population parameter. Random error in an experiment can be due to the natural, periodic fluctuation or variation in the accuracy or precision of virtually any data sampling technique or health measurement tool or scale. In a clinical research study, random error can be due to not only innate human variability but also purely chance. Systematic error in an experiment arises from an innate flaw in the data sampling technique or measurement instrument. In the clinical research setting, systematic error is more commonly referred to as systematic bias. The most commonly encountered types of bias in anesthesia, perioperative, critical care, and pain medicine research include recall bias, observational bias (Hawthorne effect), attrition bias, misclassification or informational bias, and selection bias. A confounding variable is a factor associated with both the exposure of interest and the outcome of interest. A confounding variable (confounding factor or confounder) is a variable that correlates (positively or negatively) with both the exposure and outcome. Confounding is typically not an issue in a randomized trial because the randomized groups are sufficiently balanced on all potential confounding variables, both observed and nonobserved. However, confounding can be a major problem with any observational (nonrandomized) study. Ignoring confounding in an observational study will often result in a "distorted" or incorrect estimate of the association or treatment effect. Interaction among variables, also known as effect modification, exists when the effect of 1 explanatory variable on the outcome depends on the particular level or value of another explanatory variable. Bias and confounding are common potential explanations for statistically significant associations between exposure and outcome when the true relationship is noncausal. Understanding interactions is vital to proper interpretation of treatment effects. These complex concepts should be consistently and appropriately considered whenever one is not only designing but also analyzing and interpreting data from a randomized trial or observational study.

The crowding factor method applied to parafoveal vision

PubMed Central

Ghahghaei, Saeideh; Walker, Laura

2016-01-01

Crowding increases with eccentricity and is most readily observed in the periphery. During natural, active vision, however, central vision plays an important role. Measures of critical distance to estimate crowding are difficult in central vision, as these distances are small. Any overlap of flankers with the target may create an overlay masking confound. The crowding factor method avoids this issue by simultaneously modulating target size and flanker distance and using a ratio to compare crowded to uncrowded conditions. This method was developed and applied in the periphery (Petrov & Meleshkevich, 2011b). In this work, we apply the method to characterize crowding in parafoveal vision (<3.5 visual degrees) with spatial uncertainty. We find that eccentricity and hemifield have less impact on crowding than in the periphery, yet radial/tangential asymmetries are clearly preserved. There are considerable idiosyncratic differences observed between participants. The crowding factor method provides a powerful tool for examining crowding in central and peripheral vision, which will be useful in future studies that seek to understand visual processing under natural, active viewing conditions. PMID:27690170

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

PubMed Central

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

2016-01-01

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

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.

Educational gains in cause-specific mortality: Accounting for cognitive ability and family-level confounders using propensity score weighting.

PubMed

Bijwaard, Govert E; Myrskylä, Mikko; Tynelius, Per; Rasmussen, Finn

2017-07-01

A negative educational gradient has been found for many causes of death. This association may be partly explained by confounding factors that affect both educational attainment and mortality. We correct the cause-specific educational gradient for observed individual background and unobserved family factors using an innovative method based on months lost due to a specific cause of death re-weighted by the probability of attaining a higher educational level. We use data on men with brothers from the Swedish Military Conscription Registry (1951-1983), linked to administrative registers. This dataset of some 700,000 men allows us to distinguish between five education levels and many causes of death. The empirical results reveal that raising the educational level from primary to tertiary would result in an additional 20 months of survival between ages 18 and 63. This improvement in mortality is mainly attributable to fewer deaths from external causes. The highly educated gain more than nine months due to the reduction in deaths from external causes, but gain only two months due to the reduction in cancer mortality and four months due to the reduction in cardiovascular mortality. Ignoring confounding would lead to an underestimation of the gains by educational attainment, especially for the less educated. Our results imply that if the education distribution of 50,000 Swedish men from the 1951 cohort were replaced with that of the corresponding 1983 cohort, 22% of the person-years that were lost to death between ages 18 and 63 would have been saved for this cohort. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of confounding variables on hemodynamic response function estimation using averaging and deconvolution analysis: An event-related NIRS study.

PubMed

Aarabi, Ardalan; Osharina, Victoria; Wallois, Fabrice

2017-07-15

Slow and rapid event-related designs are used in fMRI and functional near-infrared spectroscopy (fNIRS) experiments to temporally characterize the brain hemodynamic response to discrete events. Conventional averaging (CA) and the deconvolution method (DM) are the two techniques commonly used to estimate the Hemodynamic Response Function (HRF) profile in event-related designs. In this study, we conducted a series of simulations using synthetic and real NIRS data to examine the effect of the main confounding factors, including event sequence timing parameters, different types of noise, signal-to-noise ratio (SNR), temporal autocorrelation and temporal filtering on the performance of these techniques in slow and rapid event-related designs. We also compared systematic errors in the estimates of the fitted HRF amplitude, latency and duration for both techniques. We further compared the performance of deconvolution methods based on Finite Impulse Response (FIR) basis functions and gamma basis sets. Our results demonstrate that DM was much less sensitive to confounding factors than CA. Event timing was the main parameter largely affecting the accuracy of CA. In slow event-related designs, deconvolution methods provided similar results to those obtained by CA. In rapid event-related designs, our results showed that DM outperformed CA for all SNR, especially above -5 dB regardless of the event sequence timing and the dynamics of background NIRS activity. Our results also show that periodic low-frequency systemic hemodynamic fluctuations as well as phase-locked noise can markedly obscure hemodynamic evoked responses. Temporal autocorrelation also affected the performance of both techniques by inducing distortions in the time profile of the estimated hemodynamic response with inflated t-statistics, especially at low SNRs. We also found that high-pass temporal filtering could substantially affect the performance of both techniques by removing the low-frequency components of HRF profiles. Our results emphasize the importance of characterization of event timing, background noise and SNR when estimating HRF profiles using CA and DM in event-related designs. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

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.

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

PubMed Central

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

2012-01-01

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

Detecting and correcting the bias of unmeasured factors using perturbation analysis: a data-mining approach.

PubMed

Lee, Wen-Chung

2014-02-05

The randomized controlled study is the gold-standard research method in biomedicine. In contrast, the validity of a (nonrandomized) observational study is often questioned because of unknown/unmeasured factors, which may have confounding and/or effect-modifying potential. In this paper, the author proposes a perturbation test to detect the bias of unmeasured factors and a perturbation adjustment to correct for such bias. The proposed method circumvents the problem of measuring unknowns by collecting the perturbations of unmeasured factors instead. Specifically, a perturbation is a variable that is readily available (or can be measured easily) and is potentially associated, though perhaps only very weakly, with unmeasured factors. The author conducted extensive computer simulations to provide a proof of concept. Computer simulations show that, as the number of perturbation variables increases from data mining, the power of the perturbation test increased progressively, up to nearly 100%. In addition, after the perturbation adjustment, the bias decreased progressively, down to nearly 0%. The data-mining perturbation analysis described here is recommended for use in detecting and correcting the bias of unmeasured factors in observational studies.

Meta-analysis of lung cancer in asphalt roofing and paving workers with external adjustment for confounding by coal tar

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

Fayerweather, W.E.

2007-07-01

The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. The meta-Relative Risk (meta-RR) and its variance were estimatedmore » by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chi-square and I{sup 2} tests. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.« less

Relative preservation of the recognition of positive facial expression "happiness" in Alzheimer disease.

PubMed

Maki, Yohko; Yoshida, Hiroshi; Yamaguchi, Tomoharu; Yamaguchi, Haruyasu

2013-01-01

Positivity recognition bias has been reported for facial expression as well as memory and visual stimuli in aged individuals, whereas emotional facial recognition in Alzheimer disease (AD) patients is controversial, with possible involvement of confounding factors such as deficits in spatial processing of non-emotional facial features and in verbal processing to express emotions. Thus, we examined whether recognition of positive facial expressions was preserved in AD patients, by adapting a new method that eliminated the influences of these confounding factors. Sensitivity of six basic facial expressions (happiness, sadness, surprise, anger, disgust, and fear) was evaluated in 12 outpatients with mild AD, 17 aged normal controls (ANC), and 25 young normal controls (YNC). To eliminate the factors related to non-emotional facial features, averaged faces were prepared as stimuli. To eliminate the factors related to verbal processing, the participants were required to match the images of stimulus and answer, avoiding the use of verbal labels. In recognition of happiness, there was no difference in sensitivity between YNC and ANC, and between ANC and AD patients. AD patients were less sensitive than ANC in recognition of sadness, surprise, and anger. ANC were less sensitive than YNC in recognition of surprise, anger, and disgust. Within the AD patient group, sensitivity of happiness was significantly higher than those of the other five expressions. In AD patient, recognition of happiness was relatively preserved; recognition of happiness was most sensitive and was preserved against the influences of age and disease.

The intergenerational transmission of conduct problems.

PubMed

Raudino, Alessandra; Fergusson, David M; Woodward, Lianne J; Horwood, L John

2013-03-01

Drawing on prospective longitudinal data, this paper examines the intergenerational transmission of childhood conduct problems in a sample of 209 parents and their 331 biological offspring studied as part of the Christchurch Health and Developmental Study. The aims were to estimate the association between parental and offspring conduct problems and to examine the extent to which this association could be explained by (a) confounding social/family factors from the parent's childhood and (b) intervening factors reflecting parental behaviours and family functioning. The same item set was used to assess childhood conduct problems in parents and offspring. Two approaches to data analysis (generalised estimating equation regression methods and latent variable structural equation modelling) were used to examine possible explanations of the intergenerational continuity in behaviour. Regression analysis suggested that there was moderate intergenerational continuity (r = 0.23, p < 0.001) between parental and offspring conduct problems. This continuity was not explained by confounding factors but was partially mediated by parenting behaviours, particularly parental over-reactivity. Latent variable modelling designed to take account of non-observed common genetic and environmental factors underlying the continuities in problem behaviours across generations also suggested that parenting behaviour played a role in mediating the intergenerational transmission of conduct problems. There is clear evidence of intergenerational continuity in conduct problems. In part this association reflects a causal chain process in which parental conduct problems are associated (directly or indirectly) with impaired parenting behaviours that in turn influence risks of conduct problems in offspring.

Logistic Regression Likelihood Ratio Test Analysis for Detecting Signals of Adverse Events in Post-market Safety Surveillance.

PubMed

Nam, Kijoeng; Henderson, Nicholas C; Rohan, Patricia; Woo, Emily Jane; Russek-Cohen, Estelle

2017-01-01

The Vaccine Adverse Event Reporting System (VAERS) and other product surveillance systems compile reports of product-associated adverse events (AEs), and these reports may include a wide range of information including age, gender, and concomitant vaccines. Controlling for possible confounding variables such as these is an important task when utilizing surveillance systems to monitor post-market product safety. A common method for handling possible confounders is to compare observed product-AE combinations with adjusted baseline frequencies where the adjustments are made by stratifying on observable characteristics. Though approaches such as these have proven to be useful, in this article we propose a more flexible logistic regression approach which allows for covariates of all types rather than relying solely on stratification. Indeed, a main advantage of our approach is that the general regression framework provides flexibility to incorporate additional information such as demographic factors and concomitant vaccines. As part of our covariate-adjusted method, we outline a procedure for signal detection that accounts for multiple comparisons and controls the overall Type 1 error rate. To demonstrate the effectiveness of our approach, we illustrate our method with an example involving febrile convulsion, and we further evaluate its performance in a series of simulation studies.

Risk Factors and Birth Outcomes of Anaemia in Early Pregnancy in a Nulliparous Cohort

PubMed Central

Masukume, Gwinyai; Khashan, Ali S.; Kenny, Louise C.; Baker, Philip N.; Nelson, Gill

2015-01-01

Background Anaemia in pregnancy is a major public health and economic problem worldwide, that contributes to both maternal and fetal morbidity and mortality. Objective The aim of the study was to calculate the prevalence of anaemia in early pregnancy in a cohort of ‘low risk’ women participating in a large international multicentre prospective study (n = 5 609), to identify the modifiable risk factors for anaemia in pregnancy in this cohort, and to compare the birth outcomes between pregnancies with and without anaemia in early gestation. Methods The study is an analysis of data that were collected prospectively during the Screening for Pregnancy Endpoints study. Anaemia was defined according to the World Health Organization’s definition of anaemia in pregnancy (haemoglobin < 11g/dL). Binary logistic regression with adjustment for potential confounders (country, maternal age, having a marital partner, ethnic origin, years of schooling, and having paid work) was the main method of analysis. Results The hallmark findings were the low prevalence of anaemia (2.2%), that having no marital partner was an independent risk factor for having anaemia (OR 1.34, 95% CI 1.01-1.78), and that there was no statistically significant effect of anaemia on adverse pregnancy outcomes (small for gestational age, pre-tem birth, mode of delivery, low birth weight, APGAR score < 7 at one and five minutes). Adverse pregnancy outcomes were however more common in those with anaemia than in those without. Conclusion In this low risk healthy pregnant population we found a low anaemia rate. The absence of a marital partner was a non-modifiable factor, albeit one which may reflect a variety of confounding factors, that should be considered for addition to anaemia’s conceptual framework of determinants. Although not statistically significant, clinically, a trend towards a higher risk of adverse pregnancy outcomes was observed in women that were anaemic in early pregnancy. PMID:25875012

An introduction to instrumental variables analysis: part 1.

PubMed

Bennett, Derrick A

2010-01-01

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

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.

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

PubMed

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

2013-10-01

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

Evaluating the Impact of Implementation Factors on Family-Based Prevention Programming: Methods for Strengthening Causal Inference

PubMed Central

Crowley, D. Max; Coffman, Donna L.; Feinberg, Mark; Greenberg, Mark; Spoth, Richard

2013-01-01

Despite growing recognition of the important role implementation plays in successful prevention efforts, relatively little work has sought to demonstrate a causal relationship between implementation factors and participant outcomes. In turn, failure to explore the implementation-to-outcome link limits our understanding of the mechanisms essential to successful programming. This gap is partially due to the inability of current methodological procedures within prevention science to account for the multitude of confounders responsible for variation in implementation factors (i.e., selection bias). The current paper illustrates how propensity and marginal structural models can be used to improve causal inferences involving implementation factors not easily randomized (e.g., participant attendance). We first present analytic steps for simultaneously evaluating the impact of multiple implementation factors on prevention program outcome. Then we demonstrate this approach for evaluating the impact of enrollment and attendance in a family program, over and above the impact of a school-based program, within PROSPER, a large scale real-world prevention trial. Findings illustrate the capacity of this approach to successfully account for confounders that influence enrollment and attendance, thereby more accurately representing true causal relations. For instance, after accounting for selection bias, we observed a 5% reduction in the prevalence of 11th grade underage drinking for those who chose to receive a family program and school program compared to those who received only the school program. Further, we detected a 7% reduction in underage drinking for those with high attendance in the family program. PMID:23430578

The alarming problems of confounding equivalence using logistic regression models in the perspective of causal diagrams.

PubMed

Yu, Yuanyuan; Li, Hongkai; Sun, Xiaoru; Su, Ping; Wang, Tingting; Liu, Yi; Yuan, Zhongshang; Liu, Yanxun; Xue, Fuzhong

2017-12-28

Confounders can produce spurious associations between exposure and outcome in observational studies. For majority of epidemiologists, adjusting for confounders using logistic regression model is their habitual method, though it has some problems in accuracy and precision. It is, therefore, important to highlight the problems of logistic regression and search the alternative method. Four causal diagram models were defined to summarize confounding equivalence. Both theoretical proofs and simulation studies were performed to verify whether conditioning on different confounding equivalence sets had the same bias-reducing potential and then to select the optimum adjusting strategy, in which logistic regression model and inverse probability weighting based marginal structural model (IPW-based-MSM) were compared. The "do-calculus" was used to calculate the true causal effect of exposure on outcome, then the bias and standard error were used to evaluate the performances of different strategies. Adjusting for different sets of confounding equivalence, as judged by identical Markov boundaries, produced different bias-reducing potential in the logistic regression model. For the sets satisfied G-admissibility, adjusting for the set including all the confounders reduced the equivalent bias to the one containing the parent nodes of the outcome, while the bias after adjusting for the parent nodes of exposure was not equivalent to them. In addition, all causal effect estimations through logistic regression were biased, although the estimation after adjusting for the parent nodes of exposure was nearest to the true causal effect. However, conditioning on different confounding equivalence sets had the same bias-reducing potential under IPW-based-MSM. Compared with logistic regression, the IPW-based-MSM could obtain unbiased causal effect estimation when the adjusted confounders satisfied G-admissibility and the optimal strategy was to adjust for the parent nodes of outcome, which obtained the highest precision. All adjustment strategies through logistic regression were biased for causal effect estimation, while IPW-based-MSM could always obtain unbiased estimation when the adjusted set satisfied G-admissibility. Thus, IPW-based-MSM was recommended to adjust for confounders set.

Maternal Use of Corporal Punishment for 3-year-old Children and Subsequent Risk for Child Aggressive Behavior

PubMed Central

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

2016-01-01

OBJECTIVE To examine the association between maternal use of corporal punishment (CP) against their 3-year-old children and subsequent aggressive behavior among those children two years later. METHODS Respondents participated in waves 1, 3, and 5 of the Fragile Families and Child Wellbeing Study (1998–2005), a population-based longitudinal birth cohort study of children (and their parents) born in one of 20 large U.S. cities (n=2,461), with oversampling of unmarried couples. Maternal reports of CP, children’s aggressive behaviors at 3 and 5 years of age, and a host of key demographics and potential confounding factors were assessed including: child physical maltreatment, psychological maltreatment, and neglect, intimate partner aggression and violence, and maternal stress, depression, substance use, and consideration of abortion. RESULTS Multiple logistic regression analyses revealed that frequent use of CP (i.e., maternal use of spanking more than twice in the prior month) when the child was 3 years-old was associated with increased risk for higher levels of child aggression when the child was 5 years-old (adjusted odds ratio = 1.49 [CI=1.2–1.8] p<0.0001), even after simultaneously controlling for the child’s level of aggression at 3 years of age as well as all of the aforementioned confounding factors and key demographics. CONCLUSIONS Despite American Academy of Pediatrics recommendations to the contrary, most parents in the U.S. approve of and have used CP as a form of child discipline. The current findings support a growing body of evidence that even minor forms of CP, such as spanking, raise risk for increased subsequent child aggressive behavior. Importantly, these findings cannot be attributed to the possible confounding effects of a host of other maternal parenting risk factors. Increased and improved efforts to reduce the use of CP and promote the use of alternative, effective non-physical forms of child discipline among U.S. parents are warranted. PMID:20385647

Selection bias and patterns of confounding in cohort studies: the case of the NINFEA web-based birth cohort.

PubMed

Pizzi, Costanza; De Stavola, Bianca L; Pearce, Neil; Lazzarato, Fulvio; Ghiotti, Paola; Merletti, Franco; Richiardi, Lorenzo

2012-11-01

Several studies have examined the effects of sample selection on the exposure-outcome association estimates in cohort studies, but the reasons why this selection may induce bias have not been fully explored. To investigate how sample selection of the web-based NINFEA birth cohort may change the confounding patterns present in the source population. The characteristics of the NINFEA participants (n=1105) were compared with those of the wider source population-the Piedmont Birth Registry (PBR)-(n=36 092), and the association of two exposures (parity and educational level) with two outcomes (low birth weight and birth by caesarean section), while controlling for other risk factors, was studied. Specifically the associations among measured risk factors within each dataset were examined and the exposure-outcome estimates compared in terms of relative ORs. The associations of educational level with the other risk factors (alcohol consumption, folic acid intake, maternal age, pregnancy weight gain, previous miscarriages) partly differed between PBR and NINFEA. This was not observed for parity. Overall, the exposure-outcome estimates derived from NINFEA only differed moderately from those obtained in PBR, with relative ORs ranging between 0.74 and 1.03. Sample selection in cohort studies may alter the confounding patterns originally present in the general population. However, this does not necessarily introduce selection bias in the exposure-outcome estimates, as sample selection may reduce some of the residual confounding present in the general population.

Using change-point models to estimate empirical critical loads for nitrogen in mountain ecosystems.

PubMed

Roth, Tobias; Kohli, Lukas; Rihm, Beat; Meier, Reto; Achermann, Beat

2017-01-01

To protect ecosystems and their services, the critical load concept has been implemented under the framework of the Convention on Long-range Transboundary Air Pollution (UNECE) to develop effects-oriented air pollution abatement strategies. Critical loads are thresholds below which damaging effects on sensitive habitats do not occur according to current knowledge. Here we use change-point models applied in a Bayesian context to overcome some of the difficulties when estimating empirical critical loads for nitrogen (N) from empirical data. We tested the method using simulated data with varying sample sizes, varying effects of confounding variables, and with varying negative effects of N deposition on species richness. The method was applied to the national-scale plant species richness data from mountain hay meadows and (sub)alpine scrubs sites in Switzerland. Seven confounding factors (elevation, inclination, precipitation, calcareous content, aspect as well as indicator values for humidity and light) were selected based on earlier studies examining numerous environmental factors to explain Swiss vascular plant diversity. The estimated critical load confirmed the existing empirical critical load of 5-15 kg N ha -1 yr -1 for (sub)alpine scrubs, while for mountain hay meadows the estimated critical load was at the lower end of the current empirical critical load range. Based on these results, we suggest to narrow down the critical load range for mountain hay meadows to 10-15 kg N ha -1 yr -1 . Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.

PubMed

Kumar, Anil; Yadav, Anita; Giri, Shiv Kumar; Dev, Kapil; Gautam, Sanjeev Kumar; Gupta, Ranjan; Aggarwal, Neeraj

2011-07-01

In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chronic Fatigue and Personality: A Twin Study of Causal Pathways and Shared Liabilities

PubMed Central

Poeschla, Brian; Strachan, Eric; Dansie, Elizabeth; Buchwald, Dedra S.; Afari, Niloofar

2013-01-01

Background The etiology of chronic fatigue syndrome (CFS) remains unknown. Personality traits influence well-being and may play a role in CFS and unexplained chronic fatigue. Purpose To examine the association of emotional instability and extraversion with chronic fatigue and CFS in a genetically informative sample. Methods We evaluated 245 twin pairs for two definitions of chronic fatigue. They completed the Neuroticism and Extraversion subscales of the NEO-FFI. Using a co-twin control design, we examined the association between personality and chronic fatigue. Results Higher emotional instability was associated with both definitions of chronic fatigue and was confounded by shared genetics. Lower extraversion was also associated with both definitions of fatigue, but was not confounded by familial factors. Conclusions Both emotional instability and extraversion are related to chronic fatigue and CFS. Whereas emotional instability and chronic fatigue are linked by shared genetic mechanisms, the relationship with extraversion may be causal and bi-directional. PMID:23361410

Relative importance of climatic, geographic and socio-economic determinants of malaria in Malawi

PubMed Central

2013-01-01

Background Malaria transmission is influenced by variations in meteorological conditions, which impact the biology of the parasite and its vector, but also socio-economic conditions, such as levels of urbanization, poverty and education, which impact human vulnerability and vector habitat. The many potential drivers of malaria, both extrinsic, such as climate, and intrinsic, such as population immunity are often difficult to disentangle. This presents a challenge for the modelling of malaria risk in space and time. Methods A statistical mixed model framework is proposed to model malaria risk at the district level in Malawi, using an age-stratified spatio-temporal dataset of malaria cases from July 2004 to June 2011. Several climatic, geographic and socio-economic factors thought to influence malaria incidence were tested in an exploratory model. In order to account for the unobserved confounding factors that influence malaria, which are not accounted for using measured covariates, a generalized linear mixed model was adopted, which included structured and unstructured spatial and temporal random effects. A hierarchical Bayesian framework using Markov chain Monte Carlo simulation was used for model fitting and prediction. Results Using a stepwise model selection procedure, several explanatory variables were identified to have significant associations with malaria including climatic, cartographic and socio-economic data. Once intervention variations, unobserved confounding factors and spatial correlation were considered in a Bayesian framework, a final model emerged with statistically significant predictor variables limited to average precipitation (quadratic relation) and average temperature during the three months previous to the month of interest. Conclusions When modelling malaria risk in Malawi it is important to account for spatial and temporal heterogeneity and correlation between districts. Once observed and unobserved confounding factors are allowed for, precipitation and temperature in the months prior to the malaria season of interest are found to significantly determine spatial and temporal variations of malaria incidence. Climate information was found to improve the estimation of malaria relative risk in 41% of the districts in Malawi, particularly at higher altitudes where transmission is irregular. This highlights the potential value of climate-driven seasonal malaria forecasts. PMID:24228784

Understanding Antipsychotic Drug Treatment Effects: A Novel Method to Reduce Pseudospecificity of the Positive and Negative Syndrome Scale (PANSS) Factors.

PubMed

Hopkins, Seth C; Ogirala, Ajay; Loebel, Antony; Koblan, Kenneth S

2017-12-01

The Positive and Negative Syndrome Scale (PANSS) is the most widely used efficacy measure in acute treatment studies of schizophrenia. However, interpretation of the efficacy of antipsychotics in improving specific symptom domains is confounded by moderate-to-high correlations among standard (Marder) PANSS factors. The authors review the results of an uncorrelated PANSS score matrix (UPSM) transform designed to reduce pseudospecificity in assessment of symptom change in patients with schizophrenia. Based on a factor analysis of five pooled, placebo-controlled lurasidone clinical trials (N=1,710 patients), a UPSM transform was identified that generated PANSS factors with high face validity (good correlation with standard Marder PANSS factors), and high specificity/orthogonality (low levels of between-factor correlation measuring change during treatment). Between-factor correlations were low at baseline for both standard (Marder) PANSS factors and transformed PANSS factors. However, when measured change in symptom severity was measured during treatment (in a pooled 5-study analysis), there was a notable difference for standard PANSS factors, where changes across factors were found to be highly correlated (factors exhibited pseudospecificity), compared to transformed PANSS factors, where factor change scores exhibited the same low levels of between-factor correlation observed at baseline. At Week 6-endpoint, correlations among PANSS factor severity scores were moderate-to-high for standard factors (0.34-0.68), but continued to be low for the transformed factors (-0.22-0.20). As an additional validity check, we analyzed data from one of the original five pooled clinical trials that included other well-validated assessment scales (MADRS, Negative Symptom Assessment scale [NSA]). In this baseline analysis, UPSM-transformed PANSS factor severity scores (negative and depression factors) were found to correlate well with the MADRS and NSA. The availability of transformed PANSS factors with a high degree of orthogonality/specificity, but which retain a high degree of concurrent and face validity, can reduce pseudospecificity as a measurement confound, and should facilitate the drug development process, permitting a more accurate characterization of the efficacy of putative new agents in targeting specific symptom domains in patients with psychotic illness.

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.

Peer influence as a potential magnifier of ADHD diagnosis.

PubMed

Aronson, Brian

2016-11-01

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

Desire thinking as a confounder in the relationship between mindfulness and craving: Evidence from a cross-cultural validation of the Desire Thinking Questionnaire.

PubMed

Chakroun-Baggioni, Nadia; Corman, Maya; Spada, Marcantonio M; Caselli, Gabriele; Gierski, Fabien

2017-10-01

Desire thinking and mindfulness have been associated with craving. The aim of the present study was to validate the French version of the Desire Thinking Questionnaire (DTQ) and to investigate the relationship between mindfulness, desire thinking and craving among a sample of university students. Four hundred and ninety six university students completed the DTQ and measures of mindfulness, craving and alcohol use. Results from confirmatory factor analyses showed that the two-factor structure proposed in the original DTQ exhibited suitable goodness-of-fit statistics. The DTQ also demonstrated good internal reliability, temporal stability and predictive validity. A set of linear regressions revealed that desire thinking had a confounding effect in the relationship between mindfulness and craving. The confounding role of desire thinking in the relationship between mindfulness and craving suggests that interrupting desire thinking may be a viable clinical option aimed at reducing craving. Copyright © 2017 Elsevier B.V. All rights reserved.

Healthy Worker Effect Phenomenon: Revisited with Emphasis on Statistical Methods – A Review

PubMed Central

Chowdhury, Ritam; Shah, Divyang; Payal, Abhishek R.

2017-01-01

Known since 1885 but studied systematically only in the past four decades, the healthy worker effect (HWE) is a special form of selection bias common to occupational cohort studies. The phenomenon has been under debate for many years with respect to its impact, conceptual approach (confounding, selection bias, or both), and ways to resolve or account for its effect. The effect is not uniform across age groups, gender, race, and types of occupations and nor is it constant over time. Hence, assessing HWE and accounting for it in statistical analyses is complicated and requires sophisticated methods. Here, we review the HWE, factors affecting it, and methods developed so far to deal with it. PMID:29391741

Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

PubMed

Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

2012-12-01

Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard.

PubMed

Kang, Bo-Kyeong; Yu, Eun Sil; Lee, Seung Soo; Lee, Youngjoo; Kim, Namkug; Sirlin, Claude B; Cho, Eun Yoon; Yeom, Suk Keu; Byun, Jae Ho; Park, Seong Ho; Lee, Moon-Gyu

2012-06-01

The aims of this study were to assess the confounding effects of hepatic iron deposition, inflammation, and fibrosis on hepatic steatosis (HS) evaluation by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to assess the accuracies of MRI and MRS for HS evaluation, using histology as the reference standard. In this institutional review board-approved prospective study, 56 patients gave informed consents and underwent chemical-shift MRI and MRS of the liver on a 1.5-T magnetic resonance scanner. To estimate MRI fat fraction (FF), 4 analysis methods were used (dual-echo, triple-echo, multiecho, and multi-interference), and MRS FF was calculated with T2 correction. Degrees of HS, iron deposition, inflammation, and fibrosis were analyzed in liver resection (n = 37) and biopsy (n = 19) specimens. The confounding effects of histology on fat quantification were assessed by multiple linear regression analysis. Using the histologic degree of HS as the reference standard, the accuracies of each method in estimating HS and diagnosing an HS of 5% or greater were determined by linear regression and receiver operating characteristic analyses. Iron deposition significantly confounded estimations of FF by the dual-echo (P < 0.001) and triple-echo (P = 0.033) methods, whereas no histologic feature confounded the multiecho and multi-interference methods or MRS. The MRS (r = 0.95) showed the strongest correlation with histologic degree of HS, followed by the multiecho (r = 0.92), multi-interference (r = 0.91), triple-echo (r = 0.90), and dual-echo (r = 0.85) methods. For diagnosing HS, the areas under the curve tended to be higher for MRS (0.96) and the multiecho (0.95), multi-interference (0.95), and triple-echo (0.95) methods than for the dual-echo method (0.88) (P ≥ 0.13). The multiecho and multi-interference MRI methods and MRS can accurately quantify hepatic fat, with coexisting histologic abnormalities having no confounding effects.

Biomechanical and psychosocial exposures are independent risk factors for carpal tunnel syndrome: assessment of confounding using causal diagrams.

PubMed

Harris-Adamson, Carisa; Eisen, Ellen A; Neophytou, Andreas; Kapellusch, Jay; Garg, Arun; Hegmann, Kurt T; Thiese, Matthew S; Dale, Ann Marie; Evanoff, Bradley; Bao, Stephen; Silverstein, Barbara; Gerr, Fred; Burt, Susan; Rempel, David

2016-11-01

Between 2001 and 2010, six research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries to estimate exposure-response relationships. This analysis examined the presence and magnitude of confounding between biomechanical and workplace psychosocial factors and incidence of dominant-hand CTS. 1605 participants, without CTS at enrolment, were followed for up to 3.5 years (2471 person-years). Demographic information, medical history and workplace psychosocial stress measures were collected at baseline. Individual workplace biomechanical exposures were collected for each task and combined across the workweek using time-weighted averaging (TWA). CTS case criteria were based on symptoms and results of electrophysiological testing. HRs were estimated with Cox proportional hazard models. Confounding was assessed using causal diagrams and an empirical criterion of 10% or greater change in effect estimate magnitude. There were 109 incident CTS cases (IR=4.41/100 person-years; 6.7% cumulative incidence). The relationships between CTS and forceful repetition rate, % time forceful hand exertion and the Threshold Limit Value for Hand Activity Level (TLV-HAL) were slightly confounded by decision latitude with effect estimates being attenuated towards the null (10-14% change) after adjustment. The risk of CTS among participants reporting high job strain was attenuated towards the null by 14% after adjusting for the HAL Scale or the % time forceful hand exertions. Although attenuation of the relationships between CTS and some biomechanical and work psychosocial exposures was observed after adjusting for confounding, the magnitudes were small and confirmed biomechanical and work psychosocial exposures as independent risk factors for incident CTS. 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/.

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

PubMed

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

2016-04-01

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

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.

Bias magnification in ecologic studies: a methodological investigation

PubMed Central

Webster, Thomas F

2007-01-01

Background As ecologic studies are often inexpensive to conduct, consideration of the magnitude and direction of ecologic biases may be useful in both study design and sensitivity analysis of results. This paper examines three types of ecologic bias: confounding by group, effect measure modification by group, and non-differential exposure misclassification. Methods Bias of the risk difference on the individual and ecologic levels are compared using two-by-two tables, simple equations, and risk diagrams. Risk diagrams provide a convenient way to simultaneously display information from both levels. Results Confounding by group and effect measure modification by group act in the same direction on the individual and group levels, but have larger impact on the latter. The reduction in exposure variance caused by aggregation magnifies the individual level bias due to ignoring groups. For some studies, the magnification factor can be calculated from the ecologic data alone. Small magnification factors indicate little bias beyond that occurring at the individual level. Aggregation is also responsible for the different impacts of non-differential exposure misclassification on individual and ecologic studies. Conclusion The analytical tools developed here are useful in analyzing ecologic bias. The concept of bias magnification may be helpful in designing ecologic studies and performing sensitivity analysis of their results. PMID:17615079

Maternal pre-pregnancy obesity and neuropsychological development in pre-school children: a prospective cohort study.

PubMed

Casas, Maribel; Forns, Joan; Martínez, David; Guxens, Mònica; Fernandez-Somoano, Ana; Ibarluzea, Jesus; Lertxundi, Nerea; Murcia, Mario; Rebagliato, Marisa; Tardon, Adonina; Sunyer, Jordi; Vrijheid, Martine

2017-10-01

BackgroundMaternal pre-pregnancy obesity may impair infant neuropsychological development, but it is unclear whether intrauterine or confounding factors drive this association.MethodsWe assessed whether maternal pre-pregnancy obesity was associated with neuropsychological development in 1,827 Spanish children. At 5 years, cognitive and psychomotor development was assessed using McCarthy Scales of Children's Abilities, attention deficit hyperactivity disorder (ADHD) symptoms using the Criteria of Diagnostic and Statistical Manual of Mental Disorders, and autism spectrum disorder symptoms using the Childhood Asperger Syndrome Test. Models were adjusted for sociodemographic factors and maternal intelligence quotient. We used paternal obesity as negative control exposure as it involves the same source of confounding than maternal obesity.ResultsThe percentage of obese mothers and fathers was 8% and 12%, respectively. In unadjusted models, children of obese mothers had lower scores than children of normal weight mothers in all McCarthy subscales. After adjustment, only the verbal subscale remained statistically significantly reduced (β: -2.8; 95% confidence interval: -5.3, -0.2). No associations were observed among obese fathers. Maternal and paternal obesity were associated with an increase in ADHD-related symptoms. Parental obesity was not associated with autism symptoms.ConclusionMaternal pre-pregnancy obesity was associated with a reduction in offspring verbal scores at pre-school age.

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

PubMed Central

Micek, Agnieszka; Marranzano, Marina; Ray, Sumantra

2017-01-01

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

Is hypertension in adult age related to unemployment at a young age? Results from the Northern Swedish Cohort.

PubMed

Nygren, Karina; Gong, Weidan; Hammarström, Anne

2015-02-01

The aim of this study was to analyse the relationship between early unemployment (ages 16-21 years) and adult hypertension after controlling for earlier hypertension, unemployment in adult life, risk factors for hypertension and confounders. A cohort of 927 (86.6% of the original cohort) 9th grade school-leavers was followed from 1981 until 2008. Data were collected through questionnaires, health examinations, and national registers. Univariate and multivariate logistic regression were used as primary statistical methods. At ages 21 and 43, hypertension was significantly more prevalent among men than women (p < .001). Unemployment between the ages of 16 and 21 was related to hypertension at age 43 among women but not men. The odds ratio (OR) was persistently high (OR 3.16 [95% confidence interval 1.45-6.89]) after controlling for late unemployment, hypertension at age 16, risk factors for hypertension and confounders. There was no significant relationship between exposure to early unemployment and hypertension at age 21 for women or men. From a public health perspective, youth unemployment is a societal problem in need of more attention and intervention in order to prevent long-term adverse health outcomes. © 2014 the Nordic Societies of Public Health.

Associations between workplace factors and carpal tunnel syndrome: A multi-site cross sectional study.

PubMed

Fan, Z Joyce; Harris-Adamson, Carisa; Gerr, Fred; Eisen, Ellen A; Hegmann, Kurt T; Bao, Stephen; Silverstein, Barbara; Evanoff, Bradley; Dale, Ann Marie; Thiese, Matthew S; Garg, Arun; Kapellusch, Jay; Burt, Susan; Merlino, Linda; Rempel, David

2015-05-01

Few large epidemiologic studies have used rigorous case criteria, individual-level exposure measurements, and appropriate control for confounders to examine associations between workplace psychosocial and biomechanical factors and carpal tunnel syndrome (CTS). Pooling data from five independent research studies, we assessed associations between prevalent CTS and personal, work psychosocial, and biomechanical factors while adjusting for confounders using multivariable logistic regression. Prevalent CTS was associated with personal factors of older age, obesity, female sex, medical conditions, previous distal upper extremity disorders, workplace measures of peak forceful hand activity, a composite measure of force and repetition (ACGIH Threshold Limit Value for Hand Activity Level), and hand vibration. In this cross-sectional analysis of production and service workers, CTS prevalence was associated with workplace and biomechanical factors. The findings were similar to those from a prospective analysis of the same cohort with differences that may be due to recall bias and other factors. © 2015 Wiley Periodicals, Inc.

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

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.

Evaluation in medical education: A topical review of target parameters, data collection tools and confounding factors.

PubMed

Schiekirka, Sarah; Feufel, Markus A; Herrmann-Lingen, Christoph; Raupach, Tobias

2015-01-01

Evaluation is an integral part of education in German medical schools. According to the quality standards set by the German Society for Evaluation, evaluation tools must provide an accurate and fair appraisal of teaching quality. Thus, data collection tools must be highly reliable and valid. This review summarises the current literature on evaluation of medical education with regard to the possible dimensions of teaching quality, the psychometric properties of survey instruments and potential confounding factors. We searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical education and included studies published up until June 30, 2011 as well as articles identified in the "grey literature". RESULTS are presented as a narrative review. We identified four dimensions of teaching quality: structure, process, teacher characteristics, and outcome. Student ratings are predominantly used to address the first three dimensions, and a number of reliable tools are available for this purpose. However, potential confounders of student ratings pose a threat to the validity of these instruments. Outcome is usually operationalised in terms of student performance on examinations, but methodological problems may limit the usability of these data for evaluation purposes. In addition, not all examinations at German medical schools meet current quality standards. The choice of tools for evaluating medical education should be guided by the dimension that is targeted by the evaluation. Likewise, evaluation results can only be interpreted within the context of the construct addressed by the data collection tool that was used as well as its specific confounding factors.

Prevalence of hypertension and noise-induced hearing loss in Chinese coal miners

PubMed Central

Liu, Jing; Xu, Ming; Ding, Lu; Zhang, Hengdong; Pan, Liping; Liu, Qingdong; Ding, Enming; Zhao, Qiuni; Wang, Boshen; Han, Lei

2016-01-01

Background Owing to inconsistent epidemiologic evidence and the presence of confounding factors, the relation between occupational noise exposure and hypertension still remained unclear. We aimed to assess whether Chinese coal miners were at risk of developing hypertension and noise induced hearing loss (NIHL), and whether occupational noise exposure was a risk factor of hypertension. Methods A questionnaire was designed to collect information from 738 study participants, all of whom were employees from the Datun Xuzhou Coal Company. The participants were divided into a noise-exposed group and a control group based on the noise level to which they were exposed in the workplace. The differences in the mean of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were compared between the noise-exposed and control groups. Also the prevalence and age-adjusted odds ratio (OR) [95% confidence intervals (CIs)] of audiometric deficit and hypertension was compared in the study. Binary logistic regression was used to assess the relation between occupational noise level and hypertension while controlling for potential confounding factors. Results Hypertension was more prevalent in noise-exposed group than the control group, 29.2% vs. 21.2% (P=0.012). The noise-exposed group faced an increased risk of hypertension (age-adjusted OR =1.52, 95% CI =1.07–2.15) when the control group was used as reference. The mean values of SBP and DBP of the noise-exposed groups were significantly higher than the control group (P=0.006 and P=0.002 respectively). Hearing loss at low frequencies was significantly more prevalent in the noise-exposed group than the control group, 12.8% vs. 7.4% (P=0.015), while the noise-exposed group faced the increased risk of hearing loss at low frequencies (age-adjusted OR =1.81, 95% CI =1.10–2.96). LEX, 8h (OR =1.036, 95% CI =1.012–1.060) was an independent risk of hypertension when controlling for potential confounding factors. Conclusions We found that the occupational noise had an effect on the hypertension and hearing loss of Chinese coal miners. And the occupational noise was an independent risk factor for hypertension and could increase the values of SBP and DBP. PMID:27076937

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

PubMed Central

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-01-01

Objective To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk for overall major congenital, cardiac, and central nervous system (CNS) malformations. Methods We used a cohort of completed pregnancies linked to liveborn infants derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. Results The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor–exposed was 5.9% versus 3.3% in the unexposed (unadjusted relative risk (RR), 1.82; 95% confidence interval (CI) 1.61 to 2.06), of cardiac malformations was 3.4% versus 1.2% (RR 2.95; 95% CI 2.50 to 3.47), and of CNS malformations was 0.27% versus 0.18% (RR 1.46; 95% CI 0.81 to 2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk for any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75 to 1.06) for overall malformations, 0.95 (95% CI 0.75 to 1.21) for cardiac malformations, and 0.54 (95% CI 0.26 to 1.11) for CNS malformations. Conclusions After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations. PMID:27926639

PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances.

PubMed

Tang, Zheng-Zheng; Chen, Guanhua; Alekseyenko, Alexander V

2016-09-01

Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance-based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances

PubMed Central

Tang, Zheng-Zheng; Chen, Guanhua; Alekseyenko, Alexander V.

2016-01-01

Motivation: Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. Results: We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance-based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. Availability and Implementation: miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile. Contact: z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27197815

The association of educational attainment and SBP among older community-living adults: the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly (MOBILIZE) Boston Study

PubMed Central

Kiely, Dan K.; Gross, Alden L.; Kim, Dae H.; Lipsitz, Lewis A.

2012-01-01

Objective Educational attainment is inversely associated with SBP level in young adulthood. This association has not been studied in an older cohort, and confounding and mediating factors are not well known. Methods The authors hypothesized that higher education is associated with lower levels of SBP independent of many risk factors for hypertension. This prospective observational study included a sample of 764 older community-living participants in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly (MOBILIZE) Boston Study. Results Compared to participants with more than college education, regression analyses showed those with a high school education or less had a SBP value 6.33 mmHg higher [95% confidence interval (CI): 2.55–10.10], and those who had a college education had a SBP value 4.01 mmHg higher (95% CI: 0.77–7.25) independent of many hypothesized confounders and mediators. Discussion Results of a path analysis confirmed that higher level of education was associated with lower SBP even after adjustment for hypothesized mediators. Although slightly attenuated by multivariable adjustment for hypertension risk factors, the significant inverse association between educational attainment and SBP was not entirely mediated by these risk factors. These findings indicate that education is inversely associated with SBP in a diverse cohort of community-living older adults, independent of many known or suspected risk factors. Conclusion This study is the first to report the association between education and SBP in an older sample, representing a population at the highest risk for hypertension-related morbidity and mortality. PMID:22688267

Male fertility: psychiatric considerations.

PubMed

Hall, Elise; Burt, Vivien K

2012-02-01

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

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

Fat Quantification in the Abdomen.

PubMed

Hong, Cheng William; Fazeli Dehkordy, Soudabeh; Hooker, Jonathan C; Hamilton, Gavin; Sirlin, Claude B

2017-12-01

Fatty liver disease is characterized histologically by hepatic steatosis, the abnormal accumulation of lipid in hepatocytes. It is classified into alcoholic fatty liver disease and nonalcoholic fatty liver disease, and is an increasingly important cause of chronic liver disease and cirrhosis. Assessing the severity of hepatic steatosis in these conditions is important for diagnostic and prognostic purposes, as hepatic steatosis is potentially reversible if diagnosed early. The criterion standard for assessing hepatic steatosis is liver biopsy, which is limited by sampling error, its invasive nature, and associated morbidity. As such, noninvasive imaging-based methods of assessing hepatic steatosis are needed. Ultrasound and computed tomography are able to suggest the presence of hepatic steatosis based on imaging features, but are unable to accurately quantify hepatic fat content. Since Dixon's seminal work in 1984, magnetic resonance imaging has been used to compute the signal fat fraction from chemical shift-encoded imaging, commonly implemented as out-of-phase and in-phase imaging. However, signal fat fraction is confounded by several factors that limit its accuracy and reproducibility. Recently, advanced chemical shift-encoded magnetic resonance imaging methods have been developed that address these confounders and are able to measure the proton density fat fraction, a standardized, accurate, and reproducible biomarker of fat content. The use of these methods in the liver, as well as in other abdominal organs such as the pancreas, adrenal glands, and adipose tissue will be discussed in this review.

Prevalence of cholera risk factors between migrant Haitians and Dominicans in the Dominican Republic.

PubMed

Lund, Andrea J; Keys, Hunter M; Leventhal, Stephanie; Foster, Jennifer W; Freeman, Matthew C

2015-03-01

To determine whether cholera risk factor prevalence in the Dominican Republic can be explained by nationality, independent of other factors, given the vulnerability of many Haitians in the country and the need for targeted prevention. A cross-sectional, observational household survey (103 Haitian and 260 Dominican) was completed in 18 communities in July 2012. The survey included modules for demographics, knowledge, socioeconomic status, and access to adequate water, sanitation, and hygiene (WASH) infrastructure. Logistic regression assessed differential access to WASH infrastructure and Poisson regression assessed differences in cholera knowledge, controlling for potential confounders. Dominican and Haitian households differed on demographic characteristics. Haitians had lower educational attainment, socioeconomic status, and less knowledge of cholera than Dominicans (adjusted odds ratio [aOR] = 0.66; 95% confidence interval [95%CI] = 0.55-0.81). Access to improved drinking water was low for both groups, but particularly low among rural Haitians (aOR = 0.21; 95%CI: 0.04-1.01). No differences were found in access to sanitation after adjusting for sociodemographic confounders (aOR = 1.00; 95%CI: 0.57-1.76). Urban/rural geography and socioeconomic status play a larger role in cholera risk factor prevalence than nationality, indicating that Haitians' perceived vulnerability to cholera is confounded by contextual factors. Understanding the social dynamics that lead to cholera risk can inform control strategies, leading to better targeting and the possibility of eliminating cholera from the island.

Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communities study

PubMed Central

2012-01-01

Introduction There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities. Methods This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level). Results Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57). Conclusion We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear. PMID:22906142

Risk profiles for weight gain among postmenopausal women: A classification and regression tree analysis approach

USDA-ARS?s Scientific Manuscript database

Risk factors for obesity and weight gain are typically evaluated individually while "adjusting for" the influence of other confounding factors, and few studies, if any, have created risk profiles by clustering risk factors. We identified subgroups of postmenopausal women homogeneous in their cluster...

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

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

PubMed

Jackson, John W

2016-11-01

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

Technical note: Comparison of metal-on-metal hip simulator wear measured by gravimetric, CMM and optical profiling methods

NASA Astrophysics Data System (ADS)

Alberts, L. Russell; Martinez-Nogues, Vanesa; Baker Cook, Richard; Maul, Christian; Bills, Paul; Racasan, R.; Stolz, Martin; Wood, Robert J. K.

2018-03-01

Simulation of wear in artificial joint implants is critical for evaluating implant designs and materials. Traditional protocols employ the gravimetric method to determine the loss of material by measuring the weight of the implant components before and after various test intervals and after the completed test. However, the gravimetric method cannot identify the location, area coverage or maximum depth of the wear and it has difficulties with proportionally small weight changes in relatively heavy implants. In this study, we compare the gravimetric method with two geometric surface methods; an optical light method (RedLux) and a coordinate measuring method (CMM). We tested ten Adept hips in a simulator for 2 million cycles (MC). Gravimetric and optical methods were performed at 0.33, 0.66, 1.00, 1.33 and 2 MC. CMM measurements were done before and after the test. A high correlation was found between the gravimetric and optical methods for both heads (R 2  =  0.997) and for cups (R 2  =  0.96). Both geometric methods (optical and CMM) measured more volume loss than the gravimetric method (for the heads, p  =  0.004 (optical) and p  =  0.08 (CMM); for the cups p  =  0.01 (optical) and p  =  0.003 (CMM)). Two cups recorded negative wear at 2 MC by the gravimetric method but none did by either the optical method or by CMM. The geometric methods were prone to confounding factors such as surface deformation and the gravimetric method could be confounded by protein absorption and backside wear. Both of the geometric methods were able to show the location, area covered and depth of the wear on the bearing surfaces, and track their changes during the test run; providing significant advantages to solely using the gravimetric method.

Comparative performance of two quantitative safety signalling methods: implications for use in a pharmacovigilance department.

PubMed

Almenoff, June S; LaCroix, Karol K; Yuen, Nancy A; Fram, David; DuMouchel, William

2006-01-01

There is increasing interest in using disproportionality-based signal detection methods to support postmarketing safety surveillance activities. Two commonly used methods, empirical Bayes multi-item gamma Poisson shrinker (MGPS) and proportional reporting ratio (PRR), perform differently with respect to the number and types of signals detected. The goal of this study was to compare and analyse the performance characteristics of these two methods, to understand why they differ and to consider the practical implications of these differences for a large, industry-based pharmacovigilance department. We compared the numbers and types of signals of disproportionate reporting (SDRs) obtained with MGPS and PRR using two postmarketing safety databases and a simulated database. We recorded signal counts and performed a qualitative comparison of the drug-event combinations signalled by the two methods as well as a sensitivity analysis to better understand how the thresholds commonly used for these methods impact their performance. PRR detected more SDRs than MGPS. We observed that MGPS is less subject to confounding by demographic factors because it employs stratification and is more stable than PRR when report counts are low. Simulation experiments performed using published empirical thresholds demonstrated that PRR detected false-positive signals at a rate of 1.1%, while MGPS did not detect any statistical false positives. In an attempt to separate the effect of choice of signal threshold from more fundamental methodological differences, we performed a series of experiments in which we modified the conventional threshold values for each method so that each method detected the same number of SDRs for the example drugs studied. This analysis, which provided quantitative examples of the relationship between the published thresholds for the two methods, demonstrates that the signalling criterion published for PRR has a higher signalling frequency than that published for MGPS. The performance differences between the PRR and MGPS methods are related to (i) greater confounding by demographic factors with PRR; (ii) a higher tendency of PRR to detect false-positive signals when the number of reports is small; and (iii) the conventional thresholds that have been adapted for each method. PRR tends to be more 'sensitive' and less 'specific' than MGPS. A high-specificity disproportionality method, when used in conjunction with medical triage and investigation of critical medical events, may provide an efficient and robust approach to applying quantitative methods in routine postmarketing pharmacovigilance.

Persistent smoking as a predictor of disability pension due to musculoskeletal diagnoses: a 23 year prospective study of Finnish twins.

PubMed

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

2013-12-01

To investigate whether stability or changes in smoking predict disability pension (DP) due to low back diagnoses (LBD) and musculoskeletal diagnoses (MSD) after taking familial confounding into account using a co-twin design. Longitudinal smoking patterns and multiple covariates in a population-based cohort of 17,451 Finnish twins (6959 complete pairs) born before 1958 were surveyed through questionnaires in 1975 and 1981. The outcome data were collected from the national pension registers until the end of 2004. Cox proportional hazards regression models were used for statistical analyses. Disability pension due to low back diagnoses was granted to 408 individuals and disability pension due to musculoskeletal diagnoses to 1177 individuals during the follow-up of 23 years. Being a persistent smoker (current smoker both 1975 and 1981) predicted a significantly increased risk for disability pension (hazard ratio 1.69, 95% confidence interval 1.46, 1.97) compared to those individuals who had never smoked. The association remained when several confounding factors, including familial factors, were taken into account. Persistent smoking predicts early disability pension due to musculoskeletal diagnoses and low back diagnoses independently from numerous confounding factors, including familial effects shared by the co-twins. © 2013.

Success Providing Postpartum Intrauterine Devices in Private-Sector Health Care Facilities in Nigeria: Factors Associated With Uptake

PubMed Central

Eluwa, George IE; Atamewalen, Ronke; Odogwu, Kingsley; Ahonsi, Babatunde

2016-01-01

ABSTRACT Background: Use of modern contraceptive methods in Nigeria remained at 10% between 2008 and 2013 despite substantive investments in family planning services. Many women in their first postpartum year, in particular, have an unmet need for family planning. We evaluated use of postpartum intrauterine device (IUD) insertion and determined factors associated with its uptake in Nigeria. Methods: Data were collected between May 2014 and February 2015 from 11 private health care facilities in 6 southern Nigerian states. Women attending antenatal care in participating facilities were counseled on all available contraceptive methods including the postpartum IUD. Data were abstracted from participating facility records and evaluated using a cross-sectional analysis. Categorical variables were calculated as proportions while continuous variables were calculated as medians with the associated interquartile range (IQR). Multivariate logistic regression analysis was used to identify factors associated with uptake of the postpartum IUD while controlling for potential confounding factors, including age, educational attainment, marital status, parity, number of living children, and previous use of contraception. Results: During the study period, 728 women delivered in the 11 facilities. The median age was 28 years, and most women were educated (73% had completed at least the secondary level). The majority (96%) of the women reported they were married, and the median number of living children was 3 (IQR, 2–4). Uptake of the postpartum IUD was 41% (n = 300), with 8% (n = 25) of the acceptors experiencing expulsion of the IUD within 6 weeks post-insertion. After controlling for potential confounding factors, several characteristics were associated with greater likelihood of choosing the postpartum IUD, including lower education, having a higher number of living children, and being single. Women who had used contraceptives previously were less likely to choose the postpartum IUD than women who had not previously used contraception (adjusted odds ratio, 0.68; 95% confidence interval, 0.55 to 0.84). Conclusion: A high percentage (41%) of women delivering in private health care facilities in southern Nigeria accepted immediate postpartum IUD insertion. Scale-up of postpartum IUD services is a promising approach to increasing uptake of long-acting reversible contraceptives among women in Nigeria. PMID:27353620

Maternal and Paternal Height and the Risk of Preeclampsia.

PubMed

Lee, Yunsung; Magnus, Per

2018-04-01

The etiology of preeclampsia is unknown. Tall women have been found to have lower incidence of preeclampsia. This points to a possible biological causal effect but may be because of socioeconomic confounding. We used paternal height as an unexposed control to examine confounding. The MoBa (Norwegian Mother and Child Cohort Study) was used to extract data on parental heights, maternal prepregnancy weight, other background factors, and pregnancy outcomes for 99 968 singleton births. Multiple logistic regression was used to estimate odds ratios for preeclampsia according to parental height. The adjusted odds ratio for preeclampsia was 0.74 (95% CI, 0.66-0.82) for women >172 cm as compared with women <164 cm. The adjusted odds ratio for preeclampsia for men >186 cm was 1.03 (95% CI, 0.93-1.15) compared with men <178 cm. The association between maternal height and preeclampsia is unlikely to be because of confounding by familial, socioeconomic factors or by fetal genes related to height. The observed association between maternal height and preeclampsia merits further investigation. © 2018 American Heart Association, Inc.

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.

Associations between otitis media and child behavioural and learning difficulties: Results from a Danish cohort.

PubMed

Niclasen, J; Obel, C; Homøe, P; Kørvel-Hanquist, A; Dammeyer, J

2016-05-01

Findings from studies investigating early childhood episodes of otitis media (OM) and developmental outcomes are inconclusive. This may in part be because large-scale prospective studies controlling for relevant confounding factors are sparse. The present study investigates associations between OM in early childhood and later behavioural and learning difficulties controlling for relevant confounding factors. The study applied data from the Aarhus Birth Cohort's 10-12-year-old follow-up (N=7578). Associations between retrospective parent-reported OM (no OM; 1-3 episodes of OM with/without tympanostomy tubes; 4+ OM episodes without tympanostomy tubes and; 4+ OM episodes with tympanostomy tubes) one the one hand, and parent- and teacher-reported scores on the Strengths and Difficulties Questionnaire (SDQ) and parent-reported academic difficulties on the other hand, were investigated. The following variables were controlled for: parental educational level, maternal and paternal school problems, parental post-natal smoking, breastfeeding, and age at which the child started walking. All analyses were stratified by gender. Large differences in background characteristics were observed for the group of children with 4+ OM episodes with tympanostomy tubes compared to the no OM group. After controlling for relevant confounders, negative associations were consistently observed for the group of children with 4+ episodes of OM with tympanostomy tubes compared to the group of children without OM. This was particularly so for girls. The findings suggest an association between 4+ episodes of early OM with tympanostomy tubes and behavioural and learning difficulties later in childhood. The large inter-group differences, i.e. impact of residual and unmeasured confounding factors, may in part explain the observed associations and underline the need to include these in future studies. Copyright © 2016. Published by Elsevier Ireland Ltd.

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

PubMed

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

2015-03-15

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

Who really gets strep sore throat? Confounding and effect modification of a time-varying exposure on recurrent events.

PubMed

Follmann, Dean; Huang, Chiung-Yu; Gabriel, Erin

2016-10-30

Unmeasured confounding is the fundamental obstacle to drawing causal conclusions about the impact of an intervention from observational data. Typically, covariates are measured to eliminate or ameliorate confounding, but they may be insufficient or unavailable. In the special setting where a transient intervention or exposure varies over time within each individual and confounding is time constant, a different tack is possible. The key idea is to condition on either the overall outcome or the proportion of time in the intervention. These measures can eliminate the unmeasured confounding either by conditioning or by use of a proxy covariate. We evaluate existing methods and develop new models from which causal conclusions can be drawn from such observational data even if no baseline covariates are measured. Our motivation for this work was to determine the causal effect of Streptococcus bacteria in the throat on pharyngitis (sore throat) in Indian schoolchildren. Using our models, we show that existing methods can be badly biased and that sick children who are rarely colonized have a high probability that the Streptococcus bacteria are causing their disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Success Providing Postpartum Intrauterine Devices in Private-Sector Health Care Facilities in Nigeria: Factors Associated With Uptake.

PubMed

Eluwa, George Ie; Atamewalen, Ronke; Odogwu, Kingsley; Ahonsi, Babatunde

2016-06-20

Use of modern contraceptive methods in Nigeria remained at 10% between 2008 and 2013 despite substantive investments in family planning services. Many women in their first postpartum year, in particular, have an unmet need for family planning. We evaluated use of postpartum intrauterine device (IUD) insertion and determined factors associated with its uptake in Nigeria. Data were collected between May 2014 and February 2015 from 11 private health care facilities in 6 southern Nigerian states. Women attending antenatal care in participating facilities were counseled on all available contraceptive methods including the postpartum IUD. Data were abstracted from participating facility records and evaluated using a cross-sectional analysis. Categorical variables were calculated as proportions while continuous variables were calculated as medians with the associated interquartile range (IQR). Multivariate logistic regression analysis was used to identify factors associated with uptake of the postpartum IUD while controlling for potential confounding factors, including age, educational attainment, marital status, parity, number of living children, and previous use of contraception. During the study period, 728 women delivered in the 11 facilities. The median age was 28 years, and most women were educated (73% had completed at least the secondary level). The majority (96%) of the women reported they were married, and the median number of living children was 3 (IQR, 2-4). Uptake of the postpartum IUD was 41% (n = 300), with 8% (n = 25) of the acceptors experiencing expulsion of the IUD within 6 weeks post-insertion. After controlling for potential confounding factors, several characteristics were associated with greater likelihood of choosing the postpartum IUD, including lower education, having a higher number of living children, and being single. Women who had used contraceptives previously were less likely to choose the postpartum IUD than women who had not previously used contraception (adjusted odds ratio, 0.68; 95% confidence interval, 0.55 to 0.84). A high percentage (41%) of women delivering in private health care facilities in southern Nigeria accepted immediate postpartum IUD insertion. Scale-up of postpartum IUD services is a promising approach to increasing uptake of long-acting reversible contraceptives among women in Nigeria. © Eluwa et al.

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

PubMed

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

2018-03-01

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

Adaptive design of visual perception experiments

NASA Astrophysics Data System (ADS)

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

2010-04-01

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

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

DTIC Science & Technology

1999-10-01

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

Concepts and considerations of tooth wear: Part II--The mechanical component.

PubMed

Raigrodski, Ariel J; Dogan, Sami

2008-05-01

Identification of etiological factors is essential for successful management of tooth wear. In many cases, the diagnosis may be complicated because of the multiple etiologic factors which may confound the clinical appearance of tooth wear. Comprehensively addressing all of these factors is paramount to the long-term success of patient management.

Is the Association between General Cognitive Ability and Violent Crime Caused by Family-Level Confounders?

PubMed Central

Frisell, Thomas; Pawitan, Yudi; Långström, Niklas

2012-01-01

Background Research has consistently found lower cognitive ability to be related to increased risk for violent and other antisocial behaviour. Since this association has remained when adjusting for childhood socioeconomic position, ethnicity, and parental characteristics, it is often assumed to be causal, potentially mediated through school adjustment problems and conduct disorder. Socioeconomic differences are notoriously difficult to quantify, however, and it is possible that the association between intelligence and delinquency suffer substantial residual confounding. Methods We linked longitudinal Swedish total population registers to study the association of general cognitive ability (intelligence) at age 18 (the Conscript Register, 1980–1993) with the incidence proportion of violent criminal convictions (the Crime Register, 1973–2009), among all men born in Sweden 1961–1975 (N = 700,514). Using probit regression, we controlled for measured childhood socioeconomic variables, and further employed sibling comparisons (family pedigree data from the Multi-Generation Register) to adjust for shared familial characteristics. Results Cognitive ability in early adulthood was inversely associated to having been convicted of a violent crime (β = −0.19, 95% CI: −0.19; −0.18), the association remained when adjusting for childhood socioeconomic factors (β = −0.18, 95% CI: −0.18; −0.17). The association was somewhat lower within half-brothers raised apart (β = −0.16, 95% CI: −0.18; −0.14), within half-brothers raised together (β = −0.13, 95% CI: (−0.15; −0.11), and lower still in full-brother pairs (β = −0.10, 95% CI: −0.11; −0.09). The attenuation among half-brothers raised together and full brothers was too strong to be attributed solely to attenuation from measurement error. Discussion Our results suggest that the association between general cognitive ability and violent criminality is confounded partly by factors shared by brothers. However, most of the association remains even after adjusting for such factors. PMID:22911856

Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance

PubMed Central

Darbà, Josep; Ramírez, Gabriela; Sicras, Antoni; García-Bujalance, Laura; Torvinen, Saku; Sánchez-de la Rosa, Rainel

2016-01-01

Objective To identify the impact of delivery device of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA) on asthma medication compliance, and investigate other factors associated with compliance. Materials and methods We conducted a retrospective and multicenter study based on a review of medical registries of asthmatic patients treated with ICS/LABA combinations (n=2,213) whose medical devices were either dry powder inhalers (DPIs, such as Accuhaler®, Turbuhaler®, and NEXThaler®) or pressurized metered-dose inhalers (pMDI). Medication compliance included persistence outcomes through 18 months and medication possession ratios. Data on potential confounders of treatment compliance such as asthma exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also explored. Results The probability of asthma medication compliance in case of DPIs was lower compared to pMDIs, which suggests that inhaler devices influence inhalation therapies. There were additional confounding factors that were considered as explanatory variables of compliance. A worse measure of airflow obstruction (forced expiration volume in 1 second), comorbidities and general practitioner (GP) consultations more than once per month decreased the probability of compliance. Within comorbidities, alcoholism was positively associated with compliance. Patients of 29–39, 40–50, and 51–61 age groups or suffering from more than two exacerbations during the study period were more likely to comply with their medication regime. The effects of DPIs toward compliance varied with the different DPIs. For instance, Accuhaler® had a greater negative effect on compliance compared to Turbuhaler® and Nexthaler® in cases of patients who suffered exacerbations. We found that GP consultations reduced the probability of medication compliance for patients treated with formoterol/budesonide combination. For retired patients, visiting the GP increased the probability of medication compliance. Conclusion We concluded that inhaler devices influence patients’ compliance for long-term asthma medication. The impact of Accuhaler®, Turbuhaler®, and NEXThaler® on medication compliance was negative. We also identified some confounders of medication compliance such as patient’s age, severity of asthma, comorbidities, and health care costs. PMID:26929605

Psychosocial and socioeconomic determinants of cardiovascular mortality in Eastern Europe: A multicentre prospective cohort study

PubMed Central

Kubinova, Ruzena; Tamosiunas, Abdonas; Marmot, Michael; Bobak, Martin

2017-01-01

Background Eastern European countries have some of the highest rates of cardiovascular disease (CVD) mortality, much of which cannot be adequately accounted for by conventional CVD risk factors. Psychosocial and socioeconomic factors may affect risk of CVD, but relatively few studies on this issue have been undertaken in Eastern Europe. We investigated whether various psychosocial factors are associated with CVD mortality independently from each other and whether they can help explain differences in CVD mortality between Eastern European populations. Methods Participants were from the Health, Alcohol and Psychological factors in Eastern Europe (HAPIEE) cohort study in Russia, Poland and the Czech Republic, including a total of 20,867 men and women aged 43–74 years and free of CVD at baseline examination during 2002–2005. Participants were followed-up for CVD mortality after linkage to national mortality registries for a median of 7.2 years. Results During the follow-up, 556 participants died from CVD. After mutual adjustment, six psychosocial and socioeconomic factors were associated with increased risk of CVD death: unemployment, low material amenities, depression, being single, infrequent contacts with friends or relatives. The hazard ratios [HRs] for these six factors ranged between 1.26 [95% confidence interval 1.14–1.40] and 1.81 [95% confidence interval 1.24–2.64], fully adjusted for each other, and conventional cardiovascular risk factors. Population-attributable fractions ranged from 8% [4%–13%] to 22% [11%–31%] for each factor, when measured on average across the three cohorts. However, the prevalence of psychosocial and socioeconomic risk factors and their HRs were similar between the three countries. Altogether, these factors could not explain why participants from Russia had higher CVD mortality when compared to participants from Poland/Czech Republic. Limitations of this study include measurement error that could lead to residual confounding; and the possibilities for reverse causation and/or unmeasured confounding from observational studies to lead to associations that are not causal in nature. Conclusions Six psychosocial and socioeconomic factors were associated with cardiovascular mortality, independent of each other. Differences in mortality between cohorts from Russia versus Poland or Check Republic remained unexplained. PMID:29211726

Systematic review of the quality of prognosis studies in systemic lupus erythematosus.

PubMed

Lim, Lily S H; Lee, Senq J; Feldman, Brian M; Gladman, Dafna D; Pullenayegum, Eleanor; Uleryk, Elizabeth; Silverman, Earl D

2014-10-01

Prognosis studies examine outcomes and/or seek to identify predictors or factors associated with outcomes. Many prognostic factors have been identified in systemic lupus erythematosus (SLE), but few have been consistently found across studies. We hypothesized that this is due to a lack of rigor of study designs. This study aimed to systematically assess the methodologic quality of prognosis studies in SLE. A search of prognosis studies in SLE was performed using MEDLINE and Embase, from January 1990 to June 2011. A representative sample of 150 articles was selected using a random number generator and assessed by 2 reviewers. Each study was assessed by a risk of bias tool according to 6 domains: study participation, study attrition, measurement of prognostic factors, measurement of outcomes, measurement/adjustment for confounders, and appropriateness of statistical analysis. Information about missing data was also collected. A cohort design was used in 71% of studies. High risk of bias was found in 65% of studies for confounders, 57% for study participation, 56% for attrition, 36% for statistical analyses, 20% for prognostic factors, and 18% for outcome. Missing covariate or outcome information was present in half of the studies. Only 6 studies discussed reasons for missing data and 2 imputed missing data. Lack of rigorous study design, especially in addressing confounding, study participation and attrition, and inadequately handled missing data, has limited the quality of prognosis studies in SLE. Future prognosis studies should be designed with consideration of these factors to improve methodologic rigor. Copyright © 2014 by the American College of Rheumatology.

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

A Population-Based Study of Gastroesophageal Reflux Disease and Sleep Problems in Elderly Twins

PubMed Central

Lindam, Anna; Jansson, Catarina; Nordenstedt, Helena; Pedersen, Nancy L.; Lagergren, Jesper

2012-01-01

Background & Aims Previous studies indicate an association between sleep problems and gastroesophageal reflux disease (GERD). Although both these conditions separately have moderate heritabilities, confounding by genetic factors has not previously been taken into account. This study aimed to reveal the association between sleep problems and GERD, while adjusting for heredity and other potential confounding factors. Methods This cross-sectional population-based study included all 8,014 same-sexed twins of at least 65 years of age and born in Sweden between 1886 and 1958, who participated in telephone interviews in 1998–2002. Three logistic regression models were used 1) external control analysis, 2) within-pair co-twin analysis with dizygotic (DZ) twin pairs discordant for GERD, and 3) within-pair co-twin analysis with monozygotic (MZ) twin pairs discordant for GERD. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and adjusted for established risk factors for GERD, i.e. sex, age, body mass index (BMI), tobacco smoking, and educational level. Results A dose-response association was identified between increasing levels of sleep problems and GERD in the external control analysis. Individuals who often experienced sleep problems had a two-fold increased occurrence of GERD compared to those who seldom had sleep problems (OR 2.0, 95% CI 1.8–2.4). The corresponding association was of similar strength in the co-twin analysis including 356 DZ pairs (OR 2.2, 95% CI 1.6–3.4), and in the co-twin analysis including 210 MZ pairs (OR 1.5, 95% CI 0.9–2.7). Conclusion A dose-dependent association between sleep problems and GERD remains after taking heredity and other known risk factors for GERD into account. PMID:23119069

Determination of priority among air pollution factors in preventing COPD in residents of Shanghai City proper

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

Xuguang, Tao; Chuan-jie, Hong; Shun-zhang, Yu

The purpose of our study is to determine the priority among ambient sulphur dioxide (SO{sub 2}), inhalable particulates (IP), and indoor use of coal for cooking or heating to prevent COPD in residents of Shanghai city proper. We describe spatial and temporal distribution of the concentration of ambient SO{sub 2}, IP, and the proportion of families who use coal (1980-1985) by the trend surface simulating method and other statistics. Stratified by two sets of extreme levels of ambient SO{sub 2}, IP, and the proportion of coal-using families, we selected eight groups with different combinations of exposure levels. We analyzed themore » relationship between air pollution factors and their health effects at levels of mortality (1978-1987, 232,459 person years), prevalence (1987, 12,037 persons), lung function and local immunologic function (1987, 514 women) with logistic and stepwise regression, and ridit analysis. After controlling for possible confounders, e.g., tobacco smoking and occupational exposure, we found that indoor use of coal is a more important risk factor than ambient SO{sub 2} and IP. We then used canonical correlation analysis to evaluate the overall exposure-effect relationship between one set of air pollution and confounding factors and the other set of health effect indices. High correlation is found between the two. The indoor use of coal is more important for the overall health effects than the ambient SO{sub 2} and IP, to change from coal to gas could reduce the environmental exposure canonical variable more readily, with an effect equivalent to a reduction of 0.1839 mg/m{sup 3} for ambient SO{sub 2}, or 0.2806 mg/m{sup 3} for ambient IP in concentration.« less

Industrial accidents are related to relative body weight: the Israeli CORDIS study.

PubMed Central

Froom, P; Melamed, S; Kristal-Boneh, E; Gofer, D; Ribak, J

1996-01-01

OBJECTIVES: The accident rate might be influenced by intrinsic characteristics of the workers, by risks inherent in the work environment, or a combination of these factors. As increased weight may be associated with sleep disturbances and fatigue, a high body mass index (BMI) might be an independent risk factor for accidents in industrial workers. METHODS: 3801 men were examined and followed up for two years for the occurrence of accidents. The objective environmental conditions were recorded and translated into a single score of ergonomic stress levels. Height and weight were recorded, as were possible confounding factors including measures of fatigue, type A personality, total night time sleep, job satisfaction, somatic complaints, smoking, and education levels. RESULTS: Both BMI and ergonomic stress levels independently predicted involvement in accidents (two or more) with those in the highest BMI quartile who worked in an environment with high ergonomic stress levels having a 4-6 times increased risk of accidents compared with those in the lowest BMI quartile who worked in an environment with low ergonomic stress levels (95% confidence interval (95% CI) 2.4-9.0, P < 0.001). Although increasing somatic complaints and a low educational level also were predictors of accidents, they did not mediate the effect of the BMI on the accident rate. Increasing age, less smoking, and decreased sleep hours were significantly associated with an increased BMI, but the association of BMI and involvement in accidents also could not be explained by those factors or the other confounders. CONCLUSIONS: BMI independently influences the accident rate. Further studies warranted to confirm these findings and to explore mechanisms supporting biological plausibility. PMID:9004929

Robustness of meta-analyses in finding gene × environment interactions

PubMed Central

Shi, Gang; Nehorai, Arye

2017-01-01

Meta-analyses that synthesize statistical evidence across studies have become important analytical tools for genetic studies. Inspired by the success of genome-wide association studies of the genetic main effect, researchers are searching for gene × environment interactions. Confounders are routinely included in the genome-wide gene × environment interaction analysis as covariates; however, this does not control for any confounding effects on the results if covariate × environment interactions are present. We carried out simulation studies to evaluate the robustness to the covariate × environment confounder for meta-regression and joint meta-analysis, which are two commonly used meta-analysis methods for testing the gene × environment interaction or the genetic main effect and interaction jointly. Here we show that meta-regression is robust to the covariate × environment confounder while joint meta-analysis is subject to the confounding effect with inflated type I error rates. Given vast sample sizes employed in genome-wide gene × environment interaction studies, non-significant covariate × environment interactions at the study level could substantially elevate the type I error rate at the consortium level. When covariate × environment confounders are present, type I errors can be controlled in joint meta-analysis by including the covariate × environment terms in the analysis at the study level. Alternatively, meta-regression can be applied, which is robust to potential covariate × environment confounders. PMID:28362796

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

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

PubMed

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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.

Spread of activation and deactivation in the brain: does age matter?

PubMed Central

Gordon, Brian A.; Tse, Chun-Yu; Gratton, Gabriele; Fabiani, Monica

2014-01-01

Cross-sectional aging functional MRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however, may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and region of interest analyses. PMID:25360115

Impact of Differential Attrition on the Association of Education With Cognitive Change Over 20 Years of Follow-up

PubMed Central

Gottesman, Rebecca F.; Rawlings, Andreea M.; Sharrett, A. Richey; Albert, Marilyn; Alonso, Alvaro; Bandeen-Roche, Karen; Coker, Laura H.; Coresh, Josef; Couper, David J.; Griswold, Michael E.; Heiss, Gerardo; Knopman, David S.; Patel, Mehul D.; Penman, Alan D.; Power, Melinda C.; Selnes, Ola A.; Schneider, Andrea L. C.; Wagenknecht, Lynne E.; Windham, B. Gwen; Wruck, Lisa M.; Mosley, Thomas H.

2014-01-01

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48–67 years (1990–1992) through ages 70–89 years (2011–2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors. PMID:24627572

Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study.

PubMed

Gottesman, Rebecca F; Rawlings, Andreea M; Sharrett, A Richey; Albert, Marilyn; Alonso, Alvaro; Bandeen-Roche, Karen; Coker, Laura H; Coresh, Josef; Couper, David J; Griswold, Michael E; Heiss, Gerardo; Knopman, David S; Patel, Mehul D; Penman, Alan D; Power, Melinda C; Selnes, Ola A; Schneider, Andrea L C; Wagenknecht, Lynne E; Windham, B Gwen; Wruck, Lisa M; Mosley, Thomas H

2014-04-15

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.

Not only body weight perception but also body mass index is relevant to suicidal ideation and self-harming behavior in Japanese adolescents.

PubMed

Kinoshita, Kuni; Kinoshita, Yoshihiro; Shimodera, Shinji; Nishida, Atsushi; Inoue, Ken; Watanabe, Norio; Oshima, Norihito; Akechi, Tatsuo; Sasaki, Tsukasa; Inoue, Shimpei; Furukawa, Toshiaki A; Okazaki, Yuji

2012-04-01

Whether a low body mass index (BMI) is directly associated with a high risk of suicidal ideation or self-harming behavior in adolescents is still inconclusive. This study has, therefore, evaluated the relevance of BMI to suicidal ideation and self-harming behavior after controlling for body weight perception (BWP) and other potential confounding factors. BMI, BWP, suicidal ideation, and self-harming behavior were all assessed using a self-report questionnaire administered to 18,104 Japanese adolescents. Potential confounding factors were also evaluated. The data were then analyzed using bivariate and multivariate logistic regression. Low BMI was associated with suicidal ideation and deliberate self-harm when controlling for sex, age, drug use, emotional distress, and BWP. Low BMI may be an independent risk factor for suicidal ideation and deliberate self-harming behavior in Japanese adolescents.

Maternal obesity and childhood wheezing and asthma.

PubMed

Rusconi, Franca; Popovic, Maja

2017-03-01

Obesity represents one of the major public health problems worldwide, with an increased prevalence also among women of reproductive age. Maternal pre-pregnancy overweight and obesity are important risk factors for a number of maternal and foetal/neonatal complications. The objective of this review is to provide an overview of the most recent evidence regarding the associations between pre-pregnancy overweight/obesity and wheezing and asthma in childhood. Potential mechanisms, mediators and confounding factors involved in these associations are also discussed. Despite the relatively large body of studies examining these associations and taking into account main confounders and potential mediators, the causal relationship between maternal obesity and wheezing and asthma in childhood is still uncertain. This uncertainty is not trivial, as any prevention strategy aimed at reducing the burden of these conditions would necessarily imply better understanding of the factors that are in the causal chain. Copyright © 2016. Published by Elsevier Ltd.

Factors Influencing Observed Tillage Impacts on Herbicide Transport

USDA-ARS?s Scientific Manuscript database

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

Betel Nut Usage Is a Major Risk Factor for Coronary Artery Disease

PubMed Central

Khan, Muhammad Shahzeb; Bawany, Faizan Imran; Ahmed, Muhammad Umer; Hussain, Mehwish; Khan, Asadullah; Lashari, Muhammad Nawaz

2014-01-01

Aim: The objective of our study was to assess betel nut usage as one of the major risk factors associated with coronary artery disease. Methods: This case control study consisted of 300 controls and 300 cases. A structured questionnaire was administered to the participants to assess consumption of betel nut and confounding variables. A respondent was considered a regular consumer of betel nut if he/she consumed one or more pieces of betel nut every day for a period of greater than 6 months. Results: About 8 in 10 betel nut chewers developed coronary artery disease. After adjusting for diabetes and hypertension, the odds ratio analysis depicted 7.72 times greater likelihood for coronary artery disease in patients who chewed betel nut for more than 10 years. Conclusion: Our study concludes that betel nut chewing is a significant risk factor leading to the development of coronary artery disease. PMID:24576380

Confounding factors in determining causal soil moisture-precipitation feedback

NASA Astrophysics Data System (ADS)

Tuttle, Samuel E.; Salvucci, Guido D.

2017-07-01

Identification of causal links in the land-atmosphere system is important for construction and testing of land surface and general circulation models. However, the land and atmosphere are highly coupled and linked by a vast number of complex, interdependent processes. Statistical methods, such as Granger causality, can help to identify feedbacks from observational data, independent of the different parameterizations of physical processes and spatiotemporal resolution effects that influence feedbacks in models. However, statistical causal identification methods can easily be misapplied, leading to erroneous conclusions about feedback strength and sign. Here, we discuss three factors that must be accounted for in determination of causal soil moisture-precipitation feedback in observations and model output: seasonal and interannual variability, precipitation persistence, and endogeneity. The effect of neglecting these factors is demonstrated in simulated and observational data. The results show that long-timescale variability and precipitation persistence can have a substantial effect on detected soil moisture-precipitation feedback strength, while endogeneity has a smaller effect that is often masked by measurement error and thus is more likely to be an issue when analyzing model data or highly accurate observational data.

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.

On Estimation of the Survivor Average Causal Effect in Observational Studies when Important Confounders are Missing Due to Death

PubMed Central

Egleston, Brian L.; Scharfstein, Daniel O.; MacKenzie, Ellen

2008-01-01

We focus on estimation of the causal effect of treatment on the functional status of individuals at a fixed point in time t* after they have experienced a catastrophic event, from observational data with the following features: (1) treatment is imposed shortly after the event and is non-randomized, (2) individuals who survive to t* are scheduled to be interviewed, (3) there is interview non-response, (4) individuals who die prior to t* are missing information on pre-event confounders, (5) medical records are abstracted on all individuals to obtain information on post-event, pre-treatment confounding factors. To address the issue of survivor bias, we seek to estimate the survivor average causal effect (SACE), the effect of treatment on functional status among the cohort of individuals who would survive to t* regardless of whether or not assigned to treatment. To estimate this effect from observational data, we need to impose untestable assumptions, which depend on the collection of all confounding factors. Since pre-event information is missing on those who die prior to t*, it is unlikely that these data are missing at random (MAR). We introduce a sensitivity analysis methodology to evaluate the robustness of SACE inferences to deviations from the MAR assumption. We apply our methodology to the evaluation of the effect of trauma center care on vitality outcomes using data from the National Study on Costs and Outcomes of Trauma Care. PMID:18759833

Testing the association between social capital and health over time: a family-based design

PubMed Central

2013-01-01

Background The past decade has seen a vast increase in empirical research investigating associations between social capital and health outcomes. Literature reviews reveal ‘generalized trust’ and ‘social participation’ to be the most robust of the commonly used social capital proxies, both showing positive association with health outcomes. However, this association could be confounded by unmeasured factors, such as the shared environment. Currently, there is a distinct lack of social capital research that takes into account such residual confounding. Methods Using data from the United Kingdom’s British Household Panel Survey (BHPS) (waves thirteen to eighteen, N = 6982), this longitudinal, multilevel study investigates the validity of the association between trust, social participation and self-rated health using a family-based design. As the BHPS samples on entire households, we employed ‘mean’ and ‘difference from the mean’ aggregate measures of social capital, the latter of which is considered a social capital measurement that is not biased by the shared environment of the household. We employed Generalized Estimating Equations for all analyses, our two-level model controlling for correlation at the household level. Results Results show that after adjusting for the shared environment of the household over a six year period, the association between social participation and self-rated health was fully attenuated (OR = 0.97 (95% confidence interval 0.89-1.06)), while the association with trust remained significant (OR = 1.11 (1.02-1.20)). Other health determinants, such as being a smoker, having no formal qualifications and being unemployed maintain their associations with poor self-rated health. Conclusions The association between social capital (specifically trust and social participation) and self-rated health appear to be confounded by shared environmental factors not previously considered by researchers. However, the association with trust remains, adding to existing empirical evidence that generalized trust may be an independent predictor of health. PMID:23866259

Type A personality, hostility, time urgency and unintentional injuries among Chinese undergraduates: a matched case–control study

PubMed Central

2013-01-01

Background Associations between type A behaviour pattern (TABP) and injuries are inconsistent. These inconsistencies may be due to different effects of various components of TABP, namely time urgency/impatience, hostility and competitive drive. It is important to examine the relationship between the global TABP, its two components, and unintentional injuries, among undergraduates in China. Methods On the basis of a previous cross-sectional study, we conducted a matched case–control study. 253 cases and an equal number of age-, gender-, and major-matched controls were included. The questionnaire solicited socio-demographic information, the experience of injuries, the scale of TABP, and other potential confounding factors. Besides the correlation between the global TABP and injuries, the influences of the two components of TABP on injuries were also evaluated. Conditional logistic regression was used to determine the crude odds ratios (ORs) and adjusted ORs of injury events. Results A dose–response relationship was apparent among students who rated themselves higher on the TABP scale (P-value for trend, 0.002), with a crude OR of 2.93 (95% CI: 0.93–9.19) for injuries comparing those with TABP to those with type B behaviour pattern (TBBP). After adjustment for potential confounding factors, TABP remained statistically significant, and the adjusted OR was 5.52 (95% CI: 1.43–21.27); from a comparison of students with TABP to those with TBBP. A dose–response relationship was also apparent between the hostility component and nonfatal injuries, both in crude analysis and after adjusting for other confounders. The relationship between time-hurry and injuries was not statistically significant, based on univariate and multivariate analyses. Conclusions Both the global TABP and the hostility component were associated with a dose response increase in the risk of non-fatal unintentional injuries among Chinese undergraduates. Further studies need to be conducted to confirm or reject this correlation. PMID:24219492

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet in relation to obesity among Iranian female nurses.

PubMed

Barak, Farzaneh; Falahi, Ebrahim; Keshteli, Ammar Hassanzadeh; Yazdannik, Ahmadreza; Esmaillzadeh, Ahmad

2015-03-01

Limited observational studies have considered habitual consumption of the general population to examine the relationship between the Dietary Approaches to Stop Hypertension (DASH) diet and obesity. The aim of the present study was to investigate adherence to the DASH diet in relation to general and central obesity among female nurses in Isfahan, Iran. Cross-sectional study carried out among 293 female nurses aged >30 years who were selected by a multistage, cluster random sampling method. Usual dietary intakes were assessed using a validated FFQ. We constructed the DASH score based on foods and nutrients emphasized or minimized in the DASH diet, focusing on eight components: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products and whole grains and low intakes of sodium, sweetened beverages, and red and processed meats. General and abdominal obesity were defined as BMI ≥ 25 kg/m2 and waist circumference ≥ 88 cm, respectively. Isfahan, Iran. Female nurses (n 293) aged >30 years. Increased adherence to the DASH diet was associated with older age (P<0.01) and lower waist circumference (P=0.04). There was no statistically significant difference in the prevalence of general obesity between extreme quartiles of the DASH diet score. After adjustment for age, energy intake and other confounding factors, DASH diet score was not significantly associated with obesity. However, with further controlling for other dietary factors, those in the highest quartile of DASH diet score were 71 % less likely to have general obesity compared with those in the lowest quartile. In addition, following a DASH diet was inversely associated with central obesity after adjustment for potential confounders (OR=0.37; 95 % CI 0.14, 0.96). We found that adherence to the DASH diet was inversely related to central obesity among Iranian adult females. This association remained significant even after adjustment for potential confounders.

[Factors influencing the measurement of tear film lipid layer thickness with interferometry].

PubMed

Finis, D; Pischel, N; Borrelli, M; Schrader, S; Geerling, G

2014-06-01

The quantitative measurement of the tear film lipid layer thickness is a relatively new and promising method. However, so far it has not been investigated whether there is a diurnal or a day to day variability and whether certain factors are confounding the measurement of the lipid layer thickness. In three different experimental settings, 10 subjects without known sicca syndrome were examined at three different time points on one day, on three different days and before and after therapeutic expression of the Meibomian glands. As a comparison, the parameters tear film break-up time, tear meniscus height, diagnostic expression of the Meibomian glands and subjective symptoms, determined using the OSDI (ocular surface disease index) questionnaire, were measured. The results of the study showed a smaller variation of the lipid layer thickness measurements during the day and from day to day compared to the tear film break-up time. The expression of the Meibomian glands significantly increased the lipid layer thickness. There was a correlation between the baseline values of tear film break-up time and the lipid layer thickness. Our data showed that the lipid layer thickness as measured with the Lipiview® interferometer appears to be a relatively constant parameter over time. In addition, the expression of the Meibomian glands could be identified as a potential confounding factor. In this study we included only healthy subjects without known sicca syndrome. For the future our findings need to be validated in dry eye patients. Georg Thieme Verlag KG Stuttgart · New York.

Association between work-family conflict and musculoskeletal pain among hospital patient care workers

PubMed Central

Kim, Seung-Sup; Okechukwu, Cassandra; Buxton, Orfeu M.; Dennerlein, Jack T.; Boden, Leslie I.; Hashimoto, Dean M.; Sorensen, Glorian

2014-01-01

Background A growing body of evidence suggests that work-family conflict is an important risk factor for workers' health and well-being. The goal of this study is to examine association between work-family conflict and musculoskeletal pain among hospital patient care workers. Methods We analyzed a cross-sectional survey of 1119 hospital patient care workers in 105 units in two urban, academic hospitals. Work-family conflict was measured by 5-item Work-Family Conflict Scale questionnaire. Multilevel logistic regression was applied to examine associations between work-family conflict and self-reported musculoskeletal pain in the past 3 months, adjusting for confounders including work-related psychosocial factors and physical work factors. Results In fully adjusted models, high work-family conflict was strongly associated with neck or shoulder pain (OR: 2.34, 95% CI: 1.64 - 3.34), arm pain (OR: 2.79, 95% CI: 1.64 - 4.75), lower extremity pain (OR: 2.20, 95% CI: 1.54- 3.15) and any musculoskeletal pain (OR: 2.45, 95% CI: 1.56 - 3.85), and a number of body areas in pain (OR: 2.47, 95% CI: 1.82 - 3.36) in the past 3 months. The association with low back pain was attenuated and became non-significant after adjusting for confounders. Conclusions Given the consistent associations between work-family conflict and self-reported musculoskeletal pains, the results suggest that work-family conflict could be an important domain for health promotion and workplace policy development among hospital patient care workers. PMID:23019044

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

PubMed

Elvik, Rune

2011-11-01

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

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma

PubMed Central

Burden, Anne; Roche, Nicolas; Miglio, Cristiana; Hillyer, Elizabeth V; Postma, Dirkje S; Herings, Ron MC; Overbeek, Jetty A; Khalid, Javaria Mona; van Eickels, Daniela; Price, David B

2017-01-01

Background Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre–post historical database study to investigate asthma-related outcomes by treatment. Methods We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Results Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%–100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. Conclusion We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations. PMID:28356782

Twin studies in psychiatry and psychology: science or pseudoscience?

PubMed

Joseph, Jay

2002-01-01

Twin studies are frequently cited in support of the influence of genetic factors for a wide range of psychiatric conditions and psychological trait differences. The most common method, known as the classical twin method, compares the concordance rates or correlations of reared-together identical (MZ) vs. reared-together same-sex fraternal (DZ) twins. However, drawing genetic inferences from MZ-DZ comparisons is problematic due to methodological problems and questionable assumptions. It is argued that the main theoretical assumption of the twin method--known as the "equal environment assumption"--is not tenable. The twin method is therefore of doubtful value as an indicator of genetic influences. Studies of reared-apart twins are discussed, and it is noted that these studies are also vulnerable to methodological problems and environmental confounds. It is concluded that there is little reason to believe that twin studies provide evidence in favor of genetic influences on psychiatric disorders and human behavioral differences.

Is familial risk for depression confounded by individual and familial socioeconomic factors and neighborhood environmental factors? A 7-year follow-up study in Sweden.

PubMed

Hamano, Tsuyoshi; Li, Xinjun; Lönn, Sara Larsson; Nabika, Toru; Sundquist, Jan; Sundquist, Kristina

2018-05-16

Family history of depression is an important risk factor for depression. The aim of this study was to examine whether the effect of family history of depression is confounded by individual and familial socioeconomic factors (i.e., country of origin, educational attainment, family income and mobility) and neighborhood environmental factors (i.e., neighborhood deprivation and neighborhood social capital). The study population comprised 188,907 individuals aged 20-44 years from a nationwide sample of primary care centers in Sweden. Among these individuals, 22,014 with a first event of depression (6,486 men and 15,528 women) were identified during the 7-year follow-up period. Family history of depression was defined as depression in at least one parent. Cross-classified multilevel logistic regression models were used to calculate odds ratios with 95% credible intervals. Increased familial odds were observed after adjustment for individual and familial socioeconomic factors and neighborhood environmental factors for both men and women. Our results suggest that family history of depression is an independent risk factor for depression. Offspring of parents with depression are important targets for disease prevention, regardless of individual and familial socioeconomic factors and neighborhood environmental factors. Copyright © 2018. Published by Elsevier B.V.

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.

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

PubMed

Loeys, Tom; Josephy, Haeike; Dewitte, Marieke

2018-01-01

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

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma.

PubMed

Burden, Anne; Roche, Nicolas; Miglio, Cristiana; Hillyer, Elizabeth V; Postma, Dirkje S; Herings, Ron Mc; Overbeek, Jetty A; Khalid, Javaria Mona; van Eickels, Daniela; Price, David B

2017-01-01

Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre-post historical database study to investigate asthma-related outcomes by treatment. We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%-100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations.

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.

A sibling method for identifying vQTLs

PubMed Central

Domingue, Ben; Dawes, Christopher; Boardman, Jason; Siegal, Mark

2018-01-01

The propensity of a trait to vary within a population may have evolutionary, ecological, or clinical significance. In the present study we deploy sibling models to offer a novel and unbiased way to ascertain loci associated with the extent to which phenotypes vary (variance-controlling quantitative trait loci, or vQTLs). Previous methods for vQTL-mapping either exclude genetically related individuals or treat genetic relatedness among individuals as a complicating factor addressed by adjusting estimates for non-independence in phenotypes. The present method uses genetic relatedness as a tool to obtain unbiased estimates of variance effects rather than as a nuisance. The family-based approach, which utilizes random variation between siblings in minor allele counts at a locus, also allows controls for parental genotype, mean effects, and non-linear (dominance) effects that may spuriously appear to generate variation. Simulations show that the approach performs equally well as two existing methods (squared Z-score and DGLM) in controlling type I error rates when there is no unobserved confounding, and performs significantly better than these methods in the presence of small degrees of confounding. Using height and BMI as empirical applications, we investigate SNPs that alter within-family variation in height and BMI, as well as pathways that appear to be enriched. One significant SNP for BMI variability, in the MAST4 gene, replicated. Pathway analysis revealed one gene set, encoding members of several signaling pathways related to gap junction function, which appears significantly enriched for associations with within-family height variation in both datasets (while not enriched in analysis of mean levels). We recommend approximating laboratory random assignment of genotype using family data and more careful attention to the possible conflation of mean and variance effects. PMID:29617452

Exposure to aircraft and road traffic noise and associations with heart disease and stroke in six European countries: a cross-sectional study

PubMed Central

2013-01-01

Background Although a number of studies have found an association between aircraft noise and hypertension, there is a lack of evidence on associations with other cardiovascular disease. For road traffic noise, more studies are available but the extent of possible confounding by air pollution has not been established. Methods This study used data from the Hypertension and Environmental Noise near Airports (HYENA) study. Cross-sectional associations between self-reported ‘heart disease and stroke’ and aircraft noise and road traffic noise were examined using data collected between 2004 and 2006 on 4712 participants (276 cases), who lived near airports in six European countries (UK, Germany, Netherlands, Sweden, Greece, Italy). Data were available to assess potential confounding by NO2 air pollution in a subsample of three countries (UK, Netherlands, Sweden). Results An association between night-time average aircraft noise and ‘heart disease and stroke’ was found after adjustment for socio-demographic confounders for participants who had lived in the same place for ≥ 20 years (odds ratio (OR): 1.25 (95% confidence interval (CI) 1.03, 1.51) per 10 dB (A)); this association was robust to adjustment for exposure to air pollution in the subsample. 24 hour average road traffic noise exposure was associated with ‘heart disease and stroke’ (OR: 1.19 (95% CI 1.00, 1.41), but adjustment for air pollution in the subsample suggested this may have been due to confounding by air pollution. Statistical assessment (correlations and variance inflation factor) suggested only modest collinearity between noise and NO2 exposures. Conclusions Exposure to aircraft noise over many years may increase risks of heart disease and stroke, although more studies are needed to establish how much the risks associated with road traffic noise may be explained by air pollution. PMID:24131577

Comorbidities confounding the outcomes of surgery for third window syndrome: Outlier analysis

PubMed Central

Mackay‐Promitas, Heather T.; Demirel, Shaban; Gianoli, Gerard J.; Gizzi, Martin S.; Carter, Dale M.; Siker, David A.

2017-01-01

Objective Patients with third window syndrome and superior semicircular canal dehiscence (SSCD) symptoms whose surgical outcomes placed them as outliers were systematically studied to determine comorbidities that were responsible for their poor outcomes due to these confounding factors. Study Design Observational analytic case‐control study in a tertiary referral center. Methods Twelve adult patients with clinical SSCD syndrome underwent surgical management and had outcomes that did not resolve all of their subjective symptoms. In addition to one of the neurotologists, 2 neurologists (one specializing in migraine and the other a neuro‐ophthalmologist), and a psychologist clinician‐investigator completed comprehensive evaluations. Neuropsychology test batteries included: the Millon Behavioral Medicine Diagnostic; Patient Health Questionnaire (PHQ‐9) and Generalized Anxiety Disorder Screener (GAD‐7); Adverse Childhood Experiences Scale; the Wide Range Assessment of Memory and Learning, including the 3 domains of verbal memory, visual memory, and attention/concentration; Wechsler Adult Intelligence Scale; and the Delis‐Kaplan Executive Function System. The control cohort was comprised of 17 participants who previously underwent surgery for third window syndrome that resulted in the expected outcomes of resolution of their third window syndrome symptoms and cognitive dysfunction. Results There was a high rate of psychological comorbidity (n = 6) in the outlier cohort; multiple traumatic brain injuries were also a confounding element (n = 10). One patient had elevated cerebrospinal fluid (CSF) pressure requiring ventriculoperitoneal shunting to control the recurrence of dehiscence and one patient with a drug‐induced Parkinson‐like syndrome and idiopathic progressive neurological degenerative process. Conclusions Components of the Millon Behavioral Medicine Diagnostic, PHQ‐9 and GAD‐7 results suggest that these instruments would be useful as screening tools preoperatively to identify psychological comorbidities that could confound outcomes. The identification of these comorbid psychological as well as other neurological degenerative disease processes led to alternate clinical management pathways for these patients. Level of Evidence 2b. PMID:29094067

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

PubMed

Keogh, Ruth H; Daniel, Rhian M; VanderWeele, Tyler J; Vansteelandt, Stijn

2018-05-01

Estimation of causal effects of time-varying exposures using longitudinal data is a common problem in epidemiology. When there are time-varying confounders, which may include past outcomes, affected by prior exposure, standard regression methods can lead to bias. Methods such as inverse probability weighted estimation of marginal structural models have been developed to address this problem. However, in this paper we show how standard regression methods can be used, even in the presence of time-dependent confounding, to estimate the total effect of an exposure on a subsequent outcome by controlling appropriately for prior exposures, outcomes, and time-varying covariates. We refer to the resulting estimation approach as sequential conditional mean models (SCMMs), which can be fitted using generalized estimating equations. We outline this approach and describe how including propensity score adjustment is advantageous. We compare the causal effects being estimated using SCMMs and marginal structural models, and we compare the two approaches using simulations. SCMMs enable more precise inferences, with greater robustness against model misspecification via propensity score adjustment, and easily accommodate continuous exposures and interactions. A new test for direct effects of past exposures on a subsequent outcome is described.

A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods

PubMed Central

Stürmer, Til; Joshi, Manisha; Glynn, Robert J.; Avorn, Jerry; Rothman, Kenneth J.; Schneeweiss, Sebastian

2006-01-01

Objective Propensity score analyses attempt to control for confounding in non-experimental studies by adjusting for the likelihood that a given patient is exposed. Such analyses have been proposed to address confounding by indication, but there is little empirical evidence that they achieve better control than conventional multivariate outcome modeling. Study design and methods Using PubMed and Science Citation Index, we assessed the use of propensity scores over time and critically evaluated studies published through 2003. Results Use of propensity scores increased from a total of 8 papers before 1998 to 71 in 2003. Most of the 177 published studies abstracted assessed medications (N=60) or surgical interventions (N=51), mainly in cardiology and cardiac surgery (N=90). Whether PS methods or conventional outcome models were used to control for confounding had little effect on results in those studies in which such comparison was possible. Only 9 out of 69 studies (13%) had an effect estimate that differed by more than 20% from that obtained with a conventional outcome model in all PS analyses presented. Conclusions Publication of results based on propensity score methods has increased dramatically, but there is little evidence that these methods yield substantially different estimates compared with conventional multivariable methods. PMID:16632131

Split-plot microarray experiments: issues of design, power and sample size.

PubMed

Tsai, Pi-Wen; Lee, Mei-Ling Ting

2005-01-01

This article focuses on microarray experiments with two or more factors in which treatment combinations of the factors corresponding to the samples paired together onto arrays are not completely random. A main effect of one (or more) factor(s) is confounded with arrays (the experimental blocks). This is called a split-plot microarray experiment. We utilise an analysis of variance (ANOVA) model to assess differentially expressed genes for between-array and within-array comparisons that are generic under a split-plot microarray experiment. Instead of standard t- or F-test statistics that rely on mean square errors of the ANOVA model, we use a robust method, referred to as 'a pooled percentile estimator', to identify genes that are differentially expressed across different treatment conditions. We illustrate the design and analysis of split-plot microarray experiments based on a case application described by Jin et al. A brief discussion of power and sample size for split-plot microarray experiments is also presented.

Testing for gene-environment interaction under exposure misspecification.

PubMed

Sun, Ryan; Carroll, Raymond J; Christiani, David C; Lin, Xihong

2017-11-09

Complex interplay between genetic and environmental factors characterizes the etiology of many diseases. Modeling gene-environment (GxE) interactions is often challenged by the unknown functional form of the environment term in the true data-generating mechanism. We study the impact of misspecification of the environmental exposure effect on inference for the GxE interaction term in linear and logistic regression models. We first examine the asymptotic bias of the GxE interaction regression coefficient, allowing for confounders as well as arbitrary misspecification of the exposure and confounder effects. For linear regression, we show that under gene-environment independence and some confounder-dependent conditions, when the environment effect is misspecified, the regression coefficient of the GxE interaction can be unbiased. However, inference on the GxE interaction is still often incorrect. In logistic regression, we show that the regression coefficient is generally biased if the genetic factor is associated with the outcome directly or indirectly. Further, we show that the standard robust sandwich variance estimator for the GxE interaction does not perform well in practical GxE studies, and we provide an alternative testing procedure that has better finite sample properties. © 2017, The International Biometric Society.

Beyond greening and browning: the need for an integrated understanding of Arctic change

NASA Astrophysics Data System (ADS)

Gamon, J. A.; Huemmrich, K. F.; Hmimina, G.; Yu, R.

2017-12-01

Satellite records and field observations povide contradictory evidence for "greening" or "browning" of Arctic tundra. Large-scale observations of apparent greening have been based on satellite vegetation indices (e.g NDVI). However, a clear interpretation of these trends are confounded by changing snow cover and surface hydrology, both of which influence NDVI and are known to be changing independently of any direct vegetation response. Field studies have demonstrated greening in some areas, but not others, and have also documented changing permafrost depth, surface hydrology and snow cover. Together, these confounding factors can explain some of the contradictory evidence based regarding greening and browning. Given the multiple influences on Arctic NDVI, simple conclusions regarding greening and browning from satellite data alone can be incorrect; when these confounding factors are taken into account, some areas that show apparent greening in the satellite record appear to be undergoing productivity declines due to surface drying. These contradictory interpretations have profound implications for our understanding of changing surface energy balance, biogeochemistry, and surface-atmosphere feedbacks. To better address Arctic ecosystem responses to a changing climate, an integrated, multi-scale, multivariate approach that considers hydrology, permafrost, snow cover and vegetation is needed.

Birth weight and mortality: causality or confounding?

PubMed

Basso, Olga; Wilcox, Allen J; Weinberg, Clarice R

2006-08-15

The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality.

Increased risk of preterm birth in singleton pregnancies after blastocyst versus Day 3 embryo transfer: Canadian ART Register (CARTR) analysis.

PubMed

Dar, S; Librach, C L; Gunby, J; Bissonnette, F; Cowan, L

2013-04-01

Are the fetal outcomes of singleton pregnancies that result from cleavage stage embryo transfer (ET) different from the outcomes from Day 5/6 blastocyst stage ET? There was a significantly higher risk of preterm birth (<37 weeks) in singletons after extended embryo culture (Day 5/6) compared with cleavage stage (Day 3) transfer. Two recent studies, from Sweden and the USA, reported an increased risk of preterm birth in singleton pregnancies after Day 5/6 ET compared with Day 3 ET. The US study also showed increased early preterm births and the Swedish study showed increased fetal malformations in this group. A retrospective cohort study was performed. Data were collected from the Canadian ART Register database for all singleton births after fresh IVF/ICSI ET cycles (2001-2009). A total of 12 712 singleton births were included. Of these, 9506 resulted from a Day 3 ET and 3206 resulted from a blastocyst (Day 5/6) ET. Preterm birth rate <37 weeks (unadjusted by potential confounding factors) was higher with Day 5/6 versus Day 3 transfers (17.2 versus 14.1%, P < 0.001). Using logistic regression analysis to adjust for confounding factors, preterm birth rate <37 weeks was the only outcome significantly increased after Day 5/6 compared with Day 3 transfer (odds ratio 1.32, 95% confidence interval 1.17-1.49). The following confounding factors were adjusted for: year of treatment (2001-2009), maternal age (continuous), parity (0 versus ≥1 birth), diagnosis category, number of oocytes retrieved [≤20 versus >20 (high responder group)], insemination method (IVF versus ICSI), number of embryos transferred (1, 2 or ≥3) and the presence of a vanishing twin (≥1 fetal heart on the initial ultrasonographic examination). Post-natal follow-up studies will be required to determine if this difference we observed translates into adverse long-term effects on these offspring. The rate of early preterm births (<32 weeks) was higher in Day 5/6 versus Day 3, but the low number of cases in this category did not have the power to show a difference (3.0 versus 2.7%, P = 0.34). We found a significantly higher risk of preterm birth (<37 weeks) in singletons after extended embryo culture (Day 5/6) compared with cleavage stage (Day 3) transfer, even when adjusting for confounding factors. Our findings are in agreement with the previous two studies; however, we did not show a difference in the very preterm deliveries (unlike the US study) or in fetal malformations (as in the Swedish study). We hypothesize that there may be a deleterious effect of prolonged in vitro embryo culture on subsequent placentation. Longer term follow-up studies will be required to determine if prolonged in vitro culture to the blastocyst stage has an adverse effect on the long-term health of offspring when compared with shorter cleavage stage culture. None.

Deriving field-based species sensitivity distributions (f-SSDs) from stacked species distribution models (S-SDMs).

PubMed

Schipper, Aafke M; Posthuma, Leo; de Zwart, Dick; Huijbregts, Mark A J

2014-12-16

Quantitative relationships between species richness and single environmental factors, also called species sensitivity distributions (SSDs), are helpful to understand and predict biodiversity patterns, identify environmental management options and set environmental quality standards. However, species richness is typically dependent on a variety of environmental factors, implying that it is not straightforward to quantify SSDs from field monitoring data. Here, we present a novel and flexible approach to solve this, based on the method of stacked species distribution modeling. First, a species distribution model (SDM) is established for each species, describing its probability of occurrence in relation to multiple environmental factors. Next, the predictions of the SDMs are stacked along the gradient of each environmental factor with the remaining environmental factors at fixed levels. By varying those fixed levels, our approach can be used to investigate how field-based SSDs for a given environmental factor change in relation to changing confounding influences, including for example optimal, typical, or extreme environmental conditions. This provides an asset in the evaluation of potential management measures to reach good ecological status.

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

A Genetically Informed Study of Associations between Family Functioning and Child Psychosocial Adjustment

ERIC Educational Resources Information Center

Schermerhorn, Alice C.; D'Onofrio, Brian M.; Turkheimer, Eric; Ganiban, Jody M.; Spotts, Erica L.; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M.

2011-01-01

Research has documented associations between family functioning and offspring psychosocial adjustment, but questions remain regarding whether these associations are partly due to confounding genetic factors and other environmental factors. The current study used a genetically informed approach, the Children of Twins design, to explore the…

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

PubMed

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

2011-12-01

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

A Genetically Informed Study of the Processes Underlying the Association Between Parental Marital Instability and Offspring Adjustment

PubMed Central

D’Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Heath, Andrew C.; Madden, Pamela A.; Slutske, Wendy S.; Martin, Nicholas G.

2010-01-01

Parental divorce is associated with problematic offspring adjustment, but the relation may be due to shared genetic or environmental factors. One way to test for these confounds is to study offspring of twins discordant for divorce. The current analyses used this design to separate the mechanisms responsible for the association between parental divorce, experienced either before or after the age of 16, and offspring well-being. The results were consistent with a causal role of divorce in earlier initiation of sexual intercourse and emotional difficulties, in addition to a greater probability of educational problems, depressed mood, and suicidal ideation. In contrast, the increased risk for cohabitation and earlier initiation of drug use was explained by selection factors, including genetic confounds. PMID:16756440

Association analysis using next-generation sequence data from publicly available control groups: the robust variance score statistic

PubMed Central

Derkach, Andriy; Chiang, Theodore; Gong, Jiafen; Addis, Laura; Dobbins, Sara; Tomlinson, Ian; Houlston, Richard; Pal, Deb K.; Strug, Lisa J.

2014-01-01

Motivation: Sufficiently powered case–control studies with next-generation sequence (NGS) data remain prohibitively expensive for many investigators. If feasible, a more efficient strategy would be to include publicly available sequenced controls. However, these studies can be confounded by differences in sequencing platform; alignment, single nucleotide polymorphism and variant calling algorithms; read depth; and selection thresholds. Assuming one can match cases and controls on the basis of ethnicity and other potential confounding factors, and one has access to the aligned reads in both groups, we investigate the effect of systematic differences in read depth and selection threshold when comparing allele frequencies between cases and controls. We propose a novel likelihood-based method, the robust variance score (RVS), that substitutes genotype calls by their expected values given observed sequence data. Results: We show theoretically that the RVS eliminates read depth bias in the estimation of minor allele frequency. We also demonstrate that, using simulated and real NGS data, the RVS method controls Type I error and has comparable power to the ‘gold standard’ analysis with the true underlying genotypes for both common and rare variants. Availability and implementation: An RVS R script and instructions can be found at strug.research.sickkids.ca, and at https://github.com/strug-lab/RVS. Contact: lisa.strug@utoronto.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24733292

Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

PubMed Central

Kuuranne, Tiia; Saugy, Martial; Baume, Norbert

2014-01-01

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module. PMID:24764553

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

PubMed Central

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

2012-01-01

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

Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

PubMed

Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

2016-06-01

Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors and birth outcomes of anaemia in early pregnancy in a nulliparous cohort.

PubMed

Masukume, Gwinyai; Khashan, Ali S; Kenny, Louise C; Baker, Philip N; Nelson, Gill

2015-01-01

Anaemia in pregnancy is a major public health and economic problem worldwide, that contributes to both maternal and fetal morbidity and mortality. The aim of the study was to calculate the prevalence of anaemia in early pregnancy in a cohort of 'low risk' women participating in a large international multicentre prospective study (n = 5 609), to identify the modifiable risk factors for anaemia in pregnancy in this cohort, and to compare the birth outcomes between pregnancies with and without anaemia in early gestation. The study is an analysis of data that were collected prospectively during the Screening for Pregnancy Endpoints study. Anaemia was defined according to the World Health Organization's definition of anaemia in pregnancy (haemoglobin < 11g/dL). Binary logistic regression with adjustment for potential confounders (country, maternal age, having a marital partner, ethnic origin, years of schooling, and having paid work) was the main method of analysis. The hallmark findings were the low prevalence of anaemia (2.2%), that having no marital partner was an independent risk factor for having anaemia (OR 1.34, 95% CI 1.01-1.78), and that there was no statistically significant effect of anaemia on adverse pregnancy outcomes (small for gestational age, pre-tem birth, mode of delivery, low birth weight, APGAR score < 7 at one and five minutes). Adverse pregnancy outcomes were however more common in those with anaemia than in those without. In this low risk healthy pregnant population we found a low anaemia rate. The absence of a marital partner was a non-modifiable factor, albeit one which may reflect a variety of confounding factors, that should be considered for addition to anaemia's conceptual framework of determinants. Although not statistically significant, clinically, a trend towards a higher risk of adverse pregnancy outcomes was observed in women that were anaemic in early pregnancy.

Parental History of Type 2 Diabetes in Patients with Nonaffective Psychosis

PubMed Central

Fernandez-Egea, Emilio; Miller, Brian; Bernardo, Miguel; Donner, Thomas; Kirkpatrick, Brian

2009-01-01

Introduction We attempted to replicate two previous studies which found an increased risk of diabetes in the relatives of schizophrenia probands. Methods N=34 patients with newly-diagnosed nonaffective psychosis and N=52 non-psychiatric controls were interviewed for parental history of Type 2 diabetes. Results In a logistic regression model that included multiple potential confounders, psychosis was a significant predictor of Type 2 diabetes in either parent (p<0.04). Discussion We found an increased prevalence of Type 2 diabetes in the parents of nonaffective psychosis subjects. This association may be due to shared environmental or genetic risk factors, or both. PMID:18031995

Family structure and risk behaviors: the role of the family meal in assessing likelihood of adolescent risk behaviors.

PubMed

Goldfarb, Samantha; Tarver, Will L; Sen, Bisakha

2014-01-01

Previous literature has asserted that family meals are a key protective factor for certain adolescent risk behaviors. It is suggested that the frequency of eating with the family is associated with better psychological well-being and a lower risk of substance use and delinquency. However, it is unclear whether there is evidence of causal links between family meals and adolescent health-risk behaviors. The purpose of this article is to review the empirical literature on family meals and adolescent health behaviors and outcomes in the US. A SEARCH WAS CONDUCTED IN FOUR ACADEMIC DATABASES: Social Sciences Full Text, Sociological Abstracts, PsycINFO®, and PubMed/MEDLINE. We included studies that quantitatively estimated the relationship between family meals and health-risk behaviors. Data were extracted on study sample, study design, family meal measurement, outcomes, empirical methods, findings, and major issues. Fourteen studies met the inclusion criteria for the review that measured the relationship between frequent family meals and various risk-behavior outcomes. The outcomes considered by most studies were alcohol use (n=10), tobacco use (n=9), and marijuana use (n=6). Other outcomes included sexual activity (n=2); depression, suicidal ideation, and suicide attempts (n=4); violence and delinquency (n=4); school-related issues (n=2); and well-being (n=5). The associations between family meals and the outcomes of interest were most likely to be statistically significant in unadjusted models or models controlling for basic family characteristics. Associations were less likely to be statistically significant when other measures of family connectedness were included. Relatively few analyses used sophisticated empirical techniques available to control for confounders in secondary data. More research is required to establish whether or not the relationship between family dinners and risky adolescent behaviors is an artifact of underlying confounders. We recommend that researchers make more frequent use of sophisticated methods to reduce the problem of confounders in secondary data, and that the scope of adolescent problem behaviors also be further widened.

Thawing as a critical pre-analytical step in the lipidomic profiling of plasma samples: New standardized protocol.

PubMed

Pizarro, Consuelo; Arenzana-Rámila, Irene; Pérez-del-Notario, Nuria; Pérez-Matute, Patricia; González-Sáiz, José María

2016-03-17

Lipid profiling is a promising tool for the discovery and subsequent identification of biomarkers associated with various diseases. However, data quality is quite dependent on the pre-analytical methods employed. To date, potential confounding factors that may affect lipid metabolite levels after the thawing of plasma for biomarker exploration studies have not been thoroughly evaluated. In this study, by means of experimental design methodology, we performed the first in-depth examination of the ways in which thawing conditions affect lipid metabolite levels. After the optimization stage, we concluded that temperature, sample volume and the thawing method were the determining factors that had to be exhaustively controlled in the thawing process to ensure the quality of biomarker discovery. Best thawing conditions were found to be: 4 °C, with 0.25 mL of human plasma and ultrasound (US) thawing. The new US proposed thawing method was quicker than the other methods we studied, allowed more features to be identified and increased the signal of the lipids. In view of its speed, efficiency and detectability, the US thawing method appears to be a simple, economical method for the thawing of plasma samples, which could easily be applied in clinical laboratories before lipid profiling studies. Copyright © 2016 Elsevier B.V. All rights reserved.

The Association Between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Symptoms.

PubMed

van der Meer, Hedwig A; Speksnijder, Caroline M; Engelbert, Raoul H H; Lobbezoo, Frank; Nijhuis-van der Sanden, Maria W G; Visscher, Corine M

2017-09-01

The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. Several subtypes of headaches have been diagnosed: self-reported headache, (probable) migraine, (probable) tension-type headache, and secondary headache attributed to TMD. The presence of TMD was subdivided into 2 subtypes: painful TMD and function-related TMD. The associations between the subtypes of TMD and headaches were evaluated by single regression models. To study the influence of possible confounding factors on this association, the regression models were extended with age, sex, bruxism, stress, depression, and somatic symptoms. Of the included patients (n=203), 67.5% experienced headaches. In the subsample of patients with a painful TMD (n=58), the prevalence of self-reported headaches increased to 82.8%. The associations found between self-reported headache and (1) painful TMD and (2) function-related TMD were confounded by the presence of somatic symptoms. For probable migraine, both somatic symptoms and bruxism confounded the initial association found with painful TMD. The findings of this study imply that there is a central working mechanism overlapping TMD and headache. Health care providers should not regard these disorders separately, but rather look at the bigger picture to appreciate the complex nature of the diagnostic and therapeutic process.

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

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

PubMed Central

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

2016-01-01

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

Towards non-conventional methods of designing register-based epidemiological studies: An application to pediatric research.

PubMed

Gong, Tong; Brew, Bronwyn; Sjölander, Arvid; Almqvist, Catarina

2017-07-01

Various epidemiological designs have been applied to investigate the causes and consequences of fetal growth restriction in register-based observational studies. This review seeks to provide an overview of several conventional designs, including cohort, case-control and more recently applied non-conventional designs such as family-based designs. We also discuss some practical points regarding the application and interpretation of family-based designs. Definitions of each design, the study population, the exposure and the outcome measures are briefly summarised. Examples of study designs are taken from the field of low birth-weight research for illustrative purposes. Also examined are relative advantages and disadvantages of each design in terms of assumptions, potential selection and information bias, confounding and generalisability. Kinship data linkage, statistical models and result interpretation are discussed specific to family-based designs. When all information is retrieved from registers, there is no evident preference of the case-control design over the cohort design to estimate odds ratios. All conventional designs included in the review are prone to bias, particularly due to residual confounding. Family-based designs are able to reduce such bias and strengthen causal inference. In the field of low birth-weight research, family-based designs have been able to confirm a negative association not confounded by genetic or shared environmental factors between low birth weight and the risk of asthma. We conclude that there is a broader need for family-based design in observational research as evidenced by the meaningful contributions to the understanding of the potential causal association between low birth weight and subsequent outcomes.

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

PubMed

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

2015-09-01

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

Resting-state FMRI confounds and cleanup

PubMed Central

Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

2013-01-01

The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

High birth weight and perinatal mortality among siblings: A register based study in Norway, 1967-2011.

PubMed

Kristensen, Petter; Keyes, Katherine M; Susser, Ezra; Corbett, Karina; Mehlum, Ingrid Sivesind; Irgens, Lorentz M

2017-01-01

Perinatal mortality according to birth weight has an inverse J-pattern. Our aim was to estimate the influence of familial factors on this pattern, applying a cohort sibling design. We focused on excess mortality among macrosomic infants (>2 SD above the mean) and hypothesized that the birth weight-mortality association could be explained by confounding shared family factors. We also estimated how the participant's deviation from mean sibling birth weight influenced the association. We included 1 925 929 singletons, born term or post-term to mothers with more than one delivery 1967-2011 registered in the Medical Birth Registry of Norway. We examined z-score birth weight and perinatal mortality in random-effects and sibling fixed-effects logistic regression models including measured confounders (e.g. maternal diabetes) as well as unmeasured shared family confounders (through fixed effects models). Birth weight-specific mortality showed an inverse J-pattern, being lowest (2.0 per 1000) at reference weight (z-score +1 to +2) and increasing for higher weights. Mortality in the highest weight category was 15-fold higher than reference. This pattern changed little in multivariable models. Deviance from mean sibling birth weight modified the mortality pattern across the birth weight spectrum: small and medium-sized infants had increased mortality when being smaller than their siblings, and large-sized infants had an increased risk when outweighing their siblings. Maternal diabetes and birth weight acted in a synergistic fashion with mortality among macrosomic infants in diabetic pregnancies in excess of what would be expected for additive effects. The inverse J-pattern between birth weight and mortality is not explained by measured confounders or unmeasured shared family factors. Infants are at particularly high mortality risk when their birth weight deviates substantially from their siblings. Sensitivity analysis suggests that characteristics related to maternal diabetes could be important in explaining the increased mortality among macrosomic infants.

Learning Effective Connectivity Network Structure from fMRI Data Based on Artificial Immune Algorithm

PubMed Central

Ji, Junzhong; Liu, Jinduo; Liang, Peipeng; Zhang, Aidong

2016-01-01

Many approaches have been designed to extract brain effective connectivity from functional magnetic resonance imaging (fMRI) data. However, few of them can effectively identify the connectivity network structure due to different defects. In this paper, a new algorithm is developed to infer the effective connectivity between different brain regions by combining artificial immune algorithm (AIA) with the Bayes net method, named as AIAEC. In the proposed algorithm, a brain effective connectivity network is mapped onto an antibody, and four immune operators are employed to perform the optimization process of antibodies, including clonal selection operator, crossover operator, mutation operator and suppression operator, and finally gets an antibody with the highest K2 score as the solution. AIAEC is then tested on Smith’s simulated datasets, and the effect of the different factors on AIAEC is evaluated, including the node number, session length, as well as the other potential confounding factors of the blood oxygen level dependent (BOLD) signal. It was revealed that, as contrast to other existing methods, AIAEC got the best performance on the majority of the datasets. It was also found that AIAEC could attain a relative better solution under the influence of many factors, although AIAEC was differently affected by the aforementioned factors. AIAEC is thus demonstrated to be an effective method for detecting the brain effective connectivity. PMID:27045295

Correction for Metastability in the Quantification of PID in Thin-film Module Testing: Preprint

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

Hacke, Peter L; Johnston, Steven; Spataru, Sergiu

A fundamental change in the analysis for the accelerated stress testing of thin-film modules is proposed, whereby power changes due to metastability and other effects that may occur due to the thermal history are removed from the power measurement that we obtain as a function of the applied stress factor. The power of reference modules normalized to an initial state - undergoing the same thermal and light- exposure history but without the applied stress factor such as humidity or voltage bias - is subtracted from that of the stressed modules. For better understanding and appropriate application in standardized tests, themore » method is demonstrated and discussed for potential-induced degradation testing in view of the parallel-occurring but unrelated physical mechanisms that can lead to confounding power changes in the module.« less

Incidence of Infectious Mononucleosis in Universities and U.S. Military Settings

PubMed Central

Williams-Harmon, Yolonda J; Jason, Leonard A; Katz, Ben Z.

2016-01-01

Objective The reported incidence rates for Infectious Mononucleosis (IM) within universities and military settings vary widely from study to study. Several factors may have contributed to the discrepancy in these incidence rates include misdiagnosis, ambiguity in the reported sample populations, and number of students who visited and were diagnosed at their campus's health service centers. The current review examines previously reported literature on the incidence rate in universities and military settings of infectious mononucleosis taking into account these possible confounding factors. Methods Articles examined for the literature review were selected by searching several databases within Google Scholar and PubMed. Results Variance in the incidence rates could be due to differences in the populations studied, true geographic or epidemiologic variation or inconsistent number of students who visited and were diagnosed at their campus's health service centers. PMID:27583306

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

PubMed Central

Wyss, Richard; Hansen, Ben B.; Ellis, Alan R.; Gagne, Joshua J.; Desai, Rishi J.; Glynn, Robert J.; Stürmer, Til

2017-01-01

Abstract A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the “dry-run” analysis, which divides the unexposed population into “pseudo-exposed” and “pseudo-unexposed” groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models. PMID:28338910

External adjustment sensitivity analysis for unmeasured confounding: an application to coronary stent outcomes, Pennsylvania 2004-2008.

PubMed

Huesch, Marco D

2013-06-01

Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004-2005 followed up for death through 3 years. Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. © Health Research and Educational Trust.

Does caregiving cause psychological distress? The case for familial and genetic vulnerabilities in female twins.

PubMed

Vitaliano, Peter P; Strachan, Eric; Dansie, Elizabeth; Goldberg, Jack; Buchwald, Dedra

2014-04-01

Informal caregiving can be deleterious to mental health, but research results are inconsistent and may reflect an interaction between caregiving and vulnerability to stress. We examined psychological distress among 1,228 female caregiving and non-caregiving twins. By examining monozygotic and dizygotic twin pairs discordant for caregiving, we assessed the extent to which distress is directly related to caregiving or confounded by common genes and environmental exposures. Caregiving was associated with distress as measured by mental health functioning, anxiety, perceived stress, and depression. The overall association between caregiving and distress was confounded by common genes and environment for mental health functioning, anxiety, and depression. Common environment also confounded the association of caregiving and perceived stress. Vulnerability to distress is a factor in predicting caregivers' psychosocial functioning. Additional research is needed to explicate the mechanisms by which common genes and environment increase the risk of distress among informal caregivers.

Indoor biofuel air pollution and respiratory health: the role of confounding factors among women in highland Guatemala.

PubMed

Bruce, N; Neufeld, L; Boy, E; West, C

1998-06-01

A number of studies have reported associations between indoor biofuel air pollution in developing countries and chronic obstructive lung disease (COLD) in adults and acute lower respiratory infection (ALRI) in children. Most of these studies have used indirect measures of exposure and generally dealt inadequately with confounding. More reliable, quantified information about this presumed effect is an important pre-requisite for prevention, not least because of the technical, economic and cultural barriers to achieving substantial exposure reductions in the world's poorest households, where ambient pollution levels are typically between ten and a hundred times higher than recommended standards. This study was carried out as part of a programme of research designed to inform the development of intervention studies capable of providing quantified estimates of health benefits. The association between respiratory symptoms and the use of open fires and chimney woodstoves ('planchas'), and the distribution of confounding factors, were examined in a cross-sectional study of 340 women aged 15-45 years, living in a poor rural area in the western highlands of Guatemala. The prevalence of reported cough and phlegm was significantly higher for three of six symptom measures among women using open fires. Although this finding is consistent with a number of other studies, none has systematically examined the extent to which strong associations with confounding variables in these settings limit the ability of observational studies to define the effect of indoor air pollution adequately. Very strong associations (P < 0.0001) were found between the type of fire and a number of household and socioeconomic factors including the arrangement of rooms, floor type, and possession of a radio and television. The spouse's economic activity type was also significantly associated (P < 0.05). Thus, while 82% of open fire users had dirt floors and only 18% cement or tile floors, the situation was reversed for plancha users, only 16% of whom had dirt floors. Confounding presents a substantial problem for observational studies of indoor air pollution and health, although there is a reasonable case for believing that the observed association is causal. Intervention studies are required for stronger evidence of this association, and more importantly, to determine the size of health benefit achievable through feasible exposure reductions.

Assisted Reproductive Technology and Risk for Autism Spectrum Disorder

ERIC Educational Resources Information Center

Zachor, Ditza A.; Itzchak, E. Ben

2011-01-01

Epidemiologic studies on maternal and pregnancy risk factors for autism spectrum disorder (ASD), including use of assisted reproductive technology (ART), found conflicting results. This study included the following aims: to assess frequencies of ART in a large ASD group; to examine confounding birth and familial risk factors in the ASD with ART…

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…

Child Migration and Academic Performance: The Case of Basic Education in Ghana

ERIC Educational Resources Information Center

Tamanja, Emmanuel Makabu J.

2016-01-01

The nexus between migration and academic performance is complex and difficult to extricate. Not only are there several factors affecting academic performance, but also many of these factors are confounding, making it difficult to identify and isolate in order to address. Furthermore, the discourse appears silent on the nexus between child…

Assay dilution factors confound measures of total antioxidant capacity in polyphenol-rich juices

USDA-ARS?s Scientific Manuscript database

The extent to which sample dilution factor (DF) affects Total Antioxidant Capacity (TAC) values is poorly understood. Thus, we examined the impact of DF on the ORAC, FRAP, DPPH, and Total Phenols (TP) assays using pomegranate juice (PJ), grape juice (GJ), selected flavonoids, ascorbic acid, and ella...

Associations among Obesity, Eating Speed, and Oral Health

PubMed Central

Sonoda, Chikanobu; Fukuda, Hideki; Kitamura, Masayasu; Hayashida, Hideaki; Kawashita, Yumiko; Furugen, Reiko; Koyama, Zenya; Saito, Toshiyuki

2018-01-01

Objective This study was conducted to understand how eating speed and oral health condition are associated with obesity in Japanese working men. Methods We studied a total of 863 men attending an annual medical checkup of the Japanese Maritime Self Defense Force in Sasebo City, Japan. Participants answered a questionnaire about their eating speed, and we examined their anthropometric status in terms of BMI, waist circumference, and oral health condition, especially periodontal disease and number of functional teeth. Multivariate logistic regression analyses adjusting for potential confounding variables were performed. Results The multivariate-adjusted odds ratio for waist circumference greater than 90 cm of the ‘very fast’ group compared to the ‘slow, very slow’ group was 5.22 (95% confidence interval 1.81–15.06) after adjusting for potential confounding factors. Individuals were more likely to have waist circumference greater than 90 cm if they had a larger ‘number of missing functional teeth’ (odds ratio 1.14; 95% confidence interval 1.01–1.28) and severe periodontal disease (odds ratio 2.74; 95% confidence interval, 1.46–5.13). Conclusion Eating speed, the number of missing functional teeth, and severe periodontal disease are associated independently with larger waist circumference. PMID:29669358

The health consequences of maquiladora work: women on the US-Mexican border.

PubMed Central

Guendelman, S; Silberg, M J

1993-01-01

OBJECTIVES. As more US companies take jobs to Mexico, complaints are growing that the assembly plants (maquiladoras) exert adverse effects on workers' health. This study assessed the health of female electronic and garment maquiladora workers, comparing them with women employed in services and non-wage earners. METHODS. A survey was administered to 480 women living in Tijuana in 1990. The sample was stratified by occupation and length of employment. Functional impediments, nervousness, depression, and sense of control were used as outcome variables, controlling for other confounders. RESULTS. Despite working longer hours, receiving lower wages, and having less decision latitude and education, maquiladora workers were not worse off than service workers. Maquiladora workers reported similar incidences of depression and lack of control over life. Electronics workers, especially, had lower incidences of nervousness and functional impediments, after controlling for other confounders. Also, maquiladora work did not add an extra health burden compared with non-wage earners. CONCLUSIONS. The adverse effects of maquiladoras previously reported may have been exaggerated. Subjective factors, including negative attitudes toward economic adversity and work dissatisfaction, were stronger predictors of health than were objective indicators. PMID:8417604

Diabetes Mellitus is Associated With Low Secretion Rates of Immunoglobulin A in Saliva

PubMed Central

Oikawa, Junko; Ukawa, Shigekazu; Ohira, Hideki; Kawamura, Takashi; Wakai, Kenji; Ando, Masahiko; Hata, Akira; Tamakoshi, Akiko

2015-01-01

Background The association between diabetes mellitus (DM) and low secretory immunoglobulin A (s-IgA) secretion rates is one mechanism suspected of influencing susceptibility to infections among DM patients. However, several studies have shown contradictory results. We examined these two factors to seek evidence of an association among older people. Methods We analyzed a prospective cohort of 2306 subjects (1209 men and 1097 women) around 64 years old from the New Integrated Suburban Seniority Investigation (NISSIN) Project in Nisshin, Japan. DM statuses were ascertained from levels of fasting plasma glucose and HbA1c, and s-IgA secretion rates were obtained from 5-min saliva samples. We used an analysis of covariance adjusted for possible confounders to compare s-IgA secretion rates according to DM status. Results s-IgA secretion rates in DM participants were lower than in those classified as normal (18.6 µg/min vs 15.0 µg/min, P = 0.03), even after elimination of the effects of possible confounders. Conclusions DM was associated with lower s-IgA secretion rates. This suggests that lower s-IgA levels may be a mechanism of susceptibility to infection in individuals with DM. PMID:26094794

Religion and mortality among the community-dwelling elderly.

PubMed Central

Oman, D; Reed, D

1998-01-01

OBJECTIVES: This study analyzed the prospective association between attending religious services and all-cause mortality to determine whether the association is explainable by 6 confounding factors: demographics, health status, physical functioning, health habits, social functioning and support, and psychological state. METHODS: The association between self-reported religious attendance and subsequent mortality over 5 years for 1931 older residents of Marin County, California, was examined by proportional hazards regression. Interaction terms of religion with social support were used to explore whether other forms of social support could substitute for religion and diminish its protective effect. RESULTS: Persons who attended religious services had lower mortality than those who did not (age- and sex-adjusted relative hazard [RH] = 0.64; 95% confidence interval [CI] = 0.52, 0.78). Multivariate adjustment reduced this relationship only slightly (RH = 0.76; 95% CI = 0.62, 0.94), primarily by including physical functioning and social support. Contrary to hypothesis, religious attendance tended to be slightly more protective for those with high social support. CONCLUSIONS: Lower mortality rates for those who attend religious services are only partly explained by the 6 possible confounders listed above. Psychodynamic and other explanations need further investigation. PMID:9772846

Suicidal Ideation and Mental Distress Among Adults With Military Service History: Results From 5 US States, 2010

PubMed Central

Gordon, Adam J.; Bossarte, Robert M.

2014-01-01

Objectives. We examined the association of military service history with past-year suicidal ideation and past-30-days mental distress in a probability-based sample of adults. Methods. We gathered 2010 Behavioral Risk Factor Surveillance System data from 5 states that asked about past-year suicidal ideation. Military service was defined as current or former active-duty service or National Guard or Reserves service. We stratified analyses into 18 to 39 years, 40 to 64 years, and 65 years and older age groups and used multiple logistic regression analyses, adjusted for demographic confounders, to discern the association of military service history with past-year suicidal ideation and past-30-days mental distress. Results. Among the 26 736 respondents, 13.1% indicated military service history. After adjusting for several confounders, we found military history status among those aged 40 to 64 years was associated with both past-year suicidal ideation and past-30-days mental distress. We found no significant associations among the younger or older age groups. Conclusions. Differences in suicidal ideation between military and nonmilitary individuals may occur in midlife. Future research should examine the possibility of cohort effects, service era effects, or both. PMID:25100426

Track and Field Practice and Bone Outcomes among Adolescents: A Pilot Study (ABCD-Growth Study)

PubMed Central

Faustino-da-Silva, Yuri da Silva Ventura; Werneck, André Oliveira; Maillane-Vanegas, Santiago; Lynch, Kyle Robinson; Exupério, Isabella Neto; Ito, Igor Hideki; Fernandes, Romulo Araújo

2018-01-01

Background Osteoporosis is considered a public health problem with high worldwide prevalence. One approach to prevention is through the promotion of physical activity, especially exercise, during adolescence. Methods This study compared bone variables in different body segments in adolescents according to participation in track and field. The study included 34 adolescents (22 boys), of whom 17 were track and field athletes and 17 were control subjects. Bone mineral density (BMD, g/cm2) and bone mineral content (BMC, g) were analyzed using dual energy X-ray absorptiometry (total body stratified by body segments). Peak height velocity was used to estimate somatic maturation. Results Athletes had higher BMD (P=0.003) and BMC (P=0.011) values in the lower limbs and higher whole body BMD (P=0.025) than the control group. However, when adjusted for confounding factors, the difference was not maintained. The groups had similar lean soft tissue values (P=0.094). Training overload was positively correlated with BMD in the upper limbs (r=0.504; 95% confidence interval, 0.031-0.793). Although track and field athletes had higher BMD and BMC values in the lower limbs, these differences were not significant when adjusted for confounding factors. Conclusions Track and field participation in adolescence appears to influence BMD and BMC in lower limbs, and fat-free mass seems to mediate this effect. Also, higher training loads were found to be positive for bone health in upper limbs. PMID:29564304

Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

PubMed

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-03-09

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

PubMed Central

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-01-01

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phenotypes” that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. PMID:25758824

Can We Train Machine Learning Methods to Outperform the High-dimensional Propensity Score Algorithm?

PubMed

Karim, Mohammad Ehsanul; Pang, Menglan; Platt, Robert W

2018-03-01

The use of retrospective health care claims datasets is frequently criticized for the lack of complete information on potential confounders. Utilizing patient's health status-related information from claims datasets as surrogates or proxies for mismeasured and unobserved confounders, the high-dimensional propensity score algorithm enables us to reduce bias. Using a previously published cohort study of postmyocardial infarction statin use (1998-2012), we compare the performance of the algorithm with a number of popular machine learning approaches for confounder selection in high-dimensional covariate spaces: random forest, least absolute shrinkage and selection operator, and elastic net. Our results suggest that, when the data analysis is done with epidemiologic principles in mind, machine learning methods perform as well as the high-dimensional propensity score algorithm. Using a plasmode framework that mimicked the empirical data, we also showed that a hybrid of machine learning and high-dimensional propensity score algorithms generally perform slightly better than both in terms of mean squared error, when a bias-based analysis is used.

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

PubMed

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

2017-04-01

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

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.

Flooding and Mental Health: A Systematic Mapping Review

PubMed Central

Fernandez, Ana; Black, John; Jones, Mairwen; Wilson, Leigh; Salvador-Carulla, Luis; Astell-Burt, Thomas; Black, Deborah

2015-01-01

Background Floods are the most common type of global natural disaster. Floods have a negative impact on mental health. Comprehensive evaluation and review of the literature are lacking. Objective To systematically map and review available scientific evidence on mental health impacts of floods caused by extended periods of heavy rain in river catchments. Methods We performed a systematic mapping review of published scientific literature in five languages for mixed studies on floods and mental health. PUBMED and Web of Science were searched to identify all relevant articles from 1994 to May 2014 (no restrictions). Results The electronic search strategy identified 1331 potentially relevant papers. Finally, 83 papers met the inclusion criteria. Four broad areas are identified: i) the main mental health disorders—post-traumatic stress disorder, depression and anxiety; ii] the factors associated with mental health among those affected by floods; iii) the narratives associated with flooding, which focuses on the long-term impacts of flooding on mental health as a consequence of the secondary stressors; and iv) the management actions identified. The quantitative and qualitative studies have consistent findings. However, very few studies have used mixed methods to quantify the size of the mental health burden as well as exploration of in-depth narratives. Methodological limitations include control of potential confounders and short-term follow up. Limitations Floods following extreme events were excluded from our review. Conclusions Although the level of exposure to floods has been systematically associated with mental health problems, the paucity of longitudinal studies and lack of confounding controls precludes strong conclusions. Implications We recommend that future research in this area include mixed-method studies that are purposefully designed, using more rigorous methods. Studies should also focus on vulnerable groups and include analyses of policy and practical responses. PMID:25860572

Association Between Fruit and Vegetable Consumption and Sleep Quantity in Pregnant Women.

PubMed

Duke, C H; Williamson, J A; Snook, K R; Finch, K C; Sullivan, K L

2017-05-01

Introduction To determine the association of fruit and vegetable consumption with overall sleep duration among pregnant women. Methods Data from the 2011 and 2012 Behavioral Risk Factors Surveillance System (BRFSS) were used. All women (n = 2951) of childbearing age (18-44 years) who were pregnant and responded to all fruit and vegetable consumption and sleep duration questions were included. Covariates included age, race, education level, exercise, and marital status. Data were analyzed using linear and ordinal logistic regression. Results Total daily fruit and vegetable consumption was not associated with sleep duration among pregnant women, controlling for confounders [β = -0.03, (-0.07, 0.00)]. Orange and green vegetable consumption were both inversely associated with sleep duration [β = -0.19, (-0.38, -0.01) and β = -0.20, (-0.33, -0.08) respectively]. Ordinal logistic regression found that the odds of meeting or exceeding sleep time recommendations increased slightly with each unit increase in total fruit and vegetable consumption [OR = 1.05 (1.003, 1.092)] and for every unit increase in fruit consumption [OR = 1.12 (1.038, 1.208)]. Women who exercised within the past 30 days reported approximately 20 min of additional sleep compared to those who did not [β = 0.32 (0.16, 0.49)]. Age, employment status, and marital status were also independently associated with sleep duration. Discussion Sleep duration in pregnant women was associated with exercise and other demographic factors, but only mildly associated with fruit and vegetable consumption. Future research should investigate the effects of additional factors including sleep quality, gestational age, family status and other medications as potential confounders.

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System

PubMed Central

2012-01-01

Background While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair. Methods A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors. Results Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis. Conclusions Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not. PMID:22257790

Association between angiotensin II type 1 receptor gene polymorphism and essential hypertension: the Ohasama Study.

PubMed

Sugimoto, Ken; Katsuya, Tomohiro; Ohkubo, Takayoshi; Hozawa, Atsushi; Yamamoto, Koichi; Matsuo, Akiko; Rakugi, Hiromi; Tsuji, Ichiro; Imai, Yutaka; Ogihara, Toshio

2004-08-01

Gene targeting approaches have suggested that the angiotensin II type 1 receptor (AT1R) is involved in blood pressure (BP) regulation and modulation of the effect of angiotensin II. The A1166C polymorphism of the AT1 receptor gene (AT1R/A1166C) is associated with hypertension in Caucasians, but not in Japanese. The goal of this study, the Ohasama Study, was to examine the association between AT1R/A1166C and hypertension, especially home BP, in the Japanese general population. The Ohasama Study was a cohort study based on Japanese rural residents of Ohasama Town in the northern part of Japan. Subjects who gave informed consent to the study protocol and genetic analysis were recruited. Home BP was measured twice in the morning within 1 h of waking up and in the evening just before going to bed. The TaqMan polimerase chain reaction (PCR) method clearly determined AT1R/A1166C genotypes (n =1,207). The genotype distribution of AT1R/A1166C was as follows: AA 84%; AC 15%; CC 1%. There was almost no difference in baseline characteristics among the AT1R genotypes (AA, AC, CC). In the subjects not receiving antihypertensive medication (n =817), both casual BP and home BP were not different among the AT1R genotypes after adjusting for confounding factors (age, sex, body mass index, current smoking habit and current alcohol consumption). The frequency of hypertension showed no difference among AT1R genotypes after adjusting for confounding factors, though the AC and CC genotypes were more frequent in hypertensives than in normotensives. Our data suggested that the AT1R/A1166C polymorphism is not a major genetic predisposing factor for hypertension in Japanese.

The Relationship between Intake of Dairy Products and Polycystic Ovary Syndrome in Women Who Referred to Isfahan University of Medical Science Clinics in 2013

PubMed Central

Rajaeieh, Golnaz; Marasi, Mohamadreza; Shahshahan, Zahra; Hassanbeigi, Fatemmeh; Safavi, Seied Morteza

2014-01-01

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive women. Nearly 10% of young women in this period involved. Although factors such as Insulin Resistance, hyper insulinemia, obesity and dietary are suggested to be associated with PCOS, cause of PCOS is not completely understood. Dairy products (a key component of the usual diet) of participants can also affect the factors of this disease and may have beneficial effects on treatment of PCOS. However, research in this area is scarce. The purpose of this study was to evaluate the relationship between dairy products consumption and PCOS. Methods: This descriptive cross-sectional study of 400 women was conducted in Shahid Beheshti Hospital of Isfahan University of Medical Science, Iran. Dietary intake was evaluated by validated food frequency questionnaire. Other variables such as ovarian disease, inherited predisposition, age at menarche, physical activity and history of other diseases were evaluated using questionnaire. Data analysis was performed by a logistic regression test using SPSS software version 15 Predictive analytics software and solutions. Results: There were a significant association between PCOS and ovarian disease (P < 0.001), age (P < 0.001) and using medication (P = 0.001). Body mass index (BMI) was inversely associated with PCOS, but it was not significant (P = 0.068). There was a significant direct relationship between milk consumption and risk of PCOS after adjusting for confounding factors (P = 0.028). Conclusions: The findings of this study indicated that ovarian disease and medication use is directly linked to PCOS. Dairy consumption was not significantly correlated with PCOS. However, after adjustment for confounders, there was an direct relationship between milk consumption and risk of PCOS. PMID:25013687

Paternal education status significantly influences infants’ measles vaccination uptake, independent of maternal education status

PubMed Central

2012-01-01

Background Despite increased funding of measles vaccination programs by national governments and international aid agencies, structural factors encumber attainment of childhood measles immunisation to levels which may guarantee herd immunity. One of such factors is parental education status. Research on the links between parental education and vaccination has typically focused on the influence of maternal education status. This study aims to demonstrate the independent influence of paternal education status on measles immunisation. Methods Comparable nationally representative survey data were obtained from six countries with the highest numbers of children missing the measles vaccine in 2008. Logistic regression analysis was applied to examine the influence of paternal education on uptake of the first dose of measles vaccination, independent of maternal education, whilst controlling for confounding factors such as respondent’s age, urban/rural residence, province/state of residence, religion, wealth and occupation. Results The results of the analysis show that even if a mother is illiterate, having a father with an education of Secondary (high school) schooling and above is statistically significant and positively correlated with the likelihood of a child being vaccinated for measles, in the six countries analysed. Paternal education of secondary or higher level was significantly and independently correlated with measles immunisation uptake after controlling for all potential confounders. Conclusions The influence of paternal education status on measles immunisation uptake was investigated and found to be statistically significant in six nations with the biggest gaps in measles immunisation coverage in 2008. This study underscores the imperative of utilising both maternal and paternal education as screening variables to identify children at risk of missing measles vaccination prospectively. PMID:22568861

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

PubMed

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

2010-05-01

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

Parental mental health, childhood psychiatric disorders, and asthma attacks in island Puerto Rican youth.

PubMed

Ortega, Alexander N; Goodwin, Renee D; McQuaid, Elizabeth L; Canino, Glorisa

2004-01-01

Previous research documents an association of poor parental mental health with asthma in children. This study aims to determine whether the associations between parental mental health problems and childhood asthma attacks persist after controlling for childhood anxiety and depression and other confounding factors. A community household sample of youth ages 4 to 17 years and their primary caregivers from the US Commonwealth of Puerto Rico was studied to determine the associations between parental mental health and childhood asthma attacks. Regression models that predicted asthma attacks in youth controlled for parental mental health problems, childhood anxiety and depression, zone of residence, and parents' age, education, and perception of poverty. After adjusting for children's depressive and anxiety disorders as well as other important confounders, associations between parental depression, suicide attempts, ataque de nervios, and history of mental health treatment and asthma attacks in offspring, by parental report, persisted. Additionally, the frequency of parental mental health problems was associated with children's asthma attacks. Parents with mental health problems were more likely to report histories of asthma attacks in their children compared with parents without mental health problems in Puerto Rico. These associations were not attributable to internalizing disorders in youth but persisted independent of childhood psychopathology and other confounding factors. Clinicians and researchers should recognize the relations between poor parental mental health and childhood asthma and explore the potential role of family psychosocial and behavioral factors related to the manifestation of the disease.

The effects of sleep duration on the incidence of cardiovascular events among middle-aged male workers in Japan.

PubMed

Hamazaki, Yuko; Morikawa, Yuko; Nakamura, Koshi; Sakurai, Masaru; Miura, Katsuyuki; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki

2011-09-01

Although previous epidemiological studies have investigated the relationship between sleep duration and various cardiovascular events, the results have been inconsistent. Accordingly, we conducted a follow-up survey to investigate the relationship between sleep duration and cardiovascular events among male workers, accounting for occupational factors that might confound the true relationship. A total of 2282 male employees aged 35-54 years based in a factory in Japan were followed for 14 years. The risk of cardiovascular events was compared among 4 groups stratified based on sleep duration at baseline (<6, 6-6.9, 7-7.9, and ≥8 hours). Cardiovascular events included stroke, coronary events and sudden cardiac death. The hazard ratios for events were calculated using a Cox proportional hazards model, with the 7-7.9-hour group serving as a reference. The model was adjusted for potential confounders including traditional cardiovascular risk factors and working characteristics. During 14 years of follow-up, 64 cardiovascular events were recorded including 30 strokes, 27 coronary events and 7 sudden cardiac deaths. After adjustment for possible confounders, the hazard ratios for cardiovascular and coronary events in the <6-hour group were 3.49 [95% confidence interval (95% CI) 1.30-9.40] and 4.95 (95% CI 1.31-18.73), respectively. There was no significant increment in the risk of stroke for any sleep duration groups. Short sleep duration (<6 hours) was a significant risk factor for coronary events in a Japanese male working population.

Hospitalizations for Accidents and Induries in the U.S. Navy. IV. A Comparison of Nuclear and Conventionally Powered Surface Ships.

DTIC Science & Technology

1986-04-01

SURFACE SHIPS C. M. BONE J . C. HELMKAMP DTIC REPORT NO. 86-8 IWELECTE "’AUG 2 71986 ~. DistributLlU hti~ NAVAL HEALTH RESEARCH CENTER Q... P.O. BOX 85122...carrier and cruiser personnel comparisons. This risk was 1.5 and 2. J times the risk of hospitalization, respectively, for the same aged personnel...in these two groups, some confounding bias may have occurred. 10 Pr,, ’e ’, j .*-~~’V**, *~*~**** ,’*. ’~ Another confounding factor may stem from duty

The development of a modified spectral ripple test.

PubMed

Aronoff, Justin M; Landsberger, David M

2013-08-01

Poor spectral resolution can be a limiting factor for hearing impaired listeners, particularly for complex listening tasks such as speech understanding in noise. Spectral ripple tests are commonly used to measure spectral resolution, but these tests contain a number of potential confounds that can make interpretation of the results difficult. To measure spectral resolution while avoiding those confounds, a modified spectral ripple test with dynamically changing ripples was created, referred to as the spectral-temporally modulated ripple test (SMRT). This paper describes the SMRT and provides evidence that it is sensitive to changes in spectral resolution.

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.

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

PubMed

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

2008-09-01

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

Educational inequality in cardiovascular diseases: a sibling approach.

PubMed

Søndergaard, Grethe; Dalton, Susanne Oksbjerg; Mortensen, Laust Hvas; Osler, Merete

2018-02-01

Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases, ischaemic heart disease and stroke, respectively, were explained by family factors shared by siblings. The study population included all individuals born in Denmark between 1950 and 1979 who had at least one full sibling born in the same period. Using Cox regression, data were analysed in conventional cohort and within-sibship analyses in which the association was examined within siblings discordant on education. Assuming that attenuation of associations in the within-sibship as compared with the cohort analyses would indicate confounding from factors shared within families. A lower educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate of ischaemic heart disease among women less than 45 years who had a primary school education was 94% (hazard ratio 1.94 (1.78-2.12) higher than among those with a vocational education, while it attenuated to 51% (hazard ratio 1.51 (1.34-1.71)) in the within-sibship analysis. Confounding from factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart disease and stroke.

Relationships among fitness, obesity, screen time and academic achievement in Japanese adolescents.

PubMed

Morita, Noriteru; Nakajima, Toshihiro; Okita, Koichi; Ishihara, Toru; Sagawa, Masato; Yamatsu, Koji

2016-09-01

Students who study intensively in one of Japan's 'cram schools' and/or spend excess time on electronic devices such as video games are in a sedentary state much of the time, and this may affect their physical fitness. We investigated whether there are relationships among obesity, physical fitness and academic achievement in Japanese students after controlling for socioeconomic and behavioral confounding factors. The data of 315 students (152 females [48%], 163 males [52%]; 12-13yrs old) were analyzed. Academic achievement was assessed by the total grade points on eight school subjects (GP8). Students with a body mass index at or above the 85th percentile of each gender were classified as the overweight/obese group. Physical fitness was evaluated by the total score on eight fitness tests. Socioeconomic and behavioral confounders including the mother's educational background, household income, cram school utilization and time spent on video games/mobile phones were used as covariates. The GP8 of the overweight/obese students was significantly lower than that of the normal weight students (27.2 vs. 29.0 points, respectively). After adjusting for the confounders, the physical fitness score was found to be a significant factor for determinants of GP8 in boys (β=0.324), but not in girls. The obesity status was a factor for GP8 in the girls (β=-0.160) but not in the boys. These results suggest that physical fitness in boys and obesity status in girls could be important factors not only for health status but also for academic achievement, independent of socioeconomic and behavioral backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Instrumental variable methods in comparative safety and effectiveness research.

PubMed

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

2010-06-01

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

Is cannabis a risk factor for suicide attempts in men and women with psychotic illness?

PubMed

Waterreus, A; Di Prinzio, P; Badcock, J C; Martin-Iverson, M; Jablensky, A; Morgan, V A

2018-05-16

To investigate whether recent cannabis use by men and women with psychotic disorders was associated with increased risk of suicide attempt, and to determine associated factors, stratified by sex. Data from 1065 men and 725 women interviewed in the Australian national survey of psychosis were analysed to model separately, for each sex, the impact of daily, casual or no past-year cannabis use and other risk factors including age, on a past-year suicide attempt. In the past year, 168 (9.4%) participants attempted suicide. Unadjusted analyses showed daily cannabis users of both sexes had significantly increased odds of attempting suicide compared to non-users. After adjusting for confounding factors, this relationship was no longer significant. Depression had the strongest association with attempting suicide for both sexes. Sex differences in other risk factors were observed. In post hoc analysis, daily cannabis use was associated with higher odds of attempting suicide in older men compared to non-users; this was not found in younger men or women. Associations between past-year cannabis use and suicide attempts were confounded by other factors (depression, loneliness, homelessness and hallucinations). The possibility of greater risk of suicidal behaviour with regular cannabis use for older men should be considered.

Coronary Artery Calcification in Japanese Men in Japan and Hawaii

PubMed Central

Abbott, Robert D.; Ueshima, Hirotsugu; Rodriguez, Beatriz L.; Kadowaki, Takashi; Masaki, Kamal H.; Willcox, Bradley J.; Sekikawa, Akira; Kuller, Lewis H.; Edmundowicz, Daniel; Shin, Chol; Kashiwagi, Atsunori; Nakamura, Yasuyuki; El-Saed, Aiman; Okamura, Tomonori; White, Roger; Curb, J. David

2013-01-01

Explanations for the low prevalence of atherosclerosis in Japan versus United States are often confounded with genetic variation. To help remove such confounding, coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was compared between Japanese men in Japan and Japanese men in Hawaii. Findings are based on risk factor and CAC measurements that were made from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40 to 50 years and without cardiovascular disease. After age-adjustment, there was a 3-fold excess in the odds of prevalent CAC scores ≥10 in Hawaii versus Japan (relative odds [RO] = 3.2; 95% confidence interval [CI] = 2.1,4.9). While men in Hawaii had a generally poorer risk factor profile, men in Japan were 4-times more likely to smoke cigarettes (49.5 vs. 12.7%, p<0.001). In spite of marked risk factor differences between the samples, none of the risk factors provided an explanation for the low amounts of CAC in Japan. After risk factor adjustment, the RO of CAC scores ≥10 in Hawaii versus Japan was 4.0 (95% CI = 2.2,7.4). Further studies are needed to identify factors that offer protection against atherosclerosis in Japanese men in Japan. PMID:17728270

The non-evaluative circumplex of personality adjectives.

PubMed

Saucier, G; Ostendorf, F; Peabody, D

2001-08-01

In judgments about personality, descriptive and evaluative aspects are ordinarily combined; separating them can be important both theoretically and practically. Study 1 showed that two similar descriptive factors can be found in analyses of personality terms, selected independently in English and in German and using different methods to control for evaluation. The factors relate to two pairs of independent axes suggested by previous work: Assertive-Unassertive and Tight-Loose, or alternatively, Interactional Orientation (Extraversion-Introversion) and Affective Orientation. These two pairs of axes are shown to be rotations of each other, and to form the prime non-evaluative circumplex. As in previous studies, non-evaluative scales elicited higher levels of self-peer agreement than did more typical evaluation-confounded scales. Study 2 showed that adjective scales for the octants of this circumplex have circular ordering, can fit even very stringent constraints of a circumplex model, have mild to strong isomorphism with the interpersonal circumplex, but represent somewhat broader constructs, and are systematically related to the Big Five and the Big Three personality factors.

Intra-dialytic hypertension is associated with high mortality in hemodialysis patients

PubMed Central

Yoon, Kyu Tae; Gil, Hyo Wook; Hong, Sae Yong

2017-01-01

Background Intra-dialytic hypertension (IDH) is emerging as an important issue in hemodialysis patients. Its risk factors and clinical outcomes are unclear. Methods A total of 73 prevalent hemodialysis patients were enrolled. They included 14 (19.2%) patients with baseline IDH and 59 patients without IDH. Their clinical parameters, laboratory parameters, and mortality were investigated over 78 months. Results The risks factor of IDH included low serum potassium levels, low ultrafiltration, and low arm muscle area. Lower median survival was evident in the IDH group compared to the non-IDH group, but was not significantly different. After adjusting for relevant confounders for age, the IDH group displayed 2.846 times higher mortality rate than the non-IDH Group (adjusted hazard ratio: 2.846; 95% confidence interval: 1.081–7.490; P = 0.034). Conclusion IDH is associated with high mortality in hemodialysis patients. Clinicians should be aware of the risk factors. Future research studies are needed to explore the mechanisms involved in the association between IDH and mortality. PMID:28742805

Smoking and Physical Activity in Healthy Adults: A Cross-Sectional Study in Tehran

PubMed Central

Heydari, Gholamreza; Yousefifard, Mahmoud; Asady, Hadi; Baikpour, Masoud; Barat, Atena

2015-01-01

Background: Smoking and physical inactivity are two major risk factors for non-communicable diseases (NCDs). Not only these factors have a causal effect on NCDs, but they can also affect each other. This study aimed to assess the relationship between these factors as well as their effect on NCDs. Materials and Methods: A total of 2,602 healthy adults aged 30–60 years participated in this survey in 2010. Data on demographic characteristics, medical history, smoking status, physical activity and anthropometric measures including weight and height were collected and analyzed. The effect of smoking on physical activity was evaluated by logistic regression adjusting for potential confounders. Results: Among demographic characteristics, only age (P<0.001) and educational level (P<0.001) had a significant association with smoking status. Compared with nonsmokers, smokers had an odds ratio of 4.88 (95% CI, 3.34–7.13) for having unsatisfactory physical activity. Conclusion: The present study showed that cigarette smoking negatively affects the quality of physical activity. PMID:27114725

Associations of Cannabis and Cigarette Use with Depression and Anxiety at Age 18: Findings from the Avon Longitudinal Study of Parents and Children

PubMed Central

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

2015-01-01

Introduction Substance use is associated with common mental health disorders, but the causal effect of specific substances is uncertain. We investigate whether adolescent cannabis and cigarette use is associated with incident depression and anxiety, while attempting to account for confounding and reverse causation. Methods We used data from ALSPAC, a UK birth cohort study, to investigate associations between cannabis or cigarettes (measured at age 16) and depression or anxiety (measured at age 18), before and after adjustment for pre-birth, childhood and adolescent confounders. Our imputed sample size was 4561 participants. Results Both cannabis (unadjusted OR 1.50, 95% CI 1.26, 1.80) and cigarette use (OR 1.37, 95% CI 1.16, 1.61) increased the odds of developing depression. Adjustment for pre-birth and childhood confounders partly attenuated these relationships though strong evidence of association persisted for cannabis use. There was weak evidence of association for cannabis (fully adjusted OR 1.30, 95% CI 0.98, 1.72) and insufficient evidence for association for cigarette use (fully adjusted OR = 0.97, 95% CI 0.75, 1.24) after mutually adjusting for each other, or for alcohol or other substance use. Neither cannabis nor cigarette use were associated with anxiety after adjustment for pre-birth and childhood confounders. Conclusions Whilst evidence of association between cannabis use and depression persisted after adjusting for pre-term and childhood confounders, our results highlight the difficulties in trying to estimate and interpret independent effects of cannabis and tobacco on psychopathology. Complementary methods are required to robustly examine effects of cannabis and tobacco on psychopathology. PMID:25875443

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

PubMed

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

2017-11-22

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

Gang membership and substance use: guilt as a gendered causal pathway

PubMed Central

Coffman, Donna L.; Melde, Chris; Esbensen, Finn-Aage

2014-01-01

Objectives We examine whether anticipated guilt for substance use is a gendered mechanism underlying the noted enhancement effect of gang membership on illegal drug use. We also demonstrate a method for making stronger causal inferences when assessing mediation in the presence of moderation and time-varying confounding. Methods We estimate a series of inverse propensity weighted models to obtain unbiased estimates of mediation in the presence of confounding of the exposure (i.e., gang membership) and mediator (i.e., anticipated guilt) using three waves of data from a multi-site panel study of a law-related education program for youth (N=1,113). Results The onset of gang membership significantly decreased anticipated substance use guilt among both male and female respondents. This reduction was significantly associated with increased frequency of substance use only for female respondents, however, suggesting that gender moderates the mechanism through which gang membership influences substance use. Conclusions Criminologists are often concerned with identifying causal pathways for antisocial and/or delinquent behavior, but confounders of the exposure, mediator, and outcome often interfere with efforts to assess mediation. Many new approaches have been proposed for strengthening causal inference for mediation effects. After controlling for confounding using inverse propensity weighting, our results suggest that interventions aimed at reducing substance use by current and former female gang members should focus on the normative aspects of these behaviors. PMID:26190954

Segmentation of Vasculature from Fluorescently Labeled Endothelial Cells in Multi-Photon Microscopy Images.

PubMed

Bates, Russell; Irving, Benjamin; Markelc, Bostjan; Kaeppler, Jakob; Brown, Graham; Muschel, Ruth J; Brady, Sir Michael; Grau, Vicente; Schnabel, Julia A

2017-08-09

Vasculature is known to be of key biological significance, especially in the study of tumors. As such, considerable effort has been focused on the automated segmentation of vasculature in medical and pre-clinical images. The majority of vascular segmentation methods focus on bloodpool labeling methods, however, particularly in the study of tumors it is of particular interest to be able to visualize both perfused and non-perfused vasculature. Imaging vasculature by highlighting the endothelium provides a way to separate the morphology of vasculature from the potentially confounding factor of perfusion. Here we present a method for the segmentation of tumor vasculature in 3D fluorescence microscopy images using signals from the endothelial and surrounding cells. We show that our method can provide complete and semantically meaningful segmentations of complex vasculature using a supervoxel-Markov Random Field approach. We show that in terms of extracting meaningful segmentations of the vasculature, our method out-performs both a state-ofthe- art method, specific to these data, as well as more classical vasculature segmentation methods.

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

PubMed Central

Zeka, Ariana; Melly, Steve J; Schwartz, Joel

2008-01-01

Background Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors. Methods A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes (birth weight, small for gestational age and preterm births), in a two-level hierarchical model. Results We found effects of both individual (education, race, prenatal care index) and area-based (median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income. Conclusion Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health. PMID:19032747

Association analysis using next-generation sequence data from publicly available control groups: the robust variance score statistic.

PubMed

Derkach, Andriy; Chiang, Theodore; Gong, Jiafen; Addis, Laura; Dobbins, Sara; Tomlinson, Ian; Houlston, Richard; Pal, Deb K; Strug, Lisa J

2014-08-01

Sufficiently powered case-control studies with next-generation sequence (NGS) data remain prohibitively expensive for many investigators. If feasible, a more efficient strategy would be to include publicly available sequenced controls. However, these studies can be confounded by differences in sequencing platform; alignment, single nucleotide polymorphism and variant calling algorithms; read depth; and selection thresholds. Assuming one can match cases and controls on the basis of ethnicity and other potential confounding factors, and one has access to the aligned reads in both groups, we investigate the effect of systematic differences in read depth and selection threshold when comparing allele frequencies between cases and controls. We propose a novel likelihood-based method, the robust variance score (RVS), that substitutes genotype calls by their expected values given observed sequence data. We show theoretically that the RVS eliminates read depth bias in the estimation of minor allele frequency. We also demonstrate that, using simulated and real NGS data, the RVS method controls Type I error and has comparable power to the 'gold standard' analysis with the true underlying genotypes for both common and rare variants. An RVS R script and instructions can be found at strug.research.sickkids.ca, and at https://github.com/strug-lab/RVS. lisa.strug@utoronto.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationships of colorectal cancer with dietary factors and public health indicators: an ecological study.

PubMed

Abbastabar, Hedayat; Roustazadeh, Abazar; Alizadeh, Ali; Hamidifard, Parvin; Valipour, Mehrdad; Valipour, Ali Asghar

2015-01-01

Colorectal cancer (CRC) is the third most common cancer in Iranian women and fifth in men. The aims of this study were to investigate the relation of dietary factors and public health indicators to its development. The required information (2001-2006) about risk factors was obtained from the Non- Communicable Disease Surveillance Centre (NCDSC) of Iran. Risk factor data (RFD) from 89,404 individuals (15-64 years old) were gathered by questionnaire and laboratory examinations through a cross sectional study in all provinces by systematic clustering sampling method. CRC incidence segregated by age and gender was obtained from Cancer Registry Ministry of Health (CRMH) of Iran. First, correlation coefficients were used for data analysis and then multiple regression analysis was performed to control for confounding factors. Colorectal cancer incidence showed a positive relationship with diabetes mellitus, hypertension, lacking or low physical activity, high education, high intake of dairy products, and non-consumption of vegetables and fruits. We concluded that many dietary factors and public health indicators have positive relationships with CRC and might therefore be targets of preliminary prevention. However, since this is an ecological study limited by potential ecological fallacy the results must be interpreted with caution.

The effect of relationship status on health with dynamic health and persistent relationships.

PubMed

Kohn, Jennifer L; Averett, Susan L

2014-07-01

The dynamic evolution of health and persistent relationship status pose econometric challenges to disentangling the causal effect of relationships on health from the selection effect of health on relationship choice. Using a new econometric strategy we find that marriage is not universally better for health. Rather, cohabitation benefits the health of men and women over 45, being never married is no worse for health, and only divorce marginally harms the health of younger men. We find strong evidence that unobservable health-related factors can confound estimates. Our method can be applied to other research questions with dynamic dependent and multivariate endogenous variables. Copyright © 2014 Elsevier B.V. All rights reserved.

The use of aquatic bioconcentration factors in ecological risk assessments: Confounding issues, laboratory v/s modeled results

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

Brandt, C.; Blanton, M.L.; Dirkes, R.

1995-12-31

Bioconcentration in aquatic systems is generally taken to refer to contaminant uptake through non-ingestion pathways (i.e., dermal and respiration uptake). Ecological risk assessments performed on aquatic systems often rely on published data on bioconcentration factors to calibrate models of exposure. However, many published BCFs, especially those from in situ studies, are confounded by uptake from ingestion of prey. As part of exposure assessment and risk analysis of the Columbia River`s Hanford Reach, the authors tested a methodology to estimate radionuclide BCFs for several aquatic species in the Hanford Reach of the Columbia River. The iterative methodology solves for BCFs frommore » known body burdens and environmental media concentrations. This paper provides BCF methodology description comparisons of BCF from literature and modeled values and how they were used in the exposure assessment and risk analysis of the Columbia River`s Hanford Reach.« less

A Vision for an International Multi-Sensor Snow Observing Mission

NASA Technical Reports Server (NTRS)

Kim, Edward

2015-01-01

Discussions within the international snow remote sensing community over the past two years have led to encouraging consensus regarding the broad outlines of a dedicated snow observing mission. The primary consensus - that since no single sensor type is satisfactory across all snow types and across all confounding factors, a multi-sensor approach is required - naturally leads to questions about the exact mix of sensors, required accuracies, and so on. In short, the natural next step is to collect such multi-sensor snow observations (with detailed ground truth) to enable trade studies of various possible mission concepts. Such trade studies must assess the strengths and limitations of heritage as well as newer measurement techniques with an eye toward natural sensitivity to desired parameters such as snow depth and/or snow water equivalent (SWE) in spite of confounding factors like clouds, lack of solar illumination, forest cover, and topography, measurement accuracy, temporal and spatial coverage, technological maturity, and cost.

Why Assembling Plant Genome Sequences Is So Challenging

PubMed Central

Claros, Manuel Gonzalo; Bautista, Rocío; Guerrero-Fernández, Darío; Benzerki, Hicham; Seoane, Pedro; Fernández-Pozo, Noé

2012-01-01

In spite of the biological and economic importance of plants, relatively few plant species have been sequenced. Only the genome sequence of plants with relatively small genomes, most of them angiosperms, in particular eudicots, has been determined. The arrival of next-generation sequencing technologies has allowed the rapid and efficient development of new genomic resources for non-model or orphan plant species. But the sequencing pace of plants is far from that of animals and microorganisms. This review focuses on the typical challenges of plant genomes that can explain why plant genomics is less developed than animal genomics. Explanations about the impact of some confounding factors emerging from the nature of plant genomes are given. As a result of these challenges and confounding factors, the correct assembly and annotation of plant genomes is hindered, genome drafts are produced, and advances in plant genomics are delayed. PMID:24832233

Posttraumatic Stress Disorder, Cardiovascular and Metabolic Disease: A Review of the Evidence

PubMed Central

Dedert, Eric A.; Calhoun, Patrick S.; Watkins, Lana L.; Sherwood, Andrew; Beckham, Jean C.

2011-01-01

Background Posttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease. Purpose The purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes. Methods A systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted. Results The literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers. Conclusions Although the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research. PMID:20174903

Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men

PubMed Central

De Roos, A J; Zahm, S; Cantor, K; Weisenburger, D; Holmes, F; Burmeister, L; Blair, A

2003-01-01

Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these "potentially carcinogenic" pesticides suggested a positive trend of risk with exposure to increasing numbers. Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios. PMID:12937207

Nonadherence in dialysis patients: prevalence, measurement, outcome, and psychological determinants.

PubMed

Clark, Sarah; Farrington, Ken; Chilcot, Joseph

2014-01-01

Nonadherence to aspects of the management of End-Stage Kidney Disease (ESKD) is common. Estimates of nonadherence vary with assessment method. Whilst readily available and free from report bias, physiological proxies-frequently used as measures of adherence-are often confounded by clinical factors including residual kidney function and dialysis adequacy. Despite variation in estimates of its prevalence, it is clear that suboptimal adherence to dialysis prescriptions, medication and diet can lead to adverse clinical outcomes. Several factors can help explain nonadherence in ESKD including mood, self-efficacy, social support, illness, and treatment perceptions. Psychological interventions have been shown to improve ESKD adherence, yet achieving long-term behavior change remains challenging. Identifying individuals who struggle to adhere to aspects of the dialysis regime, and tailoring theory-led interventions to improve and support adherence is a clear clinical need requiring further empirical enquiry. © 2013 Wiley Periodicals, Inc.

Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST)

PubMed Central

Pressman, Alice; Avins, Andrew L.; Neuhaus, John; Ackerson, Lynn; Rudd, Peter

2012-01-01

Background Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality. Aims Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality. Methods Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication over the entire course of each individual’s participation in the study, while those with “lower placebo adherence” took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables. Results Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR = 0.61, 95% Confidence Interval: 0.46–0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations. Conclusions Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation. PMID:22265975

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations.

PubMed

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2017-01-01

To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors.

PubMed

Bernhard, Felix P; Heinzel, Sebastian; Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Bochud, Murielle; Guessous, Idris; Paccaud, Fred; Burnier, Michel; Wuerzner, Gregoire

2016-04-01

Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.

Psychosocial working conditions, occupational groups, and risk of disability pension due to mental diagnoses: a cohort study of 43,000 Swedish twins.

PubMed

Samuelsson, Åsa; Ropponen, Annina; Alexanderson, Kristina; Svedberg, Pia

2013-07-01

The aim of this study was to investigate associations between psychosocial working conditions, occupational groups defined by sector, and disability pension (DP) with mental diagnoses while accounting for familial confounding. A prospective population-based cohort study was conducted, including all Swedish twins who, in January 1993, were living and working in Sweden and not on old-age pension or DP (N=42 715). The twins were followed from 1993-2008 regarding DP. Data on DP, exposures, and covariates were obtained from national registries. Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (95% CI) were constructed for the whole cohort, and for discordant twin pairs. The associations for the whole cohort between DP with mental diagnoses and (i) job demands (HR 1.23, 95% CI 1.06-1.43), (ii) job control (HR 0.91, 95% CI 0.83-0.99), (iii) healthcare and social work (HR 1.41, 95% CI 1.04-1.92), and (iv) service and military work (HR 2.07, 95% CI 1.37-3.14) remained after accounting for possible confounders, including familial factors, while the associations between DP and (i) social support, (ii) type of jobs, and (iii) some of the occupational groups were attenuated, becoming non-significant. In the discordant twin pair analyses, commercial work was significantly associated with lower risk of DP (HR 0.55, 95% CI 0.32-0.95). One unit increase in job demands and working in the occupational groups healthcare and social work or service and military work seem to be risk factors of DP with mental diagnoses, independent from various background factors including familial ones. However, one unit increase in job control or working in commercial work seem to be protective factors of such DP, accounting for confounding factors of this study.

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.

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

PubMed

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

2016-06-03

Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Occupational exposure and ovarian cancer risk.

PubMed

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

2014-07-01

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

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

Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Risk of Adverse Pregnancy Outcomes among Women Practicing Poor Sanitation in Rural India: A Population-Based Prospective Cohort Study

PubMed Central

Padhi, Bijaya K.; Baker, Kelly K.; Dutta, Ambarish; Cumming, Oliver; Freeman, Matthew C.; Satpathy, Radhanatha; Das, Bhabani S.; Panigrahi, Pinaki

2015-01-01

Background The importance of maternal sanitation behaviour during pregnancy for birth outcomes remains unclear. Poor sanitation practices can promote infection and induce stress during pregnancy and may contribute to adverse pregnancy outcomes (APOs). We aimed to assess whether poor sanitation practices were associated with increased risk of APOs such as preterm birth and low birth weight in a population-based study in rural India. Methods and Findings A prospective cohort of pregnant women (n = 670) in their first trimester of pregnancy was enrolled and followed until birth. Socio-demographic, clinical, and anthropometric factors, along with access to toilets and sanitation practices, were recorded at enrolment (12th week of gestation). A trained community health volunteer conducted home visits to ensure retention in the study and learn about study outcomes during the course of pregnancy. Unadjusted odds ratios (ORs) and adjusted odds ratios (AORs) and 95% confidence intervals for APOs were estimated by logistic regression models. Of the 667 women who were retained at the end of the study, 58.2% practiced open defecation and 25.7% experienced APOs, including 130 (19.4%) preterm births, 95 (14.2%) births with low birth weight, 11 (1.7%) spontaneous abortions, and six (0.9%) stillbirths. Unadjusted ORs for APOs (OR: 2.53; 95% CI: 1.72–3.71), preterm birth (OR: 2.36; 95% CI: 1.54–3.62), and low birth weight (OR: 2.00; 95% CI: 1.24–3.23) were found to be significantly associated with open defecation practices. After adjustment for potential confounders such as maternal socio-demographic and clinical factors, open defecation was still significantly associated with increased odds of APOs (AOR: 2.38; 95% CI: 1.49–3.80) and preterm birth (AOR: 2.22; 95% CI: 1.29–3.79) but not low birth weight (AOR: 1.61; 95% CI: 0.94–2.73). The association between APOs and open defecation was independent of poverty and caste. Even though we accounted for several key confounding factors in our estimates, the possibility of residual confounding should not be ruled out. We did not identify specific exposure pathways that led to the outcomes. Conclusions This study provides the first evidence, to our knowledge, that poor sanitation is associated with a higher risk of APOs. Additional studies are required to elucidate the socio-behavioural and/or biological basis of this association so that appropriate targeted interventions might be designed to support improved birth outcomes in vulnerable populations. While it is intuitive to expect that caste and poverty are associated with poor sanitation practice driving APOs, and we cannot rule out additional confounders, our results demonstrate that the association of poor sanitation practices (open defecation) with these outcomes is independent of poverty. Our results support the need to assess the mechanisms, both biological and behavioural, by which limited access to improved sanitation leads to APOs. PMID:26151447

Effectiveness of electronic stability control on single-vehicle accidents.

PubMed

Lyckegaard, Allan; Hels, Tove; Bernhoft, Inger Marie

2015-01-01

This study aims at evaluating the effectiveness of electronic stability control (ESC) on single-vehicle injury accidents while controlling for a number of confounders influencing the accident risk. Using police-registered injury accidents from 2004 to 2011 in Denmark with cars manufactured in the period 1998 to 2011 and the principle of induced exposure, 2 measures of the effectiveness of ESC were calculated: The crude odds ratio and the adjusted odds ratio, the latter by means of logistic regression. The logistic regression controlled for a number of confounding factors, of which the following were significant. For the driver: Age, gender, driving experience, valid driving license, and seat belt use. For the vehicle: Year of registration, weight, and ESC. For the accident surroundings: Visibility, light, and location. Finally, for the road: Speed limit, surface, and section characteristics. The present study calculated the crude odds ratio for ESC-equipped cars of getting in a single-vehicle injury accident as 0.40 (95% confidence interval [CI], 0.34-0.47) and the adjusted odds ratio as 0.69 (95% CI, 0.54-0.88). No difference was found in the effectiveness of ESC across the injury severity categories (slight, severe, and fatal). In line with previous results, this study concludes that ESC reduces the risk for single-vehicle injury accidents by 31% when controlling for various confounding factors related to the driver, the car, and the accident surroundings. Furthermore, it is concluded that it is important to control for human factors (at a minimum age and gender) in analyses where evaluations of this type are performed.

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

Approaches for Strengthening Causal Inference Regarding Prenatal Risk Factors for Childhood Behavioural and Psychiatric Disorders

ERIC Educational Resources Information Center

Lewis, Sarah J.; Relton, Caroline; Zammit, Stanley; Smith, George Davey

2013-01-01

Background: The risk of childhood behavioural and psychiatric diseases could be substantially reduced if modifiable risk factors for these disorders were identified. The critical period for many of these exposures is likely to be in utero as this is the time when brain development is most rapid. However, due to confounding and other limitations of…

Unraveling the Effect of Genes and Environment in the Transmission of Parental Antisocial Behavior to Children's Conduct Disturbance, Depression and Hyperactivity

ERIC Educational Resources Information Center

Silberg, Judy L.; Maes, Hermine; Eaves, Lindon J.

2012-01-01

Background: A critical issue in devising effective interventions for the treatment of children's behavioral and emotional problems identifying genuine family environmental factors that place children at risk. In most twin and family studies, environmental factors are confounded with both direct genetic risk from parents and the indirect effect of…

Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions.

PubMed

Nishtala, P S; Chyou, T-Y

2017-04-01

Prescription sequence symmetry analyses (PSSA) is a ubiquitous tool employed in pharmacoepidemiological research to predict adverse drug reactions (ADRs). Several studies have reported the advantage of PSSA as a method that can be applied to a large prescription database with computational ease. The objective of this study was to validate New Zealand (NZ) prescription database as a potential source for identifying ADRs using the PSSA method. We analysed de-identified individual-level prescription data for people aged 65 years and above for the period 2005 to 2014 from the pharmaceutical collections supplied by the NZ Ministry of Health. We selected six positive controls that have been previously investigated and reported for causing ADRs. The six positive controls identified were amiodarone (repeated twice), frusemide, simvastatin, lithium and fluticasone. Amiodarone and lithium have been reported to induce thyroid dysfunction. Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis. Thyroxine was identified as a marker drug to treat hypothyroidism associated with amiodarone and lithium. Carbimazole was identified as a marker drug to treat hyperthyroidism associated with amiodarone use. Quinine sulphate was identified as a marker drug to treat muscle cramps associated with statins. In addition, we also analysed six negative controls that are unlikely to be associated with ADRs. The main outcome measure is to determine associations with ADRs using adjusted sequence ratios (ASR), and 95% confidence intervals RESULTS AND DISCUSSION: Our analyses confirmed a significant signal for all six positive controls. Significant positive associations were noted for amiodarone [ASR = 3·57, 95% CI (3·17-4·02)], and lithium chloride induced hypothyroidism [ASR = 3·43, 95% CI (2·55-4·70)]. Amiodarone was also strongly associated with hyperthyroidism [ASR = 8·81 95% CI (5·86-13·77)]. Simvastatin was associated with muscle cramps [ASR = 1·69, 95% CI (1·61-1·77)]. Fluticasone was positively associated with oral candidiasis [ASR = 2·34, 95% CI (2·19-2·50)]. Frusemide was associated with hypokalaemia [ASR = 2·94, 95% CI (2·83-3·05]). No strong associations were noted for the negative pairs. It is important to highlight that PSSA automatically controls for all confounding factors including unknown and unmeasured confounding variables, plus the effect of temporal trend in prescriptions, and hence allows a more robust ADR detection especially when confounding factors are difficult to determine or measure. New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse. © 2016 John Wiley & Sons Ltd.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

PubMed

Kjøllesdal, M K R; Ariansen, I; Mortensen, L H; Davey Smith, G; Næss, Ø

2016-12-01

To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

WHAT TO DO IF THERE IS NO REFERENCE SYSTEM

EPA Science Inventory

Efficient management and regulation of anthropogenic point source inputs requires a demonstrated and measurable ecological effect. In all ecosystems, the evaluation of anthropogenic effects is confounded by the effects of naturally existing environmental factors and river nonpoin...

Metabolic syndrome and shift work: a systematic review.

PubMed

Canuto, Raquel; Garcez, Anderson S; Olinto, Maria T A

2013-12-01

The aim of this systematic review was to examine the association between shift work and metabolic syndrome (MetS) as well as the potential confounders investigated. A systematic search was conducted with the aim of finding original articles on the association between shift work and MetS. The included articles were chosen based on established inclusion criteria; their methodological quality was assessed using a validated quality checklist. A total of 10 articles were included in this review. The majority of the studies were classified as having a low risk of bias. The definitions of MetS and shift work varied between studies. Among the ten studies, eight found a positive association between shift work and MetS after controlling for socio-demographic and behavioral factors. Only three studies included sleep duration as a confounder, and these studies presented discordant results. We conclude that there was insufficient evidence regarding the association between shift work and prevalent MetS when the confounders are taken into account. Copyright © 2012 Elsevier Ltd. All rights reserved.

'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.

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.

Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

2011-01-01

Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

Occupational Stress and Physical Symptoms among Family Medicine Residents

PubMed Central

Choi, So-Myung; Park, Yong Soon; Kim, Go-Young

2013-01-01

Background The purpose of this study was to examine the levels of occupational stress and physical symptoms among family medicine residents and investigate the effect of subscales of occupational stress on physical symptoms. Methods A self-administered questionnaire survey of 1,152 family medicine residents was carried out via e-mail from April 2010 to July 2010. The response rate was 13.1% and the R (ver. 2.9.1) was used for the analysis of completed data obtained from 150 subjects. The questionnaire included demographic factors, resident training related factors, 24-items of the Korean Occupational Stress Scales and Korean Versions of the Wahler Physical Symptom Inventory. Results The total score of occupational stress of family medicine residents was relatively low compared to that of average workers. The scores of 'high job demand', 'inadequate social support', 'organizational injustice', and 'discomfort in occupational climate' were within the top 50%. Parameters associated with higher occupational stress included level of training, on-duty time, daily patient load, critical patient assigned, total working days, night duty day, sleep duration, and sleep quality. The six subscales of occupational stress, except for 'Job insecurity', had a significant positive correlation with physical symptom scores after adjustment had been made for potential confounders (total score, r = 0.325 and P < 0.001; high job demand, r = 0.439 and P < 0.001). Conclusion After the adjustment had been made for potential confounders, the total score of occupational stress and six subscales in family medicine residents showed a significant positive correlation with physical symptom scores. PMID:23372906

Bisphenol A and Peripheral Arterial Disease: Results from the NHANES

PubMed Central

Teppala, Srinivas; Sabanayagam, Charumathi

2012-01-01

Background: Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, and > 93% of U.S. adults have detectable levels of urinary BPA. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of cardiovascular disease (CVD), including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, few human studies have examined the association between markers of BPA exposure and CVD. Peripheral arterial disease (PAD) is a subclinical measure of atherosclerotic vascular disease and a strong independent risk factor for CVD and mortality. Objective: We examined the association between urinary BPA levels and PAD in a nationally representative sample of U.S. adults. Methods: We analyzed data from 745 participants in the National Health and Nutritional Examination Survey 2003–2004. We estimated associations between urinary BPA levels (in tertiles) and PAD (ankle–brachial index < 0.9, n = 63) using logistic regression models adjusted for potential confounders (age, sex, race/ethnicity, education, smoking, body mass index, diabetes mellitus, hypertension, urinary creatinine, estimated glomerular filtration rate, and serum cholesterol levels). Results: We observed a significant, positive association between increasing levels of urinary BPA and PAD before and after adjusting for confounders. The multivariable-adjusted odds ratio for PAD associated with the highest versus lowest tertile of urinary BPA was 2.69 (95% confidence interval: 1.02, 7.09; p-trend = 0.01). Conclusions: Urinary BPA levels were significantly associated with PAD, independent of traditional CVD risk factors. PMID:22645278

Design Issues in Small-Area Studies of Environment and Health

PubMed Central

Elliott, Paul; Savitz, David A.

2008-01-01

Background Small-area studies are part of the tradition of spatial epidemiology, which is concerned with the analysis of geographic patterns of disease with respect to environmental, demographic, socioeconomic, and other factors. We focus on etiologic research, where the aim is to make inferences about spatially varying environmental factors influencing the risk of disease. Methods and results We illustrate the approach through three exemplars: a) magnetic fields from overhead electric power lines and the occurrence of childhood leukemia, which illustrates the use of geographic information systems to focus on areas with high exposure prevalence; b) drinking-water disinfection by-products and reproductive outcomes, taking advantage of large between- to within-area variability in exposures from the water supply; and c) chronic exposure to air pollutants and cardiorespiratory health, where issues of socioeconomic confounding are particularly important. Discussion The small-area epidemiologic approach assigns exposure estimates to individuals based on location of residence or other geographic variables such as workplace or school. In this way, large populations can be studied, increasing the ability to investigate rare exposures or rare diseases. The approach is most effective when there is well-defined exposure variation across geographic units, limited within-area variation, and good control for potential confounding across areas. Conclusions In conjunction with traditional individual-based approaches, small-area studies offer a valuable addition to the armamentarium of the environmental epidemiologist. Modeling of exposure patterns coupled with collection of individual-level data on subsamples of the population should lead to improved risk estimates (i.e., less potential for bias) and help strengthen etiologic inference. PMID:18709174

Plasma lipid peroxidation and erythrocyte antioxidant enzymes status in workers exposed to cadmium.

PubMed

Babu, Kalahasthi Ravi; Rajmohan, Hirehal Raghavendra Rao; Rajan, Bagalur Krishna Murthy; Kumar, Karuna M

2006-09-01

Cadmium (Cd) is a corrosion-resistant metal, used extensively for electroplating in the automobile, electronic and aerospace industry. Only a few studies are available regarding Cd-induced oxidative stress in animals, but no reports are available regarding the effects of Cd on oxidative stress during occupational exposure. The present study was carried out to determine the plasma lipid peroxidation and erythrocyte antioxidant enzymes status in workers exposed to Cd during electroplating. 50 subjects exposed to Cd during electroplating formed the study group. An equal number of age-sex matched subjects, working in the administrative section, formed the control group. Urinary Cd levels were determined using the flameless atomic absorption spectrophotometer. Plasma lipid peroxidation and erythrocyte antioxidant enzymes were determined using spectrophotometric methods. A significant increase of plasma lipid peroxidation and a significant decrease of superoxide dismutase and glutathione peroxidase levels were noted in the study group compared with the control group. The level of plasma lipid peroxidation was positively and erythrocyte antioxidant enzymes were negatively and significantly associated with Cd levels in urine. Multiple regression analysis assessed the oxidative stress associated with Cd and other lifestyle confounding factors, such as age, body mass index, the consumption of vegetables, coffee, tea, smoking and alcohol. Analysis showed that the lifestyle confounding factors viz; smoking, body mass index and urinary Cd levels > 5 microg/g of creatinine, were significantly associated with oxidative stress. The results of the present study suggest that increased plasma lipid peroxidation and decreased superoxide dismutase levels could be used as biomarkers of oxidative stress in cadmium-exposed workers.

Is objectively measured sitting at work associated with low-back pain? A cross sectional study in the DPhacto cohort.

PubMed

Korshøj, Mette; Hallman, David M; Mathiassen, Svend Erik; Aadahl, Mette; Holtermann, Andreas; Jørgensen, Marie Birk

2018-01-01

Objectives Low-back pain (LBP) is a substantial health challenge due to the risk for long-term sickness absence and early retirement. Several biomechanical exposures at work, including sitting, have been suggested to increase the risk for LBP. The objectives of this study were to determine (i) the extent to which temporal patterns and total amount of objectively measured sitting is associated with LBP intensity and (ii) whether selected modifiers influence these associations. Methods This cross sectional study uses baseline data from the Danish PHysical ACTivity cohort with Objective measurements (DPhacto) of physical activities in the cleaning, transport and manufacturing sectors. Peak intensity of LBP was collected by questionnaire on a 0-10 scale and sitting was expressed in terms of total duration and temporal pattern, ie, time spent in brief bursts (≤5 minutes), moderate periods (>5-≤20 minutes), and prolonged periods of sitting (>20 minutes); both during work and whole day (waking hours only). Associations were determined using linear regression in models accounting for moderation and confounding. Factors evaluated as moderators or confounders were assessed by questionnaire. Results The population consisted of 704 participants. No significant associations were found between total duration or temporal patterns of sitting and LBP intensity, neither during work nor for the whole day. Body mass index (BMI) significantly moderated the association between sitting and LBP; participants with a high and low BMI showing a negative and positive association, respectively. Conclusion Sitting was not independently associated with peak LBP intensity, suggesting other exposures are more powerful risk factors for LBP.

The effect of heartburn and acid reflux on the severity of nausea and vomiting of pregnancy

PubMed Central

Gill, Simerpal Kaur; Maltepe, Caroline; Koren, Gideon

2009-01-01

BACKGROUND: Heartburn (HB) and acid reflux (RF) in the non-pregnant population can cause nausea and vomiting; therefore, it is plausible that in women with nausea and vomiting of pregnancy (NVP), HB/RF may increase the severity of symptoms. OBJECTIVE: To determine whether HB/RF during pregnancy contribute to increased severity of NVP. METHODS: A prospectively collected cohort of women who were experiencing NVP and HB, RF or both (n=194) was studied. The Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scale and its Well-being scale was used to compare the severity of the study cohort’s symptoms. This cohort was compared with a group of women experiencing NVP but no HB/RF (n=188). Multiple linear regression was used to control for the effects of confounding factors. RESULTS: Women with HB/RF reported higher PUQE scores (9.6±2.6) compared with controls (8.9±2.6) (P=0.02). Similarly, Well-being scores for women experiencing HB/RF were lower (4.3±2.1) compared with controls (4.9±2.0) (P=0.01). Multiple linear regression analysis demonstrated that increased PUQE scores (P=0.003) and decreased Well-being scores (P=0.005) were due to the presence of HB/RF as opposed to confounding factors such as pre-existing gastrointestinal conditions/symptoms, hyperemesis gravidarum in previous pregnancies and comorbidities. CONCLUSION: The present cohort study is the first to demonstrate that HB/RF are associated with increased severity of NVP. Managing HB/RF may improve the severity of NVP. PMID:19373420

Pulmonary function and fuel use: A population survey

PubMed Central

Saha, Asim; Mohan Rao, N; Kulkarni, PK; Majumdar, PK; Saiyed, HN

2005-01-01

Background In the backdrop of conflicting reports (some studies reported adverse outcomes of biomass fuel use whereas few studies reported absence of any association between adverse health effect and fuel use, may be due to presence of large number of confounding variables) on the respiratory health effects of biomass fuel use, this cross sectional survey was undertaken to understand the role of fuel use on pulmonary function. Method This study was conducted in a village of western India involving 369 randomly selected adult subjects (165 male and 204 female). All the subjects were interviewed and were subjected to pulmonary function test. Analysis of covariance was performed to compare the levels of different pulmonary function test parameters in relation to different fuel use taking care of the role of possible confounding factors. Results This study showed that biomass fuel use (especially wood) is an important factor for deterioration of pulmonary function (particularly in female). FEV1 (p < .05), FEV1 % (p < .01), PEFR (p < .05) and FEF25–75 (p < .01) values were significantly lower in biomass fuel using females than nonusers. Comparison of only biomass fuel use vs. only LPG (Liquefied Petroleum Gas) use and only wood vs. only LPG use has showed that LPG is a safer fuel so far as deterioration of pulmonary function is concerned. This study observes some deterioration of pulmonary function in the male subjects also, who came from biomass fuel using families. Conclusion This study concluded that traditional biomass fuels like wood have adverse effects on pulmonary function. PMID:16255784

Voice Outcomes of Adults Diagnosed with Pediatric Vocal Fold Nodules and Impact of Speech Therapy.

PubMed

Song, Brian H; Merchant, Maqdooda; Schloegel, Luke

2017-11-01

Objective To evaluate the voice outcomes of adults diagnosed with vocal fold nodules (VFNs) as children and to assess the impact of speech therapy on long-term voice outcomes. Study Design Prospective cohort study. Setting Large health care system. Subjects and Methods Subjects diagnosed with VFNs as children between the years 1996 and 2008 were identified within a medical record database of a large health care system. Included subjects were 3 to 12 years old at the time of diagnosis, had a documented laryngeal examination within 90 days of diagnosis, and were ≥18 years as of December 31, 2014. Qualified subjects were contacted by telephone and administered the Vocal Handicap Index-10 (VHI-10) and a 15-item questionnaire inquiring for confounding factors. Results A total of 155 subjects were included, with a mean age of 21.4 years (range, 18-29). The male:female ratio was 2.3:1. Mean VHI-10 score for the entire cohort was 5.4. Mean VHI-10 scores did not differ between those who received speech therapy (6.1) and those who did not (4.5; P = .08). Both groups were similar with respect to confounding risk factors that can contribute to dysphonia, although the no-therapy group had a disproportionately higher number of subjects who consumed >10 alcoholic drinks per week ( P = .01). Conclusion The majority of adults with VFNs as children will achieve a close-to-normal voice quality when they reach adulthood. In our cohort, speech therapy did not appear to have an impact on the long-term voice outcomes.

Flooding and mental health: a systematic mapping review.

PubMed

Fernandez, Ana; Black, John; Jones, Mairwen; Wilson, Leigh; Salvador-Carulla, Luis; Astell-Burt, Thomas; Black, Deborah

2015-01-01

Floods are the most common type of global natural disaster. Floods have a negative impact on mental health. Comprehensive evaluation and review of the literature are lacking. To systematically map and review available scientific evidence on mental health impacts of floods caused by extended periods of heavy rain in river catchments. We performed a systematic mapping review of published scientific literature in five languages for mixed studies on floods and mental health. PUBMED and Web of Science were searched to identify all relevant articles from 1994 to May 2014 (no restrictions). The electronic search strategy identified 1331 potentially relevant papers. Finally, 83 papers met the inclusion criteria. Four broad areas are identified: i) the main mental health disorders-post-traumatic stress disorder, depression and anxiety; ii] the factors associated with mental health among those affected by floods; iii) the narratives associated with flooding, which focuses on the long-term impacts of flooding on mental health as a consequence of the secondary stressors; and iv) the management actions identified. The quantitative and qualitative studies have consistent findings. However, very few studies have used mixed methods to quantify the size of the mental health burden as well as exploration of in-depth narratives. Methodological limitations include control of potential confounders and short-term follow up. Floods following extreme events were excluded from our review. Although the level of exposure to floods has been systematically associated with mental health problems, the paucity of longitudinal studies and lack of confounding controls precludes strong conclusions. We recommend that future research in this area include mixed-method studies that are purposefully designed, using more rigorous methods. Studies should also focus on vulnerable groups and include analyses of policy and practical responses.

Study design and statistical analysis of data in human population studies with the micronucleus assay.

PubMed

Ceppi, Marcello; Gallo, Fabio; Bonassi, Stefano

2011-01-01

The most common study design performed in population studies based on the micronucleus (MN) assay, is the cross-sectional study, which is largely performed to evaluate the DNA damaging effects of exposure to genotoxic agents in the workplace, in the environment, as well as from diet or lifestyle factors. Sample size is still a critical issue in the design of MN studies since most recent studies considering gene-environment interaction, often require a sample size of several hundred subjects, which is in many cases difficult to achieve. The control of confounding is another major threat to the validity of causal inference. The most popular confounders considered in population studies using MN are age, gender and smoking habit. Extensive attention is given to the assessment of effect modification, given the increasing inclusion of biomarkers of genetic susceptibility in the study design. Selected issues concerning the statistical treatment of data have been addressed in this mini-review, starting from data description, which is a critical step of statistical analysis, since it allows to detect possible errors in the dataset to be analysed and to check the validity of assumptions required for more complex analyses. Basic issues dealing with statistical analysis of biomarkers are extensively evaluated, including methods to explore the dose-response relationship among two continuous variables and inferential analysis. A critical approach to the use of parametric and non-parametric methods is presented, before addressing the issue of most suitable multivariate models to fit MN data. In the last decade, the quality of statistical analysis of MN data has certainly evolved, although even nowadays only a small number of studies apply the Poisson model, which is the most suitable method for the analysis of MN data.

Food preparation methods, drinking water source, and esophageal squamous cell carcinoma in the high-risk area of Golestan, Northeast Iran.

PubMed

Golozar, Asieh; Etemadi, Arash; Kamangar, Farin; Fazeltabar Malekshah, Akbar; Islami, Farhad; Nasrollahzadeh, Dariush; Abedi-Ardekani, Behnoosh; Khoshnia, Masoud; Pourshams, Akram; Semnani, Shahriar; Marjani, Haji Amin; Shakeri, Ramin; Sotoudeh, Masoud; Brennan, Paul; Taylor, Philip; Boffetta, Paolo; Abnet, Christian; Dawsey, Sanford; Malekzadeh, Reza

2016-03-01

Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders.

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

PubMed

Spertus, Jacob V; Normand, Sharon-Lise T

2018-04-23

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

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.

Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala.

PubMed

Boy, Erick; Bruce, Nigel; Delgado, Hernán

2002-01-01

In this study, we aimed to establish whether domestic use of wood fuel is associated with reduced birth weight, independent of key maternal, social, and economic confounding factors. We studied 1,717 women and newborn children in rural and urban communities in rural Guatemala. We identified subjects through home births reported by traditional birth attendants in six rural districts (n = 572) and all public hospital births in Quetzaltenango city during the study period (n = 1,145). All were seen within 72 hr of delivery, and data were collected on the type of household fuel used, fire type, and socioeconomic and other confounding factors. Smoking among women in the study community was negligible. Children born to mothers habitually cooking on open fires (n = 861) had the lowest mean birth weight of 2,819 g [95% confidence interval (CI), 2,790-2,848]; those using a chimney stove (n = 490) had an intermediate mean of 2,863 g (95% CI, 2,824-2,902); and those using the cleanest fuels (electricity or gas, n = 365) had the highest mean of 2,948 g (95% CI, 2,898-2,998) (p< 0.0001). The percentage of low birth weights (< 500 g) in these three groups was 19.9% (open fire), 16.8% (chimney stove), and 16.0% (electricity/gas), (trend (p = 0.08). Confounding factors were strongly associated with fuel type, but after adjustment wood users still had a birth weight 63 g lower (p = 0.05; 95% CI, 0.4-126). This is the first report of an association between biofuel use and reduced birth weight in a human population. Although there is potential for residual confounding despite adjustment, the better-documented evidence on passive smoking and a feasible mechanism through carbon monoxide exposure suggest this association may be real. Because two-thirds of households in developing countries still rely on biofuels and women of childbearing age perform most cooking tasks, the attributable risk arising from this association, if confirmed, could be substantial.

Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala.

PubMed Central

Boy, Erick; Bruce, Nigel; Delgado, Hernán

2002-01-01

In this study, we aimed to establish whether domestic use of wood fuel is associated with reduced birth weight, independent of key maternal, social, and economic confounding factors. We studied 1,717 women and newborn children in rural and urban communities in rural Guatemala. We identified subjects through home births reported by traditional birth attendants in six rural districts (n = 572) and all public hospital births in Quetzaltenango city during the study period (n = 1,145). All were seen within 72 hr of delivery, and data were collected on the type of household fuel used, fire type, and socioeconomic and other confounding factors. Smoking among women in the study community was negligible. Children born to mothers habitually cooking on open fires (n = 861) had the lowest mean birth weight of 2,819 g [95% confidence interval (CI), 2,790-2,848]; those using a chimney stove (n = 490) had an intermediate mean of 2,863 g (95% CI, 2,824-2,902); and those using the cleanest fuels (electricity or gas, n = 365) had the highest mean of 2,948 g (95% CI, 2,898-2,998) (p< 0.0001). The percentage of low birth weights (< 500 g) in these three groups was 19.9% (open fire), 16.8% (chimney stove), and 16.0% (electricity/gas), (trend (p = 0.08). Confounding factors were strongly associated with fuel type, but after adjustment wood users still had a birth weight 63 g lower (p = 0.05; 95% CI, 0.4-126). This is the first report of an association between biofuel use and reduced birth weight in a human population. Although there is potential for residual confounding despite adjustment, the better-documented evidence on passive smoking and a feasible mechanism through carbon monoxide exposure suggest this association may be real. Because two-thirds of households in developing countries still rely on biofuels and women of childbearing age perform most cooking tasks, the attributable risk arising from this association, if confirmed, could be substantial. PMID:11781172

Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

PubMed

Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

2016-03-01

Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

Modifiable risk factors for chronic back pain: insights using the co-twin control design.

PubMed

Suri, Pradeep; Boyko, Edward J; Smith, Nicholas L; Jarvik, Jeffrey G; Williams, Frances M K; Jarvik, Gail P; Goldberg, Jack

2017-01-01

Inconsistent associations between modifiable risk factors and chronic back pain (CBP) may be due to the inability of traditional epidemiologic study designs to properly account for an array of potential genetic and environmental confounding factors. The co-twin control research design, comparing modifiable risk factors in twins discordant for CBP, offers a unique way to remove numerous confounding factors. The study aimed to examine the association of modifiable lifestyle and psychological factors with lifetime CBP. This is a cross-sectional co-twin control study in a nationwide sample of male twin members of the Vietnam Era Twin Registry. The sample is composed of 7,108 participants, including 1,308 monozygotic (MZ) pairs and 793 dizygotic pairs. The outcome measure is the self-reported lifetime history of CBP. Lifestyle factors included body mass index (BMI), smoking history, alcohol consumption, habitual physical activity, and typical sleep duration. Psychological factors included depression (Patient Health Questionnaire-9) and posttraumatic stress disorder (PTSD) symptoms (PTSD Checklist). Covariates included age, race, education, and income. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the association of risk factors with lifetime CBP when considering twins as individuals, and a within-pair co-twin control analysis that accounted for familial and genetic factors. Funding was through VA Grant 5IK2RX001515; there were no study-specific conflicts of interest. The mean age of respondents was 62 years and the prevalence of lifetime CBP was 28%. All lifestyle factors were associated with CBP in the individual level analysis. However, none of these persisted in the within-pair analyses, except for severe obesity (BMI ≥35.0), which was associated with lifetime CBP in both individual-level (OR=1.6, 95% CI: 1.3-1.9) and within-pair analyses (MZ analysis: OR=3.7, 95% CI: 1.2-11.4). Symptoms of PTSD and depression were strongly associated with lifetime CBP in both the individual-level (moderate or severe depression: OR=4.2, 95% CI: 3.6-4.9, and severe PTSD: OR=4.8, 95% CI: 4.0-5.7) and within-pair (MZ) analyses (moderate or severe depression: OR=4.6, 95% CI: 2.4-8.7, and severe PTSD: OR=3.2, 95% CI: 1.6-6.5). Many associations between modifiable lifestyle risk factors and CBP are due to confounding by familial and genetic factors. Severe obesity, depression, and PTSD should be considered in the development of intervention strategies to reduce the prevalence of CBP. Published by Elsevier Inc.

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

PubMed

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

2016-09-01

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

Comparative analyses of studies of childhood leukemia and magnetic fields, radon and gamma radiation.

PubMed

Kheifets, Leeka; Swanson, John; Yuan, Yingzhe; Kusters, Cynthia; Vergara, Ximena

2017-06-26

In this paper we compare the findings of epidemiologic studies of childhood leukemia that examined at least two of ELF magnetic fields and/or distance to power lines, and exposure to radon and gamma radiation or distance to nuclear plants. Many of the methodologic aspects are common to studies of non-ionising (i.e. ELF-MF) and ionising radiation. A systematic search and review of studies with more than one exposure under study identified 33 key and 35 supplementary papers from ten countries that have been included in this review. Examining studies that have looked at several radiation exposures, and comparing similarities and differences for the different types of radiation, through the use of directed acyclic graphs, we evaluate to what extent bias, confounding and other methodological issues might be operating in these studies. We found some indication of bias, although results are not clear cut. There is little evidence that confounding has had a substantial influence on results. Influence of the residential mobility on the study conduct and interpretation is complex and can manifest as a selection bias, confounding, increased measurement error or could also be a potential risk factor. Other factors associated with distance to power lines and to nuclear power plants should be investigated. A more complete and consistent reporting of results in the future studies will allow for a more informative comparison across studies and integration of results.

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

PubMed Central

Gardener, Hannah; Buka, Stephen L.

2008-01-01

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

Insulin-Like Growth Factor-1 Bioactivity Plays a Prosurvival Role in Older Participants

PubMed Central

2013-01-01

The aim of this study was to address the intriguing issue of the role of the insulin-like growth factor (IGF)-1 system in longevity looking at the role of different components of IGF system. Vital status was ascertained in 1,197 men and women aged greater than or equal to 65 years from the InCHIANTI study. Hormonal levels were categorized into quartiles, and ratio of IGF-1 to IGF-binding protein (IGFBP)-1 was calculated. The relationship between hormones and mortality was tested by Cox proportional hazard models adjusted for age, sex, and confounders. During the 8-year follow-up period, 240 died and 957 survived. Lowest quartiles of IGF-1 and IGFBP-1 were considered as reference. Compared with the lowest quartiles, IGF-1 in upper quartiles was a negative predictor of mortality independent of age and sex (p = .01) but not independent of IGFBP-1 and other confounders. IGFBP-1 in second–third quartiles was negatively associated and that in the fourth quartiles was positively associated with risk of death. IGF-1/IGFBP-1 ratio in the lowest quartiles was a strong positive predictor of mortality, in age- and sex-adjusted model (p = .005), and independent of additional confounders (p = .037). High IGFBP-1 and low IGF-1/IGFBP-1 ratio are associated with all-cause mortality in older population. PMID:23671288

Insulin-like growth factor-1 bioactivity plays a prosurvival role in older participants.

PubMed

Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Bandinelli, Stefania; De Vita, Francesca; Dall'Aglio, Elisabetta; Corsonello, Andrea; Lattanzio, Fabrizia; Paolisso, Giuseppe; Ferrucci, Luigi; Ceda, Gian Paolo

2013-11-01

The aim of this study was to address the intriguing issue of the role of the insulin-like growth factor (IGF)-1 system in longevity looking at the role of different components of IGF system. Vital status was ascertained in 1,197 men and women aged greater than or equal to 65 years from the InCHIANTI study. Hormonal levels were categorized into quartiles, and ratio of IGF-1 to IGF-binding protein (IGFBP)-1 was calculated. The relationship between hormones and mortality was tested by Cox proportional hazard models adjusted for age, sex, and confounders. During the 8-year follow-up period, 240 died and 957 survived. Lowest quartiles of IGF-1 and IGFBP-1 were considered as reference. Compared with the lowest quartiles, IGF-1 in upper quartiles was a negative predictor of mortality independent of age and sex (p = .01) but not independent of IGFBP-1 and other confounders. IGFBP-1 in second-third quartiles was negatively associated and that in the fourth quartiles was positively associated with risk of death. IGF-1/IGFBP-1 ratio in the lowest quartiles was a strong positive predictor of mortality, in age- and sex-adjusted model (p = .005), and independent of additional confounders (p = .037). High IGFBP-1 and low IGF-1/IGFBP-1 ratio are associated with all-cause mortality in older population.

Population-Level Seasonality in Cardiovascular Mortality, Blood Pressure, BMI and Inflammatory Cells in UK Biobank.

PubMed

Wyse, Cathy A; Celis Morales, Carlos A; Ward, Joey; Lyall, Donald; Smith, Daniel J; Mackay, Daniel; Curtis, Annie M; Bailey, Mark E S; Biello, Stephany; Gill, Jason M R; Pell, J P

2018-05-03

Introduction The risk of mortality from cardiovascular disease (CVD) is higher in wintertime throughout the world, but it is not known if this reflects annual changes in diet or lifestyle, or an endogenous photoperiodic mechanism that is sensitive to changes in daylength. Methods Phenotypic data on cardiometabolic and lifestyle factors were collected throughout a 4 year time period from 502,642 middle-aged participants in UK Biobank. To assess the impact of seasonal environmental changes on cardiovascular risk factors, we linked these data to the outdoor temperature and day length at the time of assessment. Self-reported information on physical activity, diet and disease status were used to adjust for confounding factors related to health and lifestyle. Results Mortality related to CVD was higher in winter, as were risk factors for this condition including blood pressure, markers of inflammation and BMI. These seasonal rhythms were significantly related to day length after adjustment for other factors that might affect seasonality including physical activity, diet and outdoor temperature. Conclusions The risk of CVD may be modulated by day length at temperate latitudes, and the implications of seasonality should be considered in all studies of human cardiometabolic health.

Correction of odds ratios in case-control studies for exposure misclassification with partial knowledge of the degree of agreement among experts who assessed exposures.

PubMed

Burstyn, Igor; Gustafson, Paul; Pintos, Javier; Lavoué, Jérôme; Siemiatycki, Jack

2018-02-01

Estimates of association between exposures and diseases are often distorted by error in exposure classification. When the validity of exposure assessment is known, this can be used to adjust these estimates. When exposure is assessed by experts, even if validity is not known, we sometimes have information about interrater reliability. We present a Bayesian method for translating the knowledge of interrater reliability, which is often available, into knowledge about validity, which is often needed but not directly available, and applying this to correct odds ratios (OR). The method allows for inclusion of observed potential confounders in the analysis, as is common in regression-based control for confounding. Our method uses a novel type of prior on sensitivity and specificity. The approach is illustrated with data from a case-control study of lung cancer risk and occupational exposure to diesel engine emissions, in which exposure assessment was made by detailed job history interviews with study subjects followed by expert judgement. Using interrater agreement measured by kappas (κ), we estimate sensitivity and specificity of exposure assessment and derive misclassification-corrected confounder-adjusted OR. Misclassification-corrected and confounder-adjusted OR obtained with the most defensible prior had a posterior distribution centre of 1.6 with 95% credible interval (Crl) 1.1 to 2.6. This was on average greater in magnitude than frequentist point estimate of 1.3 (95% Crl 1.0 to 1.7). The method yields insights into the degree of exposure misclassification and appears to reduce attenuation bias due to misclassification of exposure while the estimated uncertainty increased. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Low socioeconomic status is a risk factor for preeclampsia: the Generation R Study.

PubMed

Silva, Lindsay M; Coolman, Marianne; Steegers, Eric Ap; Jaddoe, Vincent Wv; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

2008-06-01

To examine whether maternal socioeconomic status, as indicated by maternal educational level, is associated with preeclampsia, and if so, to what extent known risk factors for preeclampsia mediate the effect of educational level. In the Generation R Study, a population-based cohort study, we examined data of 3547 pregnant women. Odds ratios of preeclampsia for low, mid-low and mid-high educational level compared with high educational level were calculated after adjustment for confounders and additional adjustment for a selection of potential mediators (family history, material factors, psychosocial factors, substance use, working conditions, preexisting medical conditions, maternal anthropometrics and blood pressure at enrollment) that individually caused more than 10% change in the odds ratio for low education. Adjusted for the confounding effects of age, gravidity and multiple pregnancy, women with low educational level were more likely to develop preeclampsia (odds ratio 5.12; 95% confidence interval: 2.20, 11.93) than women with high educational level. After additional adjustment for financial difficulties, smoking in pregnancy, working conditions, body mass index and blood pressure at enrollment, the odds ratio was 4.91 (95% confidence interval: 1.93, 12.52). Low maternal socioeconomic status is a strong risk factor for preeclampsia. Only a small part of this association can be explained by the mediating effects of established risk factors for preeclampsia. Further research is needed to disentangle the pathway from low socioeconomic status to preeclampsia.

The impacts of speed cameras on road accidents: an application of propensity score matching methods.

PubMed

Li, Haojie; Graham, Daniel J; Majumdar, Arnab

2013-11-01

This paper aims to evaluate the impacts of speed limit enforcement cameras on reducing road accidents in the UK by accounting for both confounding factors and the selection of proper reference groups. The propensity score matching (PSM) method is employed to do this. A naïve before and after approach and the empirical Bayes (EB) method are compared with the PSM method. A total of 771 sites and 4787 sites for the treatment and the potential reference groups respectively are observed for a period of 9 years in England. Both the PSM and the EB methods show similar results that there are significant reductions in the number of accidents of all severities at speed camera sites. It is suggested that the propensity score can be used as the criteria for selecting the reference group in before-after control studies. Speed cameras were found to be most effective in reducing accidents up to 200 meters from camera sites and no evidence of accident migration was found. Copyright © 2013 Elsevier Ltd. All rights reserved.

Correction of motion artifacts and serial correlations for real-time functional near-infrared spectroscopy

PubMed Central

Barker, Jeffrey W.; Rosso, Andrea L.; Sparto, Patrick J.; Huppert, Theodore J.

2016-01-01

Abstract. Functional near-infrared spectroscopy (fNIRS) is a relatively low-cost, portable, noninvasive neuroimaging technique for measuring task-evoked hemodynamic changes in the brain. Because fNIRS can be applied to a wide range of populations, such as children or infants, and under a variety of study conditions, including those involving physical movement, gait, or balance, fNIRS data are often confounded by motion artifacts. Furthermore, the high sampling rate of fNIRS leads to high temporal autocorrelation due to systemic physiology. These two factors can reduce the sensitivity and specificity of detecting hemodynamic changes. In a previous work, we showed that these factors could be mitigated by autoregressive-based prewhitening followed by the application of an iterative reweighted least squares algorithm offline. This current work extends these same ideas to real-time analysis of brain signals by modifying the linear Kalman filter, resulting in an algorithm for online estimation that is robust to systemic physiology and motion artifacts. We evaluated the performance of the proposed method via simulations of evoked hemodynamics that were added to experimental resting-state data, which provided realistic fNIRS noise. Last, we applied the method post hoc to data from a standing balance task. Overall, the new method showed good agreement with the analogous offline algorithm, in which both methods outperformed ordinary least squares methods. PMID:27226974

Impact of occupational stress and other psychosocial factors on musculoskeletal pain among Chinese offshore oil installation workers

PubMed Central

Chen, W; Yu, I; Wong, T

2005-01-01

Aims: To explore the relation between psychosocial factors and musculoskeletal pain in Chinese offshore oil installation workers. Methods: Half of all offshore workers (being a representative sample) in a Chinese oil company were invited to complete a self-administered questionnaire providing information on sociodemographic characteristics, occupational stressors, type A behaviour, social support, coping style, health related behaviour, past injuries, and musculoskeletal pain. Factor analysis was used to identify the sources of occupational stress and the domains of type A behaviour and coping style. Logistic regression analyses were used to study the relations between psychosocial factors and musculoskeletal pain in each body region. Results: The prevalence of musculoskeletal pain over the previous 12 months varied between 7.5% for elbow pain and 32% for low back pain; 56% workers had at least one complaint. Significant associations were found between various psychosocial factors and musculoskeletal pain in different body regions after adjusting for potential confounding factors. Occupational stressors, in particular stress from safety, physical environment, and ergonomics, were important predictors of musculoskeletal pain, as was coping by eating behaviour. Conclusions: These observations supported the widely accepted biopsychosocial model of musculoskeletal disorders and suggested that in future studies of work related musculoskeletal disorders, psychosocial factors must be given due consideration. PMID:15778258

Prevention of motor‐vehicle deaths by changing vehicle factors

PubMed Central

Robertson, Leon S

2007-01-01

Objective To estimate the effect of changing vehicle factors to reduce mortality in a comprehensive study. Design/methods Odds of death in the United States during 2000–2005 were analyzed, involving specific makes and models of 1999–2005 model year cars, minivans, and sport utility vehicles using logistic regression after selection of factors to be included by examination of least‐squares correlations of vehicle factors to maximize independence of predictors. Based on the regression coefficients, percentages of deaths preventable by changes in selected factors were calculated. Correlations of vehicle characteristics to environmental and behavioral risk factors were also examined to assess any potential confounding. Results Deaths in the studied vehicles would have been 42% lower had all had electronic stability control (ESC) systems. Improved crashworthiness as measured by offset frontal and side crash tests would have produced an additional 28% reduction, and static stability improvement would have reduced the deaths 11%. Although weight–power that reduces fuel economy is associated with lower risk to drivers, it increases risk of deaths to pedestrians and bicyclists but has an overall minor effect compared to the other factors. Conclusion A large majority of motor‐vehicle‐related fatalities could be avoided by universal adoption of the most effective technologies. PMID:17916886

Hypertension and arterial stiffness in heart transplantation patients

PubMed Central

de Souza-Neto, João David; de Oliveira, Ítalo Martins; Lima-Rocha, Hermano Alexandre; Oliveira-Lima, José Wellington; Bacal, Fernando

2016-01-01

OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension. PMID:27652829

Introduction to the use of regression models in epidemiology.

PubMed

Bender, Ralf

2009-01-01

Regression modeling is one of the most important statistical techniques used in analytical epidemiology. By means of regression models the effect of one or several explanatory variables (e.g., exposures, subject characteristics, risk factors) on a response variable such as mortality or cancer can be investigated. From multiple regression models, adjusted effect estimates can be obtained that take the effect of potential confounders into account. Regression methods can be applied in all epidemiologic study designs so that they represent a universal tool for data analysis in epidemiology. Different kinds of regression models have been developed in dependence on the measurement scale of the response variable and the study design. The most important methods are linear regression for continuous outcomes, logistic regression for binary outcomes, Cox regression for time-to-event data, and Poisson regression for frequencies and rates. This chapter provides a nontechnical introduction to these regression models with illustrating examples from cancer research.

Family structure and risk behaviors: the role of the family meal in assessing likelihood of adolescent risk behaviors

PubMed Central

Goldfarb, Samantha; Tarver, Will L; Sen, Bisakha

2014-01-01

Background Previous literature has asserted that family meals are a key protective factor for certain adolescent risk behaviors. It is suggested that the frequency of eating with the family is associated with better psychological well-being and a lower risk of substance use and delinquency. However, it is unclear whether there is evidence of causal links between family meals and adolescent health-risk behaviors. Purpose The purpose of this article is to review the empirical literature on family meals and adolescent health behaviors and outcomes in the US. Data sources A search was conducted in four academic databases: Social Sciences Full Text, Sociological Abstracts, PsycINFO®, and PubMed/MEDLINE. Study selection We included studies that quantitatively estimated the relationship between family meals and health-risk behaviors. Data extraction Data were extracted on study sample, study design, family meal measurement, outcomes, empirical methods, findings, and major issues. Data synthesis Fourteen studies met the inclusion criteria for the review that measured the relationship between frequent family meals and various risk-behavior outcomes. The outcomes considered by most studies were alcohol use (n=10), tobacco use (n=9), and marijuana use (n=6). Other outcomes included sexual activity (n=2); depression, suicidal ideation, and suicide attempts (n=4); violence and delinquency (n=4); school-related issues (n=2); and well-being (n=5). The associations between family meals and the outcomes of interest were most likely to be statistically significant in unadjusted models or models controlling for basic family characteristics. Associations were less likely to be statistically significant when other measures of family connectedness were included. Relatively few analyses used sophisticated empirical techniques available to control for confounders in secondary data. Conclusion More research is required to establish whether or not the relationship between family dinners and risky adolescent behaviors is an artifact of underlying confounders. We recommend that researchers make more frequent use of sophisticated methods to reduce the problem of confounders in secondary data, and that the scope of adolescent problem behaviors also be further widened. PMID:24627645

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

Advancing Research on Racial–Ethnic Health Disparities: Improving Measurement Equivalence in Studies with Diverse Samples

PubMed Central

Landrine, Hope; Corral, Irma

2014-01-01

To conduct meaningful, epidemiologic research on racial–ethnic health disparities, racial–ethnic samples must be rendered equivalent on other social status and contextual variables via statistical controls of those extraneous factors. The racial–ethnic groups must also be equally familiar with and have similar responses to the methods and measures used to collect health data, must have equal opportunity to participate in the research, and must be equally representative of their respective populations. In the absence of such measurement equivalence, studies of racial–ethnic health disparities are confounded by a plethora of unmeasured, uncontrolled correlates of race–ethnicity. Those correlates render the samples, methods, and measures incomparable across racial–ethnic groups, and diminish the ability to attribute health differences discovered to race–ethnicity vs. to its correlates. This paper reviews the non-equivalent yet normative samples, methodologies and measures used in epidemiologic studies of racial–ethnic health disparities, and provides concrete suggestions for improving sample, method, and scalar measurement equivalence. PMID:25566524

Improved application of independent component analysis to functional magnetic resonance imaging study via linear projection techniques.

PubMed

Long, Zhiying; Chen, Kewei; Wu, Xia; Reiman, Eric; Peng, Danling; Yao, Li

2009-02-01

Spatial Independent component analysis (sICA) has been widely used to analyze functional magnetic resonance imaging (fMRI) data. The well accepted implicit assumption is the spatially statistical independency of intrinsic sources identified by sICA, making the sICA applications difficult for data in which there exist interdependent sources and confounding factors. This interdependency can arise, for instance, from fMRI studies investigating two tasks in a single session. In this study, we introduced a linear projection approach and considered its utilization as a tool to separate task-related components from two-task fMRI data. The robustness and feasibility of the method are substantiated through simulation on computer data and fMRI real rest data. Both simulated and real two-task fMRI experiments demonstrated that sICA in combination with the projection method succeeded in separating spatially dependent components and had better detection power than pure model-based method when estimating activation induced by each task as well as both tasks.

From Correlates to Causes: Can Quasi-Experimental Studies and Statistical Innovations Bring Us Closer to Identifying the Causes of Antisocial Behavior?

PubMed Central

Jaffee, Sara R.; Strait, Luciana B.; Odgers, Candice L.

2011-01-01

Longitudinal, epidemiological studies have identified robust risk factors for youth antisocial behavior, including harsh and coercive discipline, maltreatment, smoking during pregnancy, divorce, teen parenthood, peer deviance, parental psychopathology, and social disadvantage. Nevertheless, because this literature is largely based on observational studies, it remains unclear whether these risk factors have truly causal effects. Identifying causal risk factors for antisocial behavior would be informative for intervention efforts and for studies that test whether individuals are differentially susceptible to risk exposures. In this paper, we identify the challenges to causal inference posed by observational studies and describe quasi-experimental methods and statistical innovations that may move us beyond discussions of risk factors to allow for stronger causal inference. We then review studies that use these methods and we evaluate whether robust risk factors identified from observational studies are likely to play a causal role in the emergence and development of youth antisocial behavior. For most of the risk factors we review, there is evidence that they have causal effects. However, these effects are typically smaller than those reported in observational studies, suggesting that familial confounding, social selection, and misidentification might also explain some of the association between risk exposures and antisocial behavior. For some risk factors (e.g., smoking during pregnancy, parent alcohol problems) the evidence is weak that they have environmentally mediated effects on youth antisocial behavior. We discuss the implications of these findings for intervention efforts to reduce antisocial behavior and for basic research on the etiology and course of antisocial behavior. PMID:22023141

From correlates to causes: can quasi-experimental studies and statistical innovations bring us closer to identifying the causes of antisocial behavior?

PubMed

Jaffee, Sara R; Strait, Luciana B; Odgers, Candice L

2012-03-01

Longitudinal, epidemiological studies have identified robust risk factors for youth antisocial behavior, including harsh and coercive discipline, maltreatment, smoking during pregnancy, divorce, teen parenthood, peer deviance, parental psychopathology, and social disadvantage. Nevertheless, because this literature is largely based on observational studies, it remains unclear whether these risk factors have truly causal effects. Identifying causal risk factors for antisocial behavior would be informative for intervention efforts and for studies that test whether individuals are differentially susceptible to risk exposures. In this article, we identify the challenges to causal inference posed by observational studies and describe quasi-experimental methods and statistical innovations that may move researchers beyond discussions of risk factors to allow for stronger causal inference. We then review studies that used these methods, and we evaluate whether robust risk factors identified from observational studies are likely to play a causal role in the emergence and development of youth antisocial behavior. There is evidence of causal effects for most of the risk factors we review. However, these effects are typically smaller than those reported in observational studies, suggesting that familial confounding, social selection, and misidentification might also explain some of the association between risk exposures and antisocial behavior. For some risk factors (e.g., smoking during pregnancy, parent alcohol problems), the evidence is weak that they have environmentally mediated effects on youth antisocial behavior. We discuss the implications of these findings for intervention efforts to reduce antisocial behavior and for basic research on the etiology and course of antisocial behavior.

Development of a minimization instrument for allocation of a hospital-level performance improvement intervention to reduce waiting times in Ontario emergency departments.

PubMed

Leaver, Chad Andrew; Guttmann, Astrid; Zwarenstein, Merrick; Rowe, Brian H; Anderson, Geoff; Stukel, Therese; Golden, Brian; Bell, Robert; Morra, Dante; Abrams, Howard; Schull, Michael J

2009-06-08

Rigorous evaluation of an intervention requires that its allocation be unbiased with respect to confounders; this is especially difficult in complex, system-wide healthcare interventions. We developed a short survey instrument to identify factors for a minimization algorithm for the allocation of a hospital-level intervention to reduce emergency department (ED) waiting times in Ontario, Canada. Potential confounders influencing the intervention's success were identified by literature review, and grouped by healthcare setting specific change stages. An international multi-disciplinary (clinical, administrative, decision maker, management) panel evaluated these factors in a two-stage modified-delphi and nominal group process based on four domains: change readiness, evidence base, face validity, and clarity of definition. An original set of 33 factors were identified from the literature. The panel reduced the list to 12 in the first round survey. In the second survey, experts scored each factor according to the four domains; summary scores and consensus discussion resulted in the final selection and measurement of four hospital-level factors to be used in the minimization algorithm: improved patient flow as a hospital's leadership priority; physicians' receptiveness to organizational change; efficiency of bed management; and physician incentives supporting the change goal. We developed a simple tool designed to gather data from senior hospital administrators on factors likely to affect the success of a hospital patient flow improvement intervention. A minimization algorithm will ensure balanced allocation of the intervention with respect to these factors in study hospitals.

MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample.

PubMed

Zhao, Jinying; Forsberg, Christopher W; Goldberg, Jack; Smith, Nicholas L; Vaccarino, Viola

2012-11-02

Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease.

The “Insight Paradox” in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression

PubMed Central

Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

2016-01-01

The so-called “insight paradox” posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. PMID:27069064

Serum 25-hydroxyvitamin D level is associated with myopia in the Korea national health and nutrition examination survey.

PubMed

Kwon, Jin-Woo; Choi, Jin A; La, Tae Yoon

2016-11-01

The aim of this article was to assess the associations of serum 25-hydroxyvitamin D [25(OH)D] and daily sun exposure time with myopia in Korean adults.This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) of Korean adults in 2010-2012; multiple logistic regression analyses were performed to examine the associations of serum 25(OH)D levels and daily sun exposure time with myopia, defined as spherical equivalent ≤-0.5D, after adjustment for age, sex, household income, body mass index (BMI), exercise, intraocular pressure (IOP), and education level. Also, multiple linear regression analyses were performed to examine the relationship between serum 25(OH)D levels with spherical equivalent after adjustment for daily sun exposure time in addition to the confounding factors above.Between the nonmyopic and myopic groups, spherical equivalent, age, IOP, BMI, waist circumference, education level, household income, and area of residence differed significantly (all P < 0.05). Compared with subjects with daily sun exposure time <2 hour, subjects with sun exposure time ≥2 to <5 hour, and those with sun exposure time ≥5 hour had significantly less myopia (P < 0.001). In addition, compared with subjects were categorized into quartiles of serum 25(OH)D, the higher quartiles had gradually lower prevalences of myopia after adjustment for confounding factors (P < 0.001). In multiple linear regression analyses, spherical equivalent was significantly associated with serum 25(OH)D concentration after adjustment for confounding factors (P = 0.002).Low serum 25(OH)D levels and shorter daily sun exposure time may be independently associated with a high prevalence of myopia in Korean adults. These data suggest a direct role for vitamin D in the development of myopia.

The "Insight Paradox" in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression.

PubMed

Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

2016-09-01

The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2018-02-01

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

Periodontal disease is associated with higher levels of C-reactive protein in non-diabetic, non-smoking acute myocardial infarction patients.

PubMed

Kodovazenitis, George; Pitsavos, Christos; Papadimitriou, Lambros; Deliargyris, Efthymios N; Vrotsos, Ioannis; Stefanadis, Christodoulos; Madianos, Phoebus N

2011-12-01

A link between periodontal disease (PD) and cardiovascular events has been proposed, but confounding by shared risk factors such as smoking and diabetes remains a concern. We examined the prevalence of PD and its contribution to C-reactive protein (CRP) levels in acute myocardial infarction (AMI) patients and in subjects without AMI and with angiographically nonobstructive coronary disease in the absence of these confounding risk factors. Periodontal status and admission CRP levels were evaluated in 87 non-diabetic and non-smoking subjects undergoing cardiac catheterization. The study group comprised of 47 patients with documented AMI, and 40 subjects without AMI and with angiographically nonobstructive coronary disease (ANCD group). Both the prevalence of PD and CRP levels were significantly higher in AMI patients compared with ANCD subjects (38.3% vs. 17.5%, p=0.03 and 44.3 vs. 8.5 mg/L, p<0.001 respectively). PD was associated with higher CRP levels in AMI patients (52.5 vs. 36.1 mg/L, p=0.04) as well as in ANCD subjects, however, in this group this was not significant (12.6 vs. 7.6 mg/L, p=0.5). Multivariable regression analysis confirmed two separate measures of PD as strong and independent contributors to elevated CRP levels in AMI patients (R2 = 0.28, R2 = 0.30, p=0.001). PD contributes to elevated CRP levels in non-diabetic, non-smoking AMI patients, independently of other confounding factors. These findings imply that periodontitis may emerge as a novel target for reducing future risk in AMI survivors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia.

PubMed

Naucler, Pontus; Darenberg, Jessica; Morfeldt, Eva; Ortqvist, Ake; Henriques Normark, Birgitta

2013-06-01

Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients <45 years of age to 26.1% in patients aged ≥85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with β-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies.

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

Photosynthetic responses to temperature across leaf-canopy-ecosystem scales: a 15-year study in a Californian oak-grass savanna.

PubMed

Ma, Siyan; Osuna, Jessica L; Verfaillie, Joseph; Baldocchi, Dennis D

2017-06-01

Ecosystem CO 2 fluxes measured with eddy-covariance techniques provide a new opportunity to retest functional responses of photosynthesis to abiotic factors at the ecosystem level, but examining the effects of one factor (e.g., temperature) on photosynthesis remains a challenge as other factors may confound under circumstances of natural experiments. In this study, we developed a data mining framework to analyze a set of ecosystem CO 2 fluxes measured from three eddy-covariance towers, plus a suite of abiotic variables (e.g., temperature, solar radiation, air, and soil moisture) measured simultaneously, in a Californian oak-grass savanna from 2000 to 2015. Natural covariations of temperature and other factors caused remarkable confounding effects in two particular conditions: lower light intensity at lower temperatures and drier air and soil at higher temperatures. But such confounding effects may cancel out. At the ecosystem level, photosynthetic responses to temperature did follow a quadratic function on average. The optimum value of photosynthesis occurred within a narrow temperature range (i.e., optimum temperature, T opt ): 20.6 ± 0.6, 18.5 ± 0.7, 19.2 ± 0.5, and 19.0 ± 0.6 °C for the oak canopy, understory grassland, entire savanna, and open grassland, respectively. This paradigm confirms that photosynthesis response to ambient temperature changes is a functional relationship consistent across leaf-canopy-ecosystem scales. Nevertheless, T opt can shift with variations in light intensity, air dryness, or soil moisture. These findings will pave the way to a direct determination of thermal optima and limits of ecosystem photosynthesis, which can in turn provide a rich resource for baseline thresholds and dynamic response functions required for predicting global carbon balance and geographic shifts of vegetative communities in response to climate change.

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.

Relationship between stress-related psychosocial work factors and suboptimal health among Chinese medical staff: a cross-sectional study.

PubMed

Liang, Ying-Zhi; Chu, Xi; Meng, Shi-Jiao; Zhang, Jie; Wu, Li-Juan; Yan, Yu-Xiang

2018-03-06

The study aimed to develop and validate a model to measure psychosocial factors at work among medical staff in China based on confirmatory factor analysis (CFA). The second aim of the current study was to clarify the association between stress-related psychosocial work factors and suboptimal health status. The cross-sectional study was conducted using clustered sampling method. Xuanwu Hospital, a 3A grade hospital in Beijing. Nine hundred and fourteen medical staff aged over 40 years were sampled. Seven hundred and ninety-seven valid questionnaires were collected and used for further analyses. The sample included 94% of the Han population. The Copenhagen Psychosocial Questionnaire (COPSOQ) and the Suboptimal Health Status Questionnaires-25 were used to assess the psychosocial factors at work and suboptimal health status, respectively. CFA was conducted to establish the evaluating method of COPSOQ. A multivariate logistic regression model was used to estimate the relationship between suboptimal health status and stress-related psychosocial work factors among Chinese medical staff. There was a strong correlation among the five dimensions of COPSOQ based on the first-order factor model. Then, we established two second-order factors including negative and positive psychosocial work stress factors to evaluate psychosocial factors at work, and the second-order factor model fit well. The high score in negative (OR (95% CI)=1.47 (1.34 to 1.62), P<0.001) and positive (OR (95% CI)=0.96 (0.94 to 0.98), P<0.001) psychosocial work factors increased and decreased the risk of suboptimal health, respectively. This relationship remained statistically significant after adjusting for confounders and when using different cut-offs of suboptimal health status. Among medical staff, the second-order factor model was a suitable method to evaluate the COPSOQ. The negative and positive psychosocial work stress factors might be the risk and protective factors of suboptimal health, respectively. Moreover, negative psychosocial work stress was the most associated factor to predict suboptimal health. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Relationship between stress-related psychosocial work factors and suboptimal health among Chinese medical staff: a cross-sectional study

PubMed Central

Meng, Shi-Jiao; Zhang, Jie; Wu, Li-Juan; Yan, Yu-Xiang

2018-01-01

Objectives The study aimed to develop and validate a model to measure psychosocial factors at work among medical staff in China based on confirmatory factor analysis (CFA). The second aim of the current study was to clarify the association between stress-related psychosocial work factors and suboptimal health status. Design The cross-sectional study was conducted using clustered sampling method. Setting Xuanwu Hospital, a 3A grade hospital in Beijing. Participants Nine hundred and fourteen medical staff aged over 40 years were sampled. Seven hundred and ninety-seven valid questionnaires were collected and used for further analyses. The sample included 94% of the Han population. Main outcome measures The Copenhagen Psychosocial Questionnaire (COPSOQ) and the Suboptimal Health Status Questionnaires-25 were used to assess the psychosocial factors at work and suboptimal health status, respectively. CFA was conducted to establish the evaluating method of COPSOQ. A multivariate logistic regression model was used to estimate the relationship between suboptimal health status and stress-related psychosocial work factors among Chinese medical staff. Results There was a strong correlation among the five dimensions of COPSOQ based on the first-order factor model. Then, we established two second-order factors including negative and positive psychosocial work stress factors to evaluate psychosocial factors at work, and the second-order factor model fit well. The high score in negative (OR (95% CI)=1.47 (1.34 to 1.62), P<0.001) and positive (OR (95% CI)=0.96 (0.94 to 0.98), P<0.001) psychosocial work factors increased and decreased the risk of suboptimal health, respectively. This relationship remained statistically significant after adjusting for confounders and when using different cut-offs of suboptimal health status. Conclusions Among medical staff, the second-order factor model was a suitable method to evaluate the COPSOQ. The negative and positive psychosocial work stress factors might be the risk and protective factors of suboptimal health, respectively. Moreover, negative psychosocial work stress was the most associated factor to predict suboptimal health. PMID:29511008

Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study.

PubMed

de Keyser, Catherine E; Leening, Maarten J G; Romio, Silvana A; Jukema, J Wouter; Hofman, Albert; Ikram, M Arfan; Franco, Oscar H; Stijnen, Theo; Stricker, Bruno H

2014-11-01

When studying the causal effect of drug use in observational data, marginal structural modeling (MSM) can be used to adjust for time-dependent confounders that are affected by previous treatment. The objective of this study was to compare traditional Cox proportional hazard models (with and without time-dependent covariates) with MSM to study causal effects of time-dependent drug use. The example of primary prevention of cardiovascular disease (CVD) with statins was examined using up to 17.7 years of follow-up from 4,654 participants of the observational prospective population-based Rotterdam Study. In the MSM model, the weight was based on measurements of established cardiovascular risk factors and co-morbidity. In general, we could not demonstrate important differences in results from the Cox models and MSM. Results from analysis on duration of statin use suggested that substantial residual confounding by indication was not accounted for during the period shortly after statin initiation. In conclusion, although on theoretical grounds MSM is an elegant technique, lack of data on the precise time-dependent confounders, such as indication of treatment or other considerations of the prescribing physician jeopardizes the calculation of valid weights. Confounding remains a hurdle in observational effectiveness research on preventive drugs with a multitude of prescription determinants.

Permethrin Exposure Dosimetry: Biomarkers and Modifiable Factors

DTIC Science & Technology

2017-08-01

metabolite; (F = 16.16, p < 0.0001). This association holds after controlling for known confounders including sex , age, time that uniform was worn...and metabolite concentrations were examined via linear mixed modeling. All models were adjusted for creatinine, age, sex , days in BCT, number of

Testing the Developmental Origins of Health and Disease Hypothesis for Psychopathology Using Family-Based Quasi-Experimental Designs

PubMed Central

D’Onofrio, Brian M.; Class, Quetzal A.; Lahey, Benjamin B.; Larsson, Henrik

2014-01-01

The Developmental Origin of Health and Disease (DOHaD) hypothesis is a broad theoretical framework that emphasizes how early risk factors have a causal influence on psychopathology. Researchers have raised concerns about the causal interpretation of statistical associations between early risk factors and later psychopathology because most existing studies have been unable to rule out the possibility of environmental and genetic confounding. In this paper we illustrate how family-based quasi-experimental designs can test the DOHaD hypothesis by ruling out alternative hypotheses. We review the logic underlying sibling-comparison, co-twin control, offspring of siblings/twins, adoption, and in vitro fertilization designs. We then present results from studies using these designs focused on broad indices of fetal development (low birth weight and gestational age) and a particular teratogen, smoking during pregnancy. The results provide mixed support for the DOHaD hypothesis for psychopathology, illustrating the critical need to use design features that rule out unmeasured confounding. PMID:25364377

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; McCoy, Kathy D; Wullaert, Andy

2018-04-19

Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison.

PubMed

Class, Quetzal A; Rickert, Martin E; Larsson, Henrik; Lichtenstein, Paul; D'Onofrio, Brian M

2014-11-01

It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. In the population, lower birth weight (⩽ 2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems. Royal College of Psychiatrists.

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.

Best (but oft-forgotten) practices: propensity score methods in clinical nutrition research.

PubMed

Ali, M Sanni; Groenwold, Rolf Hh; Klungel, Olaf H

2016-08-01

In observational studies, treatment assignment is a nonrandom process and treatment groups may not be comparable in their baseline characteristics, a phenomenon known as confounding. Propensity score (PS) methods can be used to achieve comparability of treated and nontreated groups in terms of their observed covariates and, as such, control for confounding in estimating treatment effects. In this article, we provide a step-by-step guidance on how to use PS methods. For illustrative purposes, we used simulated data based on an observational study of the relation between oral nutritional supplementation and hospital length of stay. We focused on the key aspects of PS analysis, including covariate selection, PS estimation, covariate balance assessment, treatment effect estimation, and reporting. PS matching, stratification, covariate adjustment, and weighting are discussed. R codes and example data are provided to show the different steps in a PS analysis. © 2016 American Society for Nutrition.

Outcome modelling strategies in epidemiology: traditional methods and basic alternatives

PubMed Central

Greenland, Sander; Daniel, Rhian; Pearce, Neil

2016-01-01

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

Laughter is the Best Medicine? A Cross-Sectional Study of Cardiovascular Disease Among Older Japanese Adults

PubMed Central

Hayashi, Kei; Kawachi, Ichiro; Ohira, Tetsuya; Kondo, Katsunori; Shirai, Kokoro; Kondo, Naoki

2016-01-01

Background We sought to evaluate the associations between frequency of daily laughter with heart disease and stroke among community-dwelling older Japanese women and men. Methods We analyzed cross-sectional data in 20 934 individuals (10 206 men and 10 728 women) aged 65 years or older, who participated in the Japan Gerontological Evaluation Study in 2013. In the mail-in survey, participants provided information on daily frequency of laughter, as well as body mass index, demographic and lifestyle factors, and diagnoses of cardiovascular disease, hyperlipidemia, hypertension, and depression. Results Even after adjustment for hyperlipidemia, hypertension, depression, body mass index, and other risk factors, the prevalence of heart diseases among those who never or almost never laughed was 1.21 (95% CI, −1.03–1.41) times higher than those who reported laughing every day. The adjusted prevalence ratio for stroke was 1.60 (95% CI, 1.24–2.06). Conclusions Daily frequency of laughter is associated with lower prevalence of cardiovascular diseases. The association could not be explained by confounding factors, such as depressive symptoms. PMID:26972732

Combining matched and unmatched control groups in case-control studies.

PubMed

le Cessie, Saskia; Nagelkerke, Nico; Rosendaal, Frits R; van Stralen, Karlijn J; Pomp, Elisabeth R; van Houwelingen, Hans C

2008-11-15

Multiple control groups in case-control studies are used to control for different sources of confounding. For example, cases can be contrasted with matched controls to adjust for multiple genetic or unknown lifestyle factors and simultaneously contrasted with an unmatched population-based control group. Inclusion of different control groups for a single exposure analysis yields several estimates of the odds ratio, all using only part of the data. Here the authors introduce an easy way to combine odds ratios from several case-control analyses with the same cases. The approach is based upon methods used for meta-analysis but takes into account the fact that the same cases are used and that the estimated odds ratios are therefore correlated. Two ways of estimating this correlation are discussed: sandwich methodology and the bootstrap. Confidence intervals for the pooled estimates and a test for checking whether the odds ratios in the separate case-control studies differ significantly are derived. The performance of the method is studied by simulation and by applying the methods to a large study on risk factors for thrombosis, the MEGA Study (1999-2004), wherein cases with first venous thrombosis were included with a matched control group of partners and an unmatched population-based control group.

Maternal age at first birth and offspring criminality: Using the children-of-twins design to test causal hypotheses

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behaviour. It is not clear if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children-of-siblings and children-of-twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant MZ twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association. PMID:23398750

Rumination, anxiety, depressive symptoms and subsequent depression in adolescents at risk for psychopathology: a longitudinal cohort study.

PubMed

Wilkinson, Paul O; Croudace, Tim J; Goodyer, Ian M

2013-10-08

A ruminative style of responding to low mood is associated with subsequent high depressive symptoms and depressive disorder in children, adolescents and adults. Scores on self-report rumination scales correlate strongly with scores on anxiety and depression symptom scales. This may confound any associations between rumination and subsequent depression. Our sample comprised 658 healthy adolescents at elevated risk for psychopathology. This study applied ordinal item (non-linear) factor analysis to pooled items from three self-report questionnaires to explore whether there were separate, but correlated, constructs of rumination, depression and anxiety. It then tested whether rumination independently predicted depressive disorder and depressive symptoms over the subsequent 12 months, after adjusting for confounding variables. We identified a single rumination factor, which was correlated with factors representing cognitive symptoms of depression, somatic symptoms of depression and anxiety symptoms; and one factor representing adaptive responses to low mood. Elevated rumination scores predicted onset of depressive disorders over the subsequent year (p = 0.035), and levels of depressive symptoms 12 months later (p < 0.0005), after adjustment for prior levels of depressive and anxiety symptoms. High rumination predicts onset of depressive disorder in healthy adolescents. Therapy that reduces rumination and increases distraction/problem-solving may reduce onset and relapse rates of depression.

Carrying the pain of abuse: gender-specific findings on the relationship between childhood physical abuse and obesity in adulthood.

PubMed

Fuller-Thomson, Esme; Sinclair, Deborah A; Brennenstuhl, Sarah

2013-01-01

Childhood abuse has been associated with negative adult health outcomes, including obesity. This study sought to investigate the association between childhood physical abuse and adult obesity, while controlling for five clusters of potentially confounding factors: childhood stressors, socioeconomic indicators, marital status, health behaviors, and mental health. Representative data from the 2005 Canadian Community Health Survey were selected. The response rate was approximately 84%. Gender-specific logistic regression analyses determined the association between abuse and obesity, while controlling for age and race and five clusters of potentially confounding factors. Of the 12,590 respondents with complete data, 2,787 were obese and 976 reported physical abuse as a child or adolescent by someone close to them. Among women with childhood physical abuse compared to no abuse, the odds of obesity were 35% higher, even when controlling for age, race, and the five clusters of factors (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 1.09, 1.67). Childhood physical abuse was not associated with adult obesity among men (OR = 1.12; 95% CI = 0.82, 1.53). This study provides one of the first population-based, gender-specific analyses of the association between childhood physical abuse and obesity controlling for a wide range of factors. The gender-specific findings require further exploration.

Maternal age at first birth and offspring criminality: using the children of twins design to test causal hypotheses.

PubMed

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D'Onofrio, Brian M

2013-02-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

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.

The Impact of Quality Assurance Assessment on Diffusion Tensor Imaging Outcomes in a Large-Scale Population-Based Cohort

PubMed Central

Roalf, David R.; Quarmley, Megan; Elliott, Mark A.; Satterthwaite, Theodore D.; Vandekar, Simon N.; Ruparel, Kosha; Gennatas, Efstathios D.; Calkins, Monica E.; Moore, Tyler M.; Hopson, Ryan; Prabhakaran, Karthik; Jackson, Chad T.; Verma, Ragini; Hakonarson, Hakon; Gur, Ruben C.; Gur, Raquel E.

2015-01-01

Background Diffusion tensor imaging (DTI) is applied in investigation of brain biomarkers for neurodevelopmental and neurodegenerative disorders. However, the quality of DTI measurements, like other neuroimaging techniques, is susceptible to several confounding factors (e.g. motion, eddy currents), which have only recently come under scrutiny. These confounds are especially relevant in adolescent samples where data quality may be compromised in ways that confound interpretation of maturation parameters. The current study aims to leverage DTI data from the Philadelphia Neurodevelopmental Cohort (PNC), a sample of 1,601 youths ages of 8–21 who underwent neuroimaging, to: 1) establish quality assurance (QA) metrics for the automatic identification of poor DTI image quality; 2) examine the performance of these QA measures in an external validation sample; 3) document the influence of data quality on developmental patterns of typical DTI metrics. Methods All diffusion-weighted images were acquired on the same scanner. Visual QA was performed on all subjects completing DTI; images were manually categorized as Poor, Good, or Excellent. Four image quality metrics were automatically computed and used to predict manual QA status: Mean voxel intensity outlier count (MEANVOX), Maximum voxel intensity outlier count (MAXVOX), mean relative motion (MOTION) and temporal signal-to-noise ratio (TSNR). Classification accuracy for each metric was calculated as the area under the receiver-operating characteristic curve (AUC). A threshold was generated for each measure that best differentiated visual QA status and applied in a validation sample. The effects of data quality on sensitivity to expected age effects in this developmental sample were then investigated using the traditional MRI diffusion metrics: fractional anisotropy (FA) and mean diffusivity (MD). Finally, our method of QA is compared to DTIPrep. Results TSNR (AUC=0.94) best differentiated Poor data from Good and Excellent data. MAXVOX (AUC=0.88) best differentiated Good from Excellent DTI data. At the optimal threshold, 88% of Poor data and 91% Good/Excellent data were correctly identified. Use of these thresholds on a validation dataset (n=374) indicated high accuracy. In the validation sample 83% of Poor data and 94% of Excellent data was identified using thresholds derived from the training sample. Both FA and MD were affected by the inclusion of poor data in an analysis of age, sex and race in a matched comparison sample. In addition, we show that the inclusion of poor data results in significant attenuation of the correlation between diffusion metrics (FA and MD) and age during a critical neurodevelopmental period. We find higher correspondence between our QA method and DTIPrep for Poor data, but we find our method to be more robust for apparently high-quality images. Conclusion Automated QA of DTI can facilitate large-scale, high-throughput quality assurance by reliably identifying both scanner and subject induced imaging artifacts. The results present a practical example of the confounding effects of artifacts on DTI analysis in a large population-based sample, and suggest that estimates of data quality should not only be reported but also accounted for in data analysis, especially in studies of development. PMID:26520775

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth

PubMed Central

Feldstein Ewing, Sarah W.; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

Background A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. Methods For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Results Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Conclusions Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain. PMID:26958467

Comparative risk of microalbuminuria and proteinuria in UK residents of south Asian and white European ethnic background with type 2 diabetes: a report from UKADS.

PubMed

Raymond, Neil T; Paul O'Hare, J; Bellary, Srikanth; Kumar, Sudhesh; Jones, Alan; Barnett, Anthony H

2011-11-01

This study investigated and compared the prevalence of microalbuminuria and overt proteinuria and their determinants in a cohort of UK resident patients of white European or south Asian ethnicity with type 2 diabetes mellitus. A total of 1978 patients, comprising 1486 of south Asian and 492 of white European ethnicity, in 25 general practices in Coventry and Birmingham inner city areas in England were studied in a cross-sectional study. Demographic and risk factor data were collected and presence of microalbuminuria and overt proteinuria assessed. ISRCTN 38297969. Prevalences of microalbuminuria and overt proteinuria. Urinary albumin:creatinine measurements were available for 1852 (94%) patients. The south Asian group had a lower prevalence of microalbuminuria, 19% vs. 23% and a higher prevalence of overt proteinuria, 8% vs. 3%, χ(2) = 15.85, 2df, P = 0.0004. In multiple logistic regression models, adjusted for confounding factors, significantly increased risk for the south Asian vs. white European patients for overt proteinuria was shown; OR (95% CI) 2.17 (1.05, 4.49), P = 0.0365. For microalbuminuria, an interaction effect for ethnicity and duration of diabetes suggested that risk for south Asian patients was lower in early years following diagnosis; OR for SA vs. WH at durations 0 and 1 year were 0.56 (0.37, 0.86) and 0.59 (0.39, 0.89) respectively. After 20 years' duration, OR = 1.40 (0.63, 3.08). Comparability of ethnicity defined groups; statistical methods controlled for differences between groups, but residual confounding may remain. Analyses are based on a single measure of albumin:creatinine ratio. There were significant differences between ethnicity groups in risk factor profiles and microalbuminuria and overt proteinuria outcomes. Whilst south Asian patients had no excess risk of microalbuminuria, the risk of overt proteinuria was elevated significantly, which might be explained by faster progression of renal dysfunction in patients of south Asian ethnicity.

Total and Abdominal Adiposity and Hypertension in Indigenous Women in Midwest Brazil

PubMed Central

Lima, Rosangela Costa; de Souza, Maria Cristina Corrêa

2016-01-01

Background Obesity is a major risk factor for hypertension, and abdominal fat in particular has been more strongly associated with cardiovascular diseases and its prevalence has increased in Brazilian indigenous populations. Objective The objective of this study was to estimate the prevalence of hypertension among indigenous women and its association with total and abdominal obesity after adjustment for confounding factors. Methods This cross-sectional study evaluated indigenous non-pregnant women aged 20–59 years living in two villages of the indigenous reserve of Dourados, state of Mato Grosso do Sul, Brazil. Data were collected by trained interviewers. Households were visited and were selected by simple random sampling using SPSS software version 21. The casting of lots was performed from a list of households located on a map of villages. To locate the selected households, a Global Positioning System device was used. A questionnaire was used to obtain data on socio-demographic, lifestyle and health-related variables and to obtain anthropometric data on weight, height, and waist circumference (WC). Blood pressure was measured twice during home visits. Results Data were collected between June and October 2013 with 362 women. Most of them were aged <40 years (66.3%) and had low educational level (≤4 years of schooling, 82.0%), had overweight/obesity (74.0%), WC ≥80 cm (83.7%), and family history of hypertension (60.5%). The prevalence of hypertension was 42.0% (CI 95%: 37.0–47.2). In the multivariable analysis, respondents with WC 80–87 cm and ≥88 cm showed approximately 2 times higher prevalence rates of hypertension compared with those with WC <80 cm after adjusting for confounding factors. There was no association between body mass index (BMI) and hypertension in this study. Conclusions The overall prevalence of hypertension was high and associated only with abdominal adiposity but not with BMI. PMID:27294870

The role of environmental factors for the onset of restricted mobility outside the home among older adults with osteoarthritis: a prospective cohort study

PubMed Central

Rantakokko, Merja; Wilkie, Ross

2017-01-01

Objectives The study examines how environmental factors contribute to the onset of restricted mobility outside the home among older adults with osteoarthritis. Methods This is a prospective cohort study of adults aged 50 years and older with osteoarthritis (n=1802). Logistic regression tested the association between the onset of restricted mobility outside the home and health, sociodemographic and perceived environmental barriers (hills and steep slopes, inaccessible public buildings, poor pavement condition, lack of access to public parks or sport facilities, heavy traffic or speeding cars and poor weather). The potential moderating role of environmental barriers on the association between health factors and onset was examined using interaction terms and stratified analysis. Results Of 1802 participants, 13.5% (n=243) reported the onset of restricted mobility outside the home at 3-year follow-up. Walking disability, anxiety, depression, cognitive impairment and obesity and all environmental barriers were associated with onset after adjustment for confounders. Environmental barriers had an added contribution to the effect of the health conditions on onset of restricted mobility, which was attenuated when adjusted for confounders. The added contribution remained only for walking disability and the presence of hills and steep slopes; in the presence of both, the association with onset of restricted mobility was stronger (OR 7.66, 95% CI 4.64 to 12.64) than in the presence of walking disability (3.60, 2.43 to 5.32) or the presence of hills and steep slopes alone (4.55, 2.89 to 7.16). Conclusion For older adults with osteoarthritis, environmental barriers are associated and add a contribution to that of morbidities and walking disability on the onset of restricted mobility outside the home. Awareness of environmental barriers is important when aiming to maintain mobility and activities outside the home despite health conditions in older adults. PMID:28667194

A powerful and efficient set test for genetic markers that handles confounders

PubMed Central

Listgarten, Jennifer; Lippert, Christoph; Kang, Eun Yong; Xiang, Jing; Kadie, Carl M.; Heckerman, David

2013-01-01

Motivation: Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger datasets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects—one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured Genetic Analysis Workshop 14 data demonstrates that our method successfully corrects for population structure and family relatedness, whereas application of our method to a 15 000 individual Crohn’s disease case–control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http://mscompbio.codeplex.com. Contact: jennl@microsoft.com or lippert@microsoft.com or heckerma@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23599503

Clinical Research Methodology 2: Observational Clinical Research.

PubMed

Sessler, Daniel I; Imrey, Peter B

2015-10-01

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

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

PubMed

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

2014-06-01

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

Directly Observed Therapy Reduces Tuberculosis-Specific Mortality: A Population-Based Follow-Up Study in Taipei, Taiwan

PubMed Central

Yen, Yung-Feng; Yen, Muh-Yong; Lin, Yi-Ping; Shih, Hsiu-Chen; Li, Lan-Huei; Chou, Pesus; Deng, Chung-Yeh

2013-01-01

Objectives To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB). Methods All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006–2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome. Results Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30–0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65–79 and ≥80 years vs. 18–49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk. Conclusions DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality. PMID:24278152

Formaldehyde Exposure and Lower Respiratory Infections in Infants: Findings from the PARIS Cohort Study

PubMed Central

Roda, Célina; Kousignian, Isabelle; Guihenneuc-Jouyaux, Chantal; Dassonville, Claire; Nicolis, Ioannis; Just, Jocelyne

2011-01-01

Background: Certain chemical pollutants can exacerbate lower respiratory tract infections (LRIs), a common childhood ailment. Although formaldehyde (FA) is one of the most common air pollutants found in indoor environments, its impact on infant health is uncertain. Objective: Our aim was to determine the impact of FA exposure on the LRI incidence during the first year of life of infants from the Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort. Methods: FA was measured in a random sample of 196 infants’ dwellings, and exposure to this pollutant was estimated for 2,940 infants using predictive models based on measurements and data about potential determinants of FA levels. Health data were collected from parents by regular self-administered questionnaires. We used multivariate logistic regressions to estimate associations between FA exposure and the occurrence of LRI and wheezy LRI (wLRI), adjusting for potential confounders/risk factors. Results: During the first year of life, 45.8% of infants had at least one LRI, and LRI occurred simultaneously with wheezing in 48.7% of cases. The FA predictive models correctly classified 70% of dwellings as having high or low exposure, and we estimated that 43.3% of infants were exposed throughout the first year to levels of FA > 19.5 µg/m3. FA exposure was significantly associated with LRI and wLRI before and after adjustment for known LRI risk factors/confounders. For an interquartile increase in FA levels (12.4 μg/m3), we estimated a 32% [95% confidence interval (CI): 11, 55] and 41% (95% CI: 14, 74) increase in the incidence of LRI and wLRI, respectively. Conclusion: The findings of this study suggest that infants exposed to FA at an early age have an increased incidence of LRI. PMID:21810553

Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations.

PubMed

Shrestha, Saurav; Hirvonen, Jussi; Hines, Christina S; Henter, Ioline D; Svenningsson, Per; Pike, Victor W; Innis, Robert B

2012-02-15

The serotonin-1A (5-HT(1A)) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT(1A) receptor density, two reported no change, and two reported increased 5-HT(1A) receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the 'gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter - like P-gp - at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT(1A) receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis. Published by Elsevier Inc.

Restless legs syndrome status as a predictor for lower physical function

PubMed Central

Zhang, Chunbai; Li, Yanping; Malhotra, Atul; Ning, Yi

2014-01-01

Objective: To examine the potential long-term impact of restless legs syndrome (RLS) and other common sleep complaints on subsequent physical function (PF), we conducted a longitudinal analysis of 12,556 men in the Health Professionals Follow-up Study. Methods: We used a set of questions recommended by the International RLS Study Group to assess RLS in 2002. We asked questions regarding other sleep complaints—insomnia, sleep fragmentation, and excessive daytime sleepiness—in 2004. We used the Physical Function (PF-10) survey of the Short Form–36 Health Survey to characterize PF in 1996 and 2008. We examined the 2008 PF-10 scores across categories of baseline RLS (2002), adjusted for age, 1996 PF-10 score, and other potential confounders. Results: The participants with RLS at baseline had significantly lower PF-10 score 6 years later than those without RLS (mean difference = −2.32, p = 0.01), after adjusting for potential confounders. The magnitude of difference in PF-10 score for RLS symptoms ≥15 times/month vs no RLS was more than that of a 5-year increase of age or moderate amount of smoking. Having daily daytime sleepiness and sleep duration ≥9 hours/day were associated with lower mean PF value than not having these symptoms (p < 0.05 for both). Conclusions: RLS and other sleep complaints are associated with lower PF. Our findings need to be replicated by more longitudinal studies including women and populations of other social and cultural backgrounds. It is important to understand whether RLS is an independent risk factor or a marker for other unknown risk factors for disability. PMID:24598708

Witness of Intimate Partner Violence in Childhood and Perpetration of Intimate Partner Violence in Adulthood

PubMed Central

Roberts, Andrea L.; Gilman, Stephen E.; Fitzmaurice, Garrett; Decker, Michele R.; Koenen, Karestan C.

2011-01-01

Background At least half a million women are victims of intimate partner violence in the United States annually, resulting in substantial harm. However, the etiology of violence to intimate partners is not well understood. Witnessing such violence in childhood has been proposed as a principal cause of adulthood perpetration, yet it remains unknown whether the association between witnessing intimate partner violence and adulthood perpetration is causal. Method We conducted a propensity-score analysis of intimate partner violence perpetration to determine whether childhood witnessing is associated with perpetration in adulthood, independent of a wide range of potential confounding variables, and therefore might be a causal factor. We used data from 14,564 U.S. men ages 20 and older from the 2004–2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions. Results Nearly 4% of men reported violent behavior toward an intimate partner in the past year. In unadjusted models, we found a strong association between childhood witnessing of intimate partner violence and adulthood perpetration (for witnessing any intimate partner violence, risk ratio [RR] = 2.6 [95% confidence interval = 2.1–3.2]; for witnessing frequent or serious violence, 3.0 [2.3–3.9]). In propensity-score models, the association was substantially attenuated (for witnessing any intimate partner violence, adjusted RR = 1.6 [1.2–2.0]; for witnessing frequent or serious violence, 1.6 [1.2–2.3]). Conclusions Men who witness intimate partner violence in childhood are more likely to commit such acts in adulthood, compared with men who are otherwise similar with respect to a large range of potential confounders. Etiological models of intimate partner violence perpetration should consider a constellation of childhood factors. PMID:20811285

SENSE OF CONTROL AND SELF-REPORTED HEALTH IN A POPULATION-BASED SAMPLE OF OLDER AMERICANS: ASSESSMENT OF POTENTIAL CONFOUNDING BY AFFECT, PERSONALITY, AND SOCIAL SUPPORT

PubMed Central

Ward, Michael M.

2012-01-01

Background Sense of control has been linked to improved health outcomes, but it is unclear if this association is independent of other psychosocial factors. Purpose To test the strength of association between sense of control and self-reported health after adjustment for positive and negative affect, “Big 5” personality factors, and social support. Method Data on sense of control (measured by personal mastery, perceived constraints, and a health-specific rating of control), affect, personality, social support, and two measures of self-reported health (global rating of fair or poor health, and presence of functional limitations) were obtained on 6891 participants in the Health and Retirement Study, a population-based survey of older Americans. The cross-sectional association between sense of control measures and each measure of self-reported health was tested in hierarchical logistic regression models, before and after adjustment for affect, personality, and social support. Results Participants with higher personal mastery were less likely to report fair/poor health (odds ratio 0.76 per 1-point increase) while those with higher perceived constraints were more likely to report fair/poor health (odds ratio 1.37 per 1-point increase). Associations remained after adjustment for affect, but adjustment for affect attenuated the association of personal mastery by 37% and of perceived constraints by 67%. Further adjustment for personality and social support did not alter the strength of association. Findings were similar for the health-specific rating of control, and for associations with functional limitations. Conclusions Sense of control is associated with self-reported health in older Americans, but this association is partly confounded by affect. PMID:22282403

Social participation and coronary heart disease risk in a large prospective study of UK women

PubMed Central

Balkwill, Angela; Canoy, Dexter; Reeves, Gillian K; Green, Jane; Beral, Valerie; Cairns, Benjamin J

2015-01-01

Background Participation in social activities is thought to prevent heart disease, but evidence is inconclusive. Design We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women. Methods Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities. Results After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81–0.86), but changed to 1.06 (99% confidence interval 1.02–1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations. Conclusions Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants. PMID:26416995

A Prospective Study of Different Types of Dietary Fiber and Risk of Cardiovascular Disease: Tehran Lipid and Glucose Study

PubMed Central

Mirmiran, Parvin; Bahadoran, Zahra; Khalili Moghadam, Sajad; Zadeh Vakili, Azita; Azizi, Fereidoun

2016-01-01

Background and aim: This study was designed to examine the hypothesis that dietary of intake different types of fiber could modify the risk of cardiovascular disease (CVD) in a large prospective cohort among Iranian adults. Methods: In 2006–2008, we used a validated food frequency questionnaire to assess dietary fiber intake among 2295 health professionals with no previous history of heart disease. Subjects were subsequently followed until 2012 for incidence of CVD events. Multivariate Cox proportional hazard regression models, adjusted for potential confounders were used to estimate the risk of CVD across tertiles of total dietary fiber and different types of fiber. Linear regression models were also used to indicate the association of dietary fiber intakes with changes of cardiovascular risk factors during the follow-up. Results: Mean age of participants (42.8% men) was 38.2 ± 13.4, at baseline. Mean (SD) dietary intake of total fiber was 23.4 (8.9) g/day. After adjustment for cardiovascular risk score and dietary confounders, a significant inverse association was observed between intakes of total, soluble and insoluble dietary fiber and CVD risk, in the highest compared to the lowest tertiles (HR = 0.39, 95% CI = 0.18–0.83, HR = 0.19, 95% CI = 0.09–0.41, and HR = 0.31, 95% CI = 0.14–0.69, respectively). Inverse relations were observed between risk of CVD and dietary fiber from legumes, fruits and vegetables; however, dietary fiber intake from grain and nut sources was not related to risk of CVD. Conclusion: Our findings confirmed that higher intakes of dietary fiber from different sources is associated with CVD events and modify its major risk-related factors. PMID:27827978

Register-based data of psychosocial working conditions and occupational groups as predictors of disability pension due to musculoskeletal diagnoses: a prospective cohort study of 24 543 Swedish twins

PubMed Central

2013-01-01

Background Occupations and psychosocial working conditions have rarely been investigated as predictors of disability pension in population-based samples. This study investigated how occupational groups and psychosocial working conditions are associated with future disability pension due to musculoskeletal diagnoses, accounting for familial factors in the associations. Methods A sample of 24 543 same-sex Swedish twin individuals was followed from 1993 to 2008 using nationwide registries. Baseline data on occupations were categorized into eight sector-defined occupational groups. These were further used to reflect psychosocial working conditions by applying the job strain scores of a Job Exposure Matrix. Cox proportional hazard ratios (HR) were estimated. Results During the 12-year (average) follow-up, 7% of the sample was granted disability pension due to musculoskeletal diagnoses. Workers in health care and social work; agriculture, forestry and fishing; transportation; production and mining; and the service and military work sectors were two to three times more likely to receive a disability pension than those in the administration and management sector. Each single unit decrease in job demands and each single unit increase in job control and social support significantly predicted disability pension. Individuals with high work strain or an active job had a lower hazard ratio of disability pension, whereas a passive job predicted a significantly higher hazard ratio. Accounting for familial confounding did not alter these results. Conclusion Occupational groups and psychosocial working conditions seem to be independent of familial confounding, and hence represent risk factors for disability pension due to musculoskeletal diagnoses. This means that preventive measures in these sector-defined occupational groups and specific psychosocial working conditions might prevent disability pension due to musculoskeletal diagnoses. PMID:24040914

Season and preterm birth in Norway: A cautionary tale

PubMed Central

Weinberg, Clarice R; Shi, Min; DeRoo, Lisa A; Basso, Olga; Skjærven, Rolv

2015-01-01

Background: Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. Methods: We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2 321 652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. Results: Naïve analysis of preterm rates across days of birth shows compelling evidence for seasonality (P < 10−152). However, the reconstructed numbers of conceptions also vary with season (P < 10−307), confounding results by inducing seasonal variation in the age distribution of the fetal population at risk. When we instead properly treat fetuses as the individuals at risk, restrict analysis to pregnancies with relatively accurate ultrasound-based assessment of gestational age (available since 1998) and adjust for socio-demographic factors and maternal smoking, we find modest effects of both time of year of conception and time of year at risk, with peaks for early preterm near early January and early July. Conclusions: Analyses of seasonal effects on preterm birth are demonstrably vulnerable to confounding by seasonality of conception, measurement error in conception dating, and socio-demographic factors. The seasonal variation based on fetuses reveals two peaks for early preterm, coinciding with New Year’s Day and the early July beginning of Norway’s summer break, and may simply reflect a holiday-related pattern of unintended conception. PMID:26045507

AfroColombian ethnicity, a paradoxical protective factor against Dengue

PubMed Central

Alzate, Alberto; Martínez Romero, Héctor Jairo; Concha-Eastman, Alberto Ignacio

2016-01-01

Introduction: Dengue is a priority public health problem. During epidemics in Cuba and Haiti, ethnic African descendant population had lower risk of dengue, and the ethnic factor was proposed as a protective one. Objective: To determine the relation between the Dengue's cumulative incidence and the Afro-Colombian proportion in communities of Cali, during the epidemic of 2013. Methods: This study was conducted in Cali, Colombia. The design was ecological, using information from the National Census 2005 projected to 2013, from the National Administrative Department of Statistics (DANE), and the National Epidemiological Surveillance System. It was obtained the Pearson´s correlation coefficient between cumulative incidence and the proportion of Afro-Colombian population by communities. Additionally, the cumulative incidences of dengue were evaluated in two zones with different proportion of Afro-Colombian population. The association was also evaluated for aggregation bias, confounding by social variables, and interaction by area of ​​residence. Results: Dengue´s cumulative incidence was significantly lower for Afro-Colombians regardless of the proportion of Afro-Colombian population in the area of residence. The relative risk of dengue between non-Afro-Colombians and Afro-Colombians was 9.4 (95% CI=8.4-10.6) in zones with high proportion of Afro-Colombian population, while the relative risk of dengue was 4.0 (95% CI :3.6 - 4.4) in the zone with lower proportion of Afro-Colombian population. There was no evidence of aggregation bias or confounding in the association by social variables. Conclusions: The Afro-Colombian population had a significantly lower risk of getting dengue and its complications, compared with the non-Afro-Colombian population. The non-Afro-Colombian populations living in areas with a high proportion of Afro-Colombians increase their risk of dengue more than double, suggesting an asymptomatic viremic environment. PMID:27821892

Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations

PubMed Central

Shrestha, Saurav; Hirvonen, Jussi; Hines, Christina S.; Henter, Ioline; Svenningsson, Per; Pike, Victor W.; Innis, Robert B.

2011-01-01

The serotonin-1A (5-HT1A) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT1A receptor density, two reported no change, and two reported increased 5-HT1A receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the `gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter—like P-gp—at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT1A receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis. PMID:22155042

Fetal environment and early age at natural menopause in a British birth cohort study

PubMed Central

Tom, Sarah E.; Cooper, Rachel; Kuh, Diana; Guralnik, Jack M.; Hardy, Rebecca; Power, Chris

2010-01-01

BACKGROUND Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study. METHODS Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44–45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44–45 years, with and without adjustments for confounding factors. RESULTS There was a U-shaped association between birthweight and menopausal status at 44–45 years: women at either extremes of birthweight (<2.5 and ≥4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0–3.49 kg [odds ratio (OR) = 1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44–45 years (OR for fastest quarter versus second fastest quarter = 1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives. CONCLUSIONS These findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further. PMID:20047935

Medical students perception of test anxiety triggered by different assessment modalities.

PubMed

Guraya, Salman Y; Guraya, Shaista S; Habib, Fawzia; AlQuiliti, Khalid W; Khoshhal, Khalid I

2018-05-06

Test anxiety is well known among medical students. However, little is known about test anxiety produced by different components of exam individually. This study aimed to stratify varying levels of test anxiety provoked by each exam modality and to explore the students perceptions about confounding factors. A self-administered questionnaire was administered to medical students. The instrument contained four main themes; lifestyle, psychological and specific factors of information needs, learning styles, and perceived difficulty level of each assessment tool. A highest test anxiety score of 5 was ranked for "not scheduling available time" and "insufficient exercise" by 28.8 and 28.3% students, respectively. For "irrational thoughts about exam" and "fear to fail", a highest test anxiety score of 5 was scored by 28.8 and 25.7% students, respectively. The highest total anxiety score of 1255 was recorded for long case exam, followed by 975 for examiner-based objective structured clinical examination. Excessive course load and course not well covered by faculty were thought to be the main confounding factors. The examiner-based assessment modalities induced high test anxiety. Faculty is urged to cover core contents within stipulated time and to rigorously reform and update existing curricula to prepare relevant course material.

On the Influence of Confounding Factors in Multisite Brain Morphometry Studies of Developmental Pathologies: Application to Autism Spectrum Disorder.

PubMed

Auzias, G; Takerkart, S; Deruelle, C

2016-05-01

Pooling data acquired on different MR scanners is a commonly used practice to increase the statistical power of studies based on MRI-derived measurements. Such studies are very appealing since they should make it possible to detect more subtle effects related to pathologies. However, the influence of confounds introduced by scanner-related variations remains unclear. When studying brain morphometry descriptors, it is crucial to investigate whether scanner-induced errors can exceed the effect of the disease itself. More specifically, in the context of developmental pathologies such as autism spectrum disorders (ASD), it is essential to evaluate the influence of the scanner on age-related effects. In this paper, we studied a dataset composed of 159 anatomical MR images pooled from three different scanners, including 75 ASD patients and 84 healthy controls. We quantitatively assessed the effects of the age, pathology, and scanner factors on cortical thickness measurements. Our results indicate that scan pooling from different sites would be less fruitful in some cortical regions than in others. Although the effect of age is consistent across scanners, the interaction between the age and scanner factors is important and significant in some specific cortical areas.

Sperm studies in anesthesiologists

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

Wyrobek, A.J.; Brodsky, J.; Gordon, l.

1981-11-01

Semen samples were collected from 46 anesthesiologists each of whom had worked a minimum of one year in hospital operating rooms ventilated with modern gas-scavenging devices. Samples collected from 26 beginning residents in anesthesiology served as controls. Concentrations of sperm and percentage of sperm having abnormal head shapes were determined for each sample. No significant differences were found between anesthesiologists and beginning residents. Limiting the analyses to men having no confounding factors (varicocele, recent illness, medications, heavy smoking, frequent sauna use) did not change the results. The sperm concentration and morphology in 13 men did not change signficantly after onemore » year of exposure to anesthetic gases. However, the group of men who had one or more confounding factors (excluding exposure to anesthetic gases) showed significantly higher percentages of sperm abnormalities than did the group of men without such factors. These results suggest that limited exposure to anesthetic gases does not significantly affect sperm production as judged by changes in sperm concentration and morphology. These data are reassuring, but since the hospitals surveyed used modern gas-scavenging devices, men who are occupationally exposed to anesthetic gases without this protection should be studied for fuller assessment of the possible human spermatotoxic effects.« less

In plastico: laboratory material newness affects growth and reproduction of Daphnia magna reared in 50-ml polypropylene tubes

PubMed Central

Cuhra, Marek; Bøhn, Thomas; Cuhra, Petr

2017-01-01

Plastic laboratory materials are found to affect vital parameters of the waterflea Daphnia magna. The main responsible factor is defined as “newness” of the materials. Juvenile D. magna were raised individually in; a) new laboratory-standard 50 ml polypropylene tubes, and; b) identical tubes which had been washed and aerated for several weeks. Newness had significant effects on growth and fecundity of D. magna. New tubes caused delayed maturation, reduced reproduction and reduced growth when compared to washed and re-used tubes of the same commercial brand. The findings indicate that newness of tubes has inhibiting or toxic effects on D. magna. Often laboratory plastics are intended for single-use due to sterility demands. Newness might be an important confounding factor in research results and should not be disregarded. Disposable plastic utensils may come with a seemingly ignored cost and induce adverse effects in biological test-organisms and systems. The presented findings accentuate continued need for general awareness concerning confounding factors stemming from material laboratory environment. Based on the present findings the authors suggest that plastics intended for use in sensitive research may need to be washed and aerated prior to use. PMID:28425469

An Examination of the Relationship between Motor Coordination and Executive Functions in Adolescents

ERIC Educational Resources Information Center

Rigoli, Daniela; Piek, Jan P.; Kane, Robert; Oosterlaan, Jaap

2012-01-01

Aim: Research suggests important links between motor coordination and executive functions. The current study examined whether motor coordination predicts working memory, inhibition, and switching performance, extending previous research by accounting for attention-deficit-hyperactivity disorder (ADHD) symptomatology and other confounding factors,…

A TIME SERIES ANALYSIS OF AIR POLLUTION AND PRETERM BIRTH IN PENNSYLVANIA, 1997-2001

EPA Science Inventory

Introduction: Small increases in risk for preterm delivery in relation to air pollution have been reported, but prior investigations may have inadequately controlled for individual factors, such as maternal smoking. To eliminate confounding by known and unknown individual risk f...

Effects of Disturbance-induced trauma on foraging by subterranean termites (Isoptera: Rhinotermitidae)

Treesearch

R. J. Woodrow; T. G. Shelton; R. J. Oshiro; J. K. Grace; T. L. Wagner

2008-01-01

Toxicant baiting systems are effective at population suppression against both the Formosan subterranean termite, Coptotermes formosanus Shiraki, and the Eastern subterranean termite, Reticulitermes flavipes (Kollar). However, trap shyness (i.e., station abandonment) is often quoted as a confounding factor affecting their success....

IDENTIFICATION AND INTERPRETATION OF DEVELOPMENTAL NEUROTOXICITY EFFECTS: A REPORT FROM THE ILSI RESEARCH FOUNDATION/RISK SCIENCE INSTITUTE EXPERT WORKING GROUP ON NEURODEVELOPMENTAL ENDPOINTS

EPA Science Inventory

The reliable detection, measurement, and interpretation of treatment-related developmental neurotoxicity (DNT) effects depend on appropriate study design and execution, using scientifically established methodologies, with appropriate controls to minimize confounding factors. App...

Urinary excretion of mutagens in coke oven workers.

PubMed

Clonfero, E; Granella, M; Marchioro, M; Barra, E L; Nardini, B; Ferri, G; Foà, V

1995-03-01

The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). Multiple regression analysis showed that the mutagenic potency of urinary extracts of coke oven workers depended on exposure to PAHs, tobacco smoking habits, and consumption of fried, grilled or barbecued meat. Increased urinary mutagenic activity strengthens epidemiological evidence of the increased risk of renal and urinary tract tumours in these workers. The presence of mutagenic metabolites in urine as a result of occupational exposure to PAH may be demonstrated only by using highly sensitive techniques for assessing urinary mutagenic activity in studies which include careful checking of the main confounding factors.

Studying neuroanatomy using MRI.

PubMed

Lerch, Jason P; van der Kouwe, André J W; Raznahan, Armin; Paus, Tomáš; Johansen-Berg, Heidi; Miller, Karla L; Smith, Stephen M; Fischl, Bruce; Sotiropoulos, Stamatios N

2017-02-23

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging and disease. Developments in MRI acquisition, image processing and data modeling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and for inferring microstructural properties; we also describe key artifacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, although methods need to improve and caution is required in interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works.

An investigation into the relationship between age and physiological function in highly active older adults

PubMed Central

Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

2015-01-01

Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. Key Points The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55–79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. PMID:25565071

An investigation into the relationship between age and physiological function in highly active older adults.

PubMed

Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

2015-02-01

The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55-79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. V̇O2max was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55-79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption (V̇O2max) showed the closest association with age (r = -0.443 to -0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

When Work is Related to Disease, What Establishes Evidence for a Causal Relation?

PubMed

Verbeek, Jos

2012-06-01

Establishing a causal relationship between factors at work and disease is difficult for occupational physicians and researchers. This paper seeks to provide arguments for the judgement of evidence of causality in observational studies that relate work factors to disease. I derived criteria for the judgement of evidence of causality from the following sources: the criteria list of Hill, the approach by Rothman, the methods used by International Agency for Research on Cancer (IARC), and methods used by epidemiologists. The criteria are applied to two cases of putative occupational diseases; breast cancer caused by shift work and aerotoxic syndrome. Only three of the Hill criteria can be applied to an actual study. Rothman stresses the importance of confounding and alternative explanations than the putative cause. IARC closely follows Hill, but they also incorporate other than epidemiological evidence. Applied to shift work and breast cancer, these results have found moderate evidence for a causal relationship, but applied to the aerotoxic syndrome, there is an absence of evidence of causality. There are no ready to use algorithms for judgement of evidence of causality. Criteria from different sources lead to similar results and can make a conclusion of causality more or less likely.

When Work is Related to Disease, What Establishes Evidence for a Causal Relation?

PubMed Central

2012-01-01

Establishing a causal relationship between factors at work and disease is difficult for occupational physicians and researchers. This paper seeks to provide arguments for the judgement of evidence of causality in observational studies that relate work factors to disease. I derived criteria for the judgement of evidence of causality from the following sources: the criteria list of Hill, the approach by Rothman, the methods used by International Agency for Research on Cancer (IARC), and methods used by epidemiologists. The criteria are applied to two cases of putative occupational diseases; breast cancer caused by shift work and aerotoxic syndrome. Only three of the Hill criteria can be applied to an actual study. Rothman stresses the importance of confounding and alternative explanations than the putative cause. IARC closely follows Hill, but they also incorporate other than epidemiological evidence. Applied to shift work and breast cancer, these results have found moderate evidence for a causal relationship, but applied to the aerotoxic syndrome, there is an absence of evidence of causality. There are no ready to use algorithms for judgement of evidence of causality. Criteria from different sources lead to similar results and can make a conclusion of causality more or less likely. PMID:22993715

Detecting macroecological patterns in bacterial communities across independent studies of global soils.

PubMed

Ramirez, Kelly S; Knight, Christopher G; de Hollander, Mattias; Brearley, Francis Q; Constantinides, Bede; Cotton, Anne; Creer, Si; Crowther, Thomas W; Davison, John; Delgado-Baquerizo, Manuel; Dorrepaal, Ellen; Elliott, David R; Fox, Graeme; Griffiths, Robert I; Hale, Chris; Hartman, Kyle; Houlden, Ashley; Jones, David L; Krab, Eveline J; Maestre, Fernando T; McGuire, Krista L; Monteux, Sylvain; Orr, Caroline H; van der Putten, Wim H; Roberts, Ian S; Robinson, David A; Rocca, Jennifer D; Rowntree, Jennifer; Schlaeppi, Klaus; Shepherd, Matthew; Singh, Brajesh K; Straathof, Angela L; Bhatnagar, Jennifer M; Thion, Cécile; van der Heijden, Marcel G A; de Vries, Franciska T

2018-02-01

The emergence of high-throughput DNA sequencing methods provides unprecedented opportunities to further unravel bacterial biodiversity and its worldwide role from human health to ecosystem functioning. However, despite the abundance of sequencing studies, combining data from multiple individual studies to address macroecological questions of bacterial diversity remains methodically challenging and plagued with biases. Here, using a machine-learning approach that accounts for differences among studies and complex interactions among taxa, we merge 30 independent bacterial data sets comprising 1,998 soil samples from 21 countries. Whereas previous meta-analysis efforts have focused on bacterial diversity measures or abundances of major taxa, we show that disparate amplicon sequence data can be combined at the taxonomy-based level to assess bacterial community structure. We find that rarer taxa are more important for structuring soil communities than abundant taxa, and that these rarer taxa are better predictors of community structure than environmental factors, which are often confounded across studies. We conclude that combining data from independent studies can be used to explore bacterial community dynamics, identify potential 'indicator' taxa with an important role in structuring communities, and propose hypotheses on the factors that shape bacterial biogeography that have been overlooked in the past.

Is infant feeding pattern associated with father's quality of life?

PubMed

Chen, Yi Chun; Chie, Wei-Chu; Chang, Pei-Jen; Chuang, Chao-Hua; Lin, Yu-Hsuan; Lin, Shio-Jean; Chen, Pau-Chung

2010-12-01

The aim of this study was to compare the health-related quality of life of fathers under different infant feeding type scenarios. The Medical Outcomes Study 36-item Short-Form was used to measure the health-related quality of life of 1,699 fathers, and the scores were used to look for associations with different infant feeding methods. Multivariable linear regression analysis was used to explore the contribution of the other potential related factors on fathers' quality of life. After controlling for confounding factors, fathers whose infants were ever being breast-fed reported lower scores than fathers whose infants were bottle-fed. Except for the infant feeding pattern, having a job, higher family income, and being the major caregiver were positively related to the father's quality of life. Fathers may not benefit during breast-feeding process. Because fathers' involvement plays an important role in the success of breast-feeding, the development of interventions that enable fathers to support their breast-feeding partner is very important.

Regional socioeconomic disparities in outcomes for workers with low back pain in the United States

PubMed Central

Shraim, Mujahed; Cifuentes, Manuel; Willetts, Joanna L.; Marucci‐Wellman, Helen R.

2017-01-01

Background Although regional socioeconomic (SE) factors have been associated with worse health outcomes, prior studies have not addressed important confounders or work disability. Methods A national sample of 59 360 workers’ compensation (WC) cases to evaluate impact of regional SE factors on medical costs and length of disability (LOD) in occupational low back pain (LBP). Results Lower neighborhood median household incomes (MHI) and higher state unemployment rates were associated with longer LOD. Medical costs were lower in states with more workers receiving Social Security Disability, and in areas with lower MHI, but this varied in magnitude and direction among neighborhoods. Medical costs were higher in more urban, more racially diverse, and lower education neighborhoods. Conclusions Regional SE disparities in medical costs and LOD occur even when health insurance, health care availability, and indemnity benefits are similar. Results suggest opportunities to improve care and disability outcomes through targeted health care and disability interventions. PMID:28370474

The age and other factors in the evaluation of compliance with nasal continuous positive airway pressure for obstructive sleep apnea syndrome. A Cox's proportional hazard analysis.

PubMed

Pelletier-Fleury, N; Rakotonanahary, D; Fleury, B

2001-05-01

Objective: To elucidate the predictive role of age and other pre-treatment, putative confounding factors on compliance with nasal continuous positive airway pressure (nCPAP) therapy.Patients and methods: This study was designed as a prospective cohort study in the setting of a sleep laboratory in a teaching hospital at Saint Antoine, Paris. One hundred and sixty-three patients referred to the sleep laboratory with complaints of snoring and excessive daytime sleepiness for whom nCPAP had been prescribed for obstructive sleep apnea syndrome (OSAS; defined as an apnea-hypopnea index (AHI) of >15/h of sleep during a polysomnographic recording) were followed for a median period of 887 days. The main outcome measure was the risk ratio for elderly patients associated with nCPAP compliance.Results: Four patients, who remained under treatment, died before the end of the study, and 50 patients stopped their nCPAP therapy for reasons other than death (insomnia, equipment too noisy, etc.). When compliance curves were compared by univariate analysis (log-rank test), the oldest group (57/163 patients, >60 years old) was significantly less compliant with nCPAP than the youngest (P=0.01). However, in the Cox's proportional hazards model, age did not exert any independent effect on compliance with nCPAP after controlling for confounding factors (adjusted relative risk, 1.09, 0.5-2; P=0.70). On the other hand, female sex (adjusted relative risk, 2.8, 1.4-5.4; P=0.002), a body mass index (BMI) of /=12 cmH(2)O (adjusted relative risk, 2.3, 1.2-4.4; P=0.011) were predictive factors for non-compliance.Conclusion: This study suggests that there is no independent effect of age on compliance with nCPAP therapy.

Adult Body Height Is a Good Predictor of Different Dimensions of Cognitive Function in Aged Individuals: A Cross-Sectional Study.

PubMed

Pereira, Vitor H; Costa, Patrício S; Santos, Nadine C; Cunha, Pedro G; Correia-Neves, Margarida; Palha, Joana A; Sousa, Nuno

2016-01-01

Background: Adult height, weight, and adiposity measures have been suggested by some studies to be predictors of depression, cognitive impairment, and dementia. However, the presence of confounding factors and the lack of a thorough neuropsychological evaluation in many of these studies have precluded a definitive conclusion about the influence of anthropometric measures in cognition and depression. In this study we aimed to assess the value of height, weight, and abdominal perimeter to predict cognitive impairment and depressive symptoms in aged individuals. Methods and Findings: Cross-sectional study performed between 2010 and 2012 in the Portuguese general community. A total of 1050 participants were included in the study and randomly selected from local area health authority registries. The cohort was representative of the general Portuguese population with respect to age (above 50 years of age) and gender. Cognitive function was assessed using a battery of tests grouped in two dimensions: general executive function and memory. Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood before and after correction for possible confounding factors (gender, age, school years, physical activity, alcohol consumption, and smoking habits). We found single associations of weight, height, body mass index, abdominal perimeter, and age with executive function, memory and depressive symptoms. However, when included in a predictive model adjusted for gender, age, school years, and lifestyle factors only height prevailed as a significant predictor of general executive function (β = 0.139; p < 0.001) and memory (β = 0.099; p < 0.05). No relation was found between mood and any of the anthropometric measures studied. Conclusions and Relevance: Height is an independent predictor of cognitive function in late-life and its effects on the general and executive function and memory are independent of age, weight, education level, gender, and lifestyle factors. Altogether, our data suggests that modulators of adult height during childhood may irreversibly contribute to cognitive function in adult life and that height should be used in models to predict cognitive performance.

Is there a link between motor vehicle collisions and being a cigarette smoker in Canada? Analysis of survey data from Ontario from 2002 to 2014.

PubMed

Vingilis, Evelyn; Pederson, Linda L; Seeley, Jane; Ialomiteanu, Anca R; Wickens, Christine M; Ferrence, Roberta; Mann, Robert E

2018-05-19

Although most research on drugs and driving has focused on the use of alcohol and cannabis, research that has been conducted on cigarette smoking and collisions has found that smokers have an increased collision involvement. Studies dating from 1967 through 2013 have shown a crude relative risk of about 1.5 among smokers compared to nonsmokers. In Canada, the association between smoking and collisions has not been recently investigated. Studies that have examined the association between smoking and collisions often did not control for all confounding factors, such as alcohol use and driving exposure, which have been associated with increased collision rates. Additionally, a number of these studies were examined in countries and at times when prevalence of smoking was much higher than is currently the case in Canada. The purpose of this research is to examine the association between self-reported current smoking and past-year collision involvement, controlling for confounding factors, in a large representative sample of adult drivers in Ontario, Canada, from 2002 and 2014. Data are based on the Centre for Addiction and Mental Health (CAMH) Monitor, an ongoing, rolling telephone survey of Ontario adults that provides epidemiological surveillance of indicators related to alcohol, tobacco, and other drug use, as well as physical and mental health. The survey uses random-digit-dialing methods via Computer-Assisted Telephone Interview, with response rates over 50%. Prevalence of self-reported collision involvement within the past year for 2002-2014 was 8.6% among those who currently smoke compared to 6.5% of nonsmokers. Logistic regression analysis, controlling for the potential confounding effects of sociodemographics, driving exposure measures, drinking frequency, and hazardous alcohol use, found that the overall odds for collision involvement in the preceding year among current smokers for 2002-2014 was 1.27 (95% confidence interval [CI], 1.06-1.53) times that of nonsmokers. These findings indicate that despite a substantial reduction in overall prevalence of smoking in Canada, smokers still have a significantly increased odds of collision involvement, even when controlling for alcohol and exposure. Additionally, the results are consistent with the increased odds/risks of motor vehicle collisions found in other countries.

Propensity Score-Based Methods versus MTE-Based Methods in Causal Inference: Identification, Estimation, and Application

ERIC Educational Resources Information Center

Zhou, Xiang; Xie, Yu

2016-01-01

Since the seminal introduction of the propensity score (PS) by Rosenbaum and Rubin, PS-based methods have been widely used for drawing causal inferences in the behavioral and social sciences. However, the PS approach depends on the ignorability assumption: there are no unobserved confounders once observed covariates are taken into account. For…

An appraisal of statistical procedures used in derivation of reference intervals.

PubMed

Ichihara, Kiyoshi; Boyd, James C

2010-11-01

When conducting studies to derive reference intervals (RIs), various statistical procedures are commonly applied at each step, from the planning stages to final computation of RIs. Determination of the necessary sample size is an important consideration, and evaluation of at least 400 individuals in each subgroup has been recommended to establish reliable common RIs in multicenter studies. Multiple regression analysis allows identification of the most important factors contributing to variation in test results, while accounting for possible confounding relationships among these factors. Of the various approaches proposed for judging the necessity of partitioning reference values, nested analysis of variance (ANOVA) is the likely method of choice owing to its ability to handle multiple groups and being able to adjust for multiple factors. Box-Cox power transformation often has been used to transform data to a Gaussian distribution for parametric computation of RIs. However, this transformation occasionally fails. Therefore, the non-parametric method based on determination of the 2.5 and 97.5 percentiles following sorting of the data, has been recommended for general use. The performance of the Box-Cox transformation can be improved by introducing an additional parameter representing the origin of transformation. In simulations, the confidence intervals (CIs) of reference limits (RLs) calculated by the parametric method were narrower than those calculated by the non-parametric approach. However, the margin of difference was rather small owing to additional variability in parametrically-determined RLs introduced by estimation of parameters for the Box-Cox transformation. The parametric calculation method may have an advantage over the non-parametric method in allowing identification and exclusion of extreme values during RI computation.

Hurricane exposure and county fetal death rates, utilization of a county environmental quality index for confounding control.

EPA Science Inventory

The effects of natural disasters on public health are a rising concern, with increasing severity of disaster events. Many disaster studies utilize county-level analysis, however most do not control for county level environmental factors. Hurricane exposure during pregnancy could ...

XENOBIOTIC METABOLISM RESEARCH AND ITS APPLICATION TO HUMAN AND ECOLOGICAL EXPOSURE AND RISK ASSESSMENT

EPA Science Inventory

A major uncertainty in risk assessment is determining the exposure of a target organism to a chemical stressor, and a confounding factor is the transformation of the chemical to a toxic metabolite inside the target organism. Physiologically-based pharmacokinetic (PBPK) models are...

ISSUES AND RECCOMMENDATIONS FOR POREWATER TOXCITY TESTING: METHODOLOGICAL UNCERTAINTIES, CONFOUNDING FACTORS AND TOXCITY IDENTIFICATION EVALUATION PROCEDURES

EPA Science Inventory

During the last decade porewater toxicity tests have gained popularity among researchers and managers as tools for the assessment of the presence and biological effects of bioavailable contaminants in aquatic sediments. However, there are a number of information gaps in our know...

Age of Acquisition and Imageability: A Cross-Task Comparison

ERIC Educational Resources Information Center

Ploetz, Danielle M.; Yates, Mark

2016-01-01

Previous research has reported an imageability effect on visual word recognition. Words that are high in imageability are recognised more rapidly than are those lower in imageability. However, later researchers argued that imageability was confounded with age of acquisition. In the current research, these two factors were manipulated in a…

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)

EFFECT OF ARSENICALS ON ULTRAVIOLET-RADIATION-INDUCED GROWTH ARREST AND RELATED SIGNALING EVENTS IN HUMAN KERATINOCYTES

EPA Science Inventory

The molecular mechanisms mediating arsenic-induced carcinogenesis are not well understood. The role of confounding factors such as ultraviolet radiation (UV), add another level of complexity to the study of arsenic carcinogenesis and the cancer risk assessment to humans. We hypot...

Problems in Psychiatric Genetic Research: A Reply to Faraone and Biederman.

ERIC Educational Resources Information Center

Joseph, Jay

2000-01-01

Answers the most important criticisms by Faraone and Biederman in their critique of Joseph's analysis of evidence supporting a genetic basis of attention deficit hyperactivity disorder. Argues that possible genetic and environmental influences in ADHD twin studies are confounded, obscuring inferences about genetic factors. (JPB)

Measuring Systematic Long-Term Trajectories of School Effectiveness Improvement

ERIC Educational Resources Information Center

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

2016-01-01

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

Incidence and Predicted Risk Factors of Pressure Ulcers in Surgical Patients: Experience at a Medical Center in Taipei, Taiwan

PubMed Central

Fu Shaw, Ling; Chang, Pao-Chu; Lee, Jung-Fen; Kung, Huei-Yu

2014-01-01

Purpose. To explore the context of incidence of and associated risk factors for pressure ulcers amongst the population of surgical patients. Methods. The initial study cohort was conducted with a total of 297 patients admitted to a teaching hospital for a surgical operation from November 14th to 27th 2006 in Taipei, Taiwan. The Braden scale, pressure ulcers record sheet, and perioperative patient outcomes free from signs and symptoms of injury related to positioning and related nursing interventions and activities were collected. Results. The incidence of immediate and thirty-minute-later pressure ulcers is 9.8% (29/297) and 5.1% (15/297), respectively. Using logistic regression model, the statistically significantly associated risk factors related to immediate and thirty-minute-later pressure ulcers include operation age, type of anesthesia, type of operation position, type of surgery, admission Braden score, and number of nursing intervention after adjustment for confounding factors. Conclusion. Admission Braden score and number of nursing intervention are well-established protected factors for the development of pressure ulcers. Our study shows that older operation age, type of anesthesia, type of operation position, and type of surgery are also associated with the development of pressure ulcers. PMID:25057484

Associations between Distal Upper Extremity Job Physical Factors and Psychosocial Measures in a Pooled Study

PubMed Central

2015-01-01

Introduction. There is an increasing body of literature relating musculoskeletal diseases to both job physical exposures and psychosocial outcomes. Relationships between job physical exposure measures and psychosocial factors have not been well examined or quantified. These exploratory analyses evaluate relationships between quantified exposures and psychosocial outcomes. Methods. Individualized quantification of duration, repetition, and force and composite scores of the Strain Index (SI) and the Threshold Limit Value for Hand Activity Level (TLV for HAL) were compared to 10 psychosocial measures. Relationships and predicted probabilities were assessed using ordered logistic regression. Analyses were adjusted for age, BMI, and gender. Results and Discussion. Among 1834 study participants there were multiple statistically significant relationships. In general, as duration, repetition, and force increased, psychosocial factors worsened. However, general health and mental exhaustion improved with increasing job exposures. Depression was most strongly associated with increased repetition, while physical exhaustion was most strongly associated with increased force. SI and TLV for HAL were significantly related to multiple psychosocial factors. These relationships persisted after adjustment for strong confounders. Conclusion. This study quantified multiple associations between job physical exposures and occupational and nonoccupational psychosocial factors. Further research is needed to quantify the impacts on occupational health outcomes. PMID:26557686

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.

Association of Personality Traits with Elder Self-Neglect in a Community Dwelling Population

PubMed Central

Dong, XinQi; Simon, Melissa; Wilson, Robert; Beck, Todd; McKinell, Kelly; Evans, Denis

2010-01-01

Objective Elder self-neglect is an important public health issue. However, little is known about the association between personality traits and risk of elder self-neglect among community-dwelling populations. The objectives of this study are: 1) to examine the association of personality traits with elder self-neglect and 2) to examine the association of personality traits with elder self-neglect severity. Methods Population-based study conducted from 1993–2005 of community-dwelling older adults (N=9,056) participating in the Chicago Health Aging Project (CHAP). Subsets of the CHAP participants (N=1,820) were identified for suspected self-neglect by social services agency, which assessed the severity. Personality traits assessed included neuroticism, extraversion, rigidity and information processing. Logistic and linear regressions were used to assess these associations. Results In the bivariate analyses, personality traits (neuroticism, extraversion, information processing, and rigidity) were significantly associated with increased risk of elder self-neglect. However, after adjusting for potential confounders, the above associations were no longer statistically significant. In addition, personality traits were not associated with increased risk of greater self-neglect severity. Furthermore, interaction term analyses of personality traits with health and psychosocial factors were not statistically significant with elder self-neglect outcomes. Conclusion Neuroticism, extraversion, rigidity and information processing were not associated with significantly increased risk of elder self-neglect after consideration of potential confounders. PMID:21788924

Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES

PubMed Central

Lankester, Joanna; Patel, Chirag; Cullen, Mark R.; Ley, Catherine; Parsonnet, Julie

2013-01-01

Background Triclosan—a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies—has the potential to alter both gut microbiota and endocrine function and thereby affect body weight. Methods We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003–2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures—either presence vs. absence or quartiles of triclosan—we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations. Results Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified. Conclusions Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action. PMID:24278238

Eliminating the blood-flow confounding effect in intravoxel incoherent motion (IVIM) using the non-negative least square analysis in liver.

PubMed

Gambarota, Giulio; Hitti, Eric; Leporq, Benjamin; Saint-Jalmes, Hervé; Beuf, Olivier

2017-01-01

Tissue perfusion measurements using intravoxel incoherent motion (IVIM) diffusion-MRI are of interest for investigations of liver pathologies. A confounding factor in the perfusion quantification is the partial volume between liver tissue and large blood vessels. The aim of this study was to assess and correct for this partial volume effect in the estimation of the perfusion fraction. MRI experiments were performed at 3 Tesla with a diffusion-MRI sequence at 12 b-values. Diffusion signal decays in liver were analyzed using the non-negative least square (NNLS) method and the biexponential fitting approach. In some voxels, the NNLS analysis yielded a very fast-decaying component that was assigned to partial volume with the blood flowing in large vessels. Partial volume correction was performed by biexponential curve fitting, where the first data point (b = 0 s/mm 2 ) was eliminated in voxels with a very fast-decaying component. Biexponential fitting with partial volume correction yielded parametric maps with perfusion fraction values smaller than biexponential fitting without partial volume correction. The results of the current study indicate that the NNLS analysis in combination with biexponential curve fitting allows to correct for partial volume effects originating from blood flow in IVIM perfusion fraction measurements. Magn Reson Med 77:310-317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Challenges for the functional diffusion map in pediatric brain tumors

PubMed Central

Grech-Sollars, Matthew; Saunders, Dawn E.; Phipps, Kim P.; Kaur, Ramneek; Paine, Simon M.L.; Jacques, Thomas S.; Clayden, Jonathan D.; Clark, Chris A.

2014-01-01

Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size. PMID:24305721

Dynamic changes in quality of life after three first-line therapies for EGFR mutation-positive advanced non-small-cell lung cancer.

PubMed

Yang, Szu-Chun; Lin, Chien-Chung; Lai, Wu-Wei; Chang, Sheng-Mao; Hwang, Jing-Shiang; Su, Wu-Chou; Wang, Jung-Der

2018-01-01

Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders. From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires. QoL functions after initiation of treatment were estimated using a kernel-smoothing method. Dynamic changes in major determinants were repeatedly assessed for constructing mixed models. A total of 344 patients were enrolled, with 934 repeated assessments. After controlling for performance status, disease progression, EGFR mutation subtype and other confounders, the mixed models showed significantly lower QoL scores for afatinib versus gefitinib in the physical, psychological and social domains, and 10 facets. The differences seemed to appear 10 months after initiation of treatment. In contrast, there was no significant difference between erlotinib and gefitinib in the scores of all domains and facets. QoL in patients receiving afatinib seemed to be lower than in those receiving gefitinib. Since the sample sizes in this study were relatively small, more studies are warranted to corroborate these results.

Dietary approaches to stop hypertension diet and obesity: A cross-sectional study of Iranian children and adolescents.

PubMed

Golpour-Hamedani, Sahar; Mohammadifard, Noushin; Khosravi, Alireza; Feizi, Awat; Safavi, Sayyed Morteza

2017-01-01

Few studies have investigated the effects of dietary approaches to stop hypertension (DASH) diet on obesity in children. The present study was conducted to examine adherence to the DASH diet in relation to obesity in children and adolescents, Isfahan, Iran. A cross-sectional study was carried out among 456 children aged 11-18 years who were selected by random cluster sampling method. Dietary intakes were assessed using a validated Food Frequency Questionnaire (FFQ). The DASH score was constructed based on food items emphasized or minimized in the DASH diet. Anthropometric measurements were conducted based on standard protocols. General and abdominal obesity were defined based on body mass index ≥ 95th percentiles and waist: height ratio of more than 0.5, respectively. Higher adherence to DASH diet was inversely associated with general obesity (odds ratioT1 vs. T3 3.34, 95% confidence interval 1.28-8.75); however, after controlling for confounding factors, this association disappeared. Furthermore, higher adherence to DASH diet was negatively associated with central obesity in children, but the relation was not statistically significant. We concluded that there was an inverse nonsignificant association between adherence to DASH diet and general obesity indices after adjustment for potential confounders. Further, well-designed randomized clinical trial studies are suggested to find out the effect of DASH diet on obesity obviously.

Psychosocial factors at work and self reported health: comparative results of cross sectional and prospective analyses of the French GAZEL cohort

PubMed Central

Niedhammer, I; Chea, M

2003-01-01

Background: Psychosocial factors at work have been found to be significant contributors to health, especially cardiovascular health. Aims: To explore the relation between psychosocial factors at work and self reported health, using cross sectional and prospective analyses for a large occupational cohort of men and women. Methods: Psychosocial factors at work were evaluated using the Karasek questionnaire, designed to measure psychological demands, decision latitude, social support, and physical demands. Self reported health was used as health outcome. Covariates included chronic diseases, and sociodemographic, occupational, and behavioural factors. The cross sectional and prospective analyses concerned respectively 11 447 and 7664 workers. Men and women were analysed separately. Results: Cross sectional analysis revealed significant associations between psychological demands, decision latitude, social support, and physical demands, and self reported health for both men and women. Prospective analysis showed that high psychological demands for both genders, low decision authority for men, and low social support and high physical demands for women were predictive of poor self reported health. These results were independent of potential confounding variables. Conclusions: Results highlight the predictive effects of psychosocial factors at work on self reported health in a one year follow up study. They also underline the need for longitudinal study design and separate analyses for men and women in the field of psychosocial factors at work. PMID:12819285

Evaluation of Alternative Difference-in-Differences Methods

ERIC Educational Resources Information Center

Yu, Bing

2013-01-01

Difference-in-differences (DID) strategies are particularly useful for evaluating policy effects in natural experiments in which, for example, a policy affects some schools and students but not others. However, the standard DID method may produce biased estimation of the policy effect if the confounding effect of concurrent events varies by…

ANOVA with Rasch Measures.

ERIC Educational Resources Information Center

Linacre, John Michael

Various methods of estimating main effects from ordinal data are presented and contrasted. Problems discussed include: (1) at what level to accumulate ordinal data into linear measures; (2) how to maintain scaling across analyses; and (3) the inevitable confounding of within cell variance with measurement error. An example shows three methods of…

Neurocognitive function in an extended Afrikaner-ancestry family with affective illness

PubMed Central

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

Objective To characterize the neuropsychological profile of an extended family with unipolar depression (UPD) and other forms of affective illness. Method We administered a battery of neuropsychological tasks measuring various aspects of executive function and visual and verbal memory to 49 individuals in 1 extended family. Six participants had 1 lifetime episode of major depression (MDE-S), 15 were diagnosed with recurrent major depression (MDE-R), 11 had another DSM-IV diagnosis and 17 subjects were unaffected. Results After controlling for multiple confounding factors, including mood and medication, the MDE-R sample made significantly more errors than unaffected relatives on the Stroop Task, a measure of cognitive control. Conclusion There may be at least 1 subtype of UPD characterized by a state-independent deficit in cognitive control. PMID:17353940

Evaluating disease management program effectiveness: an introduction to time-series analysis.

PubMed

Linden, Ariel; Adams, John L; Roberts, Nancy

2003-01-01

Currently, the most widely used method in the disease management (DM) industry for evaluating program effectiveness is referred to as the "total population approach." This model is a pretest-posttest design, with the most basic limitation being that without a control group, there may be sources of bias and/or competing extraneous confounding factors that offer a plausible rationale explaining the change from baseline. Furthermore, with the current inclination of DM programs to use financial indicators rather than program-specific utilization indicators as the principal measure of program success, additional biases are introduced that may cloud evaluation results. This paper presents a non-technical introduction to time-series analysis (using disease-specific utilization measures) as an alternative, and more appropriate, approach to evaluating DM program effectiveness than the current total population approach.

Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy.

PubMed

Hooijmans, M T; Damon, B M; Froeling, M; Versluis, M J; Burakiewicz, J; Verschuuren, J J G M; Niks, E H; Webb, A G; Kan, H E

2015-11-01

Diffusion tensor imaging (DTI) is a popular method to assess differences in fiber organization in diseased and healthy muscle tissue. Previous work has shown that muscle DTI measurements depend on signal-to-noise ratio (SNR), %fat, and tissue T2. The goal of this study was to evaluate the potential biasing effects of these factors on skeletal muscle DTI data in patients with Duchenne Muscular Dystrophy (DMD). MR images were obtained of the right lower leg of 21 DMD patients and 12 healthy controls on a Philips 3T system. DTI measurements were combined with quantitative in-vivo measures of mean water T2, %fat and SNR to evaluate their effect on DTI parameter estimation. All outcome measures were determined within ROIs drawn for six lower leg muscles. Between group analysis, using all ROIs, revealed a significantly elevated FA in the GCL, SOL and PER muscles (p<0.05) and an increased mean diffusivity (p<0.05) and λ3 (p<0.05) in the TA muscle of DMD patients. In-vivo evaluation of the individual confounders showed behaviour in line with predictions from previous simulation work. To account for these confounders, subsequent analysis used only ROIs with SNR greater than 20. With this criterion we found significantly greater MD in the TA muscle of DMD patient (p<0.009) and λ3 in the TA and GCL muscles (p<0.001) of DMD patients, but no differences in FA. As both increased %fat and lower SNR are expected to reduce the apparent MD and λ3, these between-group differences are likely due to pathophysiology. However, the increased FA, observed when using all ROIs, likely reflects the effect of low SNR and %fat on the DTI parameter estimation. These findings suggest that measuring mean water T2, %fat and SNR is essential to ascribe changes in DTI measures to intrinsic diffusion changes or to confounding influences. Copyright © 2015 John Wiley & Sons, Ltd.

Protective Effect of Hydroxychloroquine on Renal Damage in Patients with Lupus Nephritis: Data from LUMINA, a Multiethnic U.S. Cohort

PubMed Central

Pons-Estel, Guillermo J.; Alarcón, Graciela S.; McGwin, Gerald; Danila, Maria I.; Zhang, Jie; Bastian, Holly M.; Reveille, John D.; Vilá, Luis M.

2010-01-01

Objective To assess if hydroxychloroquine can delay renal damage development in lupus nephritis patients. Methods Lupus nephritis patients (n=256) from LUMINA (n=635), a multiethnic cohort of African Americans, Hispanics and Caucasians, age ≥16 years, disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined per the SLICC Damage Index (≥1 of the following lasting at least six months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria ≥3.5 g and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n=53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potentially confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or World Health Organization (WHO) Class glomerulonephritis were also derived. Results Sixty-three (31.0%) of 203 patients developed renal damage over a mean (standard deviation) disease duration of 5.2 (3.5) years. The most frequent renal damage domain item was proteinuria. Hydroxychloroquine-takers (79.3%) exhibited a lower frequency of WHO Class IV glomerulonephritis, lower disease activity and received lower glucocorticoid doses than non-takers. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (HR=0.12; 95% CI 0.02-0.97; p=0.0464) and reduced (HR=0.29; 95%CI 0.13-0.68; p=0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in hydroxychloroquine non-takers and in WHO Class IV glomerulonephritis (p<0.0001). Conclusions After adjusting for possible confounding factors the protective effect of hydroxychloroquine in retarding renal damage occurrence in SLE is still evident. PMID:19479701

Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: a population-based cohort study

PubMed Central

Yang, Fen; Chen, Jianping; Miao, Mao-Hua; Yuan, Wei; Li, Lin; Liang, Hong; Ehrenstein, Vera; Li, Jiong

2017-01-01

Objective The present study aimed to examine the association between paternal selective serotonin reuptake inhibitor (SSRI) use before conception and the risk of autism spectrum disorder (ASD) in offspring. Design A population-based cohort study. Methods We conducted a cohort study of 669 922 children born from 1998 to 2008, with follow-up throughout 2013. Based on Danish national registers, we linked information on paternal use of SSRIs, ASD diagnosed in children and a range of potential confounders. The children whose fathers used SSRIs during the last 3 months prior to conception were identified as the exposed. Cox regression model was used to estimate the HR for ASD in children. Results Compared with unexposed children, the exposed had a 1.62-fold higher risk of ASD (95% CI 1.33 to 1.96) and the risk attenuated after adjusting for potential confounders, especially fathers’ psychiatric conditions (HR=1.43, 95% CI 1.18 to 1.74). When extending the exposure window to 1 year before conception, the increased risk persisted in children of fathers using SSRIs only from the last year until the last 3 months prior to conception (HR=1.54, 95% CI 1.21 to 1.94) but not in children of fathers using SSRIs only during the last 3 months prior to conception (HR=1.17, 95% CI 0.75 to 1.82). We also performed stratified analyses according to paternal history of affective disorders and observed no increased ASD risk among children whose father had affective disorders. Besides, the sibling analysis showed that the ASD risk did not increase among exposed children compared with their unexposed siblings. Conclusions The mildly increased risk of ASD in the offspring associated with paternal SSRI use before conception may be attributable to paternal underlying psychiatric indications related to SSRI use or other unmeasured confounding factors. PMID:29275337

[Effectiveness of integrated early childhood development intervention on nurturing care for children aged 0-35 months in rural China].

PubMed

Shi, H F; Zhang, J X; Wang, X L; Xu, Y Y; Dong, S L; Zhao, C X; Huang, X N; Zhao, Q; Chen, X F; Zhou, Y; O'Sullivan, Margo; Pouwels, Ron; Scherpbier, Robert W

2018-02-02

Objective: To explore whether Integrated Early Childhood Development (IECD) program has effectively improved the nurturing care for children aged 0-35 months in rural China. Methods: IECD has been implemented by the government of China with support from the United Nations Children's Fund (UNICEF) in four poverty-stricken rural counties since 2014. The interventions targeting the five key components of nurturing care (i.e. child and caregiver health, child nutrition, early learning support, child protection and social security) were delivered through the IECD program to children aged 0 to 35 months and their caregivers. A population-based intervention trial was designed to evaluate intervention effectiveness with data collected in 2013 (baseline) and 2016 (mid-term). The changes of nurturing care in the intervention and control group were analyzed by using a difference-in-differences (DID) model. This approach provided adjustment for sociodemographic and other confounding factors. Results: The baseline and mid-term survey enrolled 1 468 and 1 384 children in the intervention group, and 1 485 and 1 361 in the control group. After two years of implementation, the prevalence of caregiver's depression in the intervention group showed a decrease of 9.1% (mid-term 34.8% (479/1 377) vs. baseline 43.9% (621/1 414)), whereas that in control group showed a decrease of 1.6% (mid-term 34.3% (464/1 353) vs. baseline 35.9% (509/1 419)). With the confounding adjusted in the difference-in-differences model, the decrease of the caregiver's depression prevalence in the intervention group was 7.0% greater than that in the control group ( P= 0.008). The qualified rate of minimum meal frequency in the intervention group showed an increase of 10.4% (mid-term 69.0% (532/771) vs. baseline 58.6% (481/821)), whereas the qualified rate in the intervention group showed an increase of 2.9% (mid-term 66.4% (469/706) vs. baseline 63.5% (508/800)). With the confounding adjusted in the difference-in-differences model, the increase of the qualified rate in the intervention group was 8.2% greater than that in the control group ( P= 0.021). The proportion of violent discipline by caregivers in the intervention group showed a decrease of 6.2% (mid-term 49.1% (478/973) vs. baseline 55.3% (554/1 001)), whereas the proportion in control group showed an increase of 4.5% (mid-term 58.4% (560/959) vs. baseline 53.9% (558/1 036)), and with the confounding adjusted in the difference-in-differences model, the difference in increase rate between two groups was 11.0% ( P= 0.001). The proportion of families with three or more children's books in the intervention group showed an increase of 12.7% (mid-term 42.7% (588/1 378) vs. baseline 30.0% (432/1 440)), whereas the proportion of the control group showed an increase of 4.2% (mid-term 25.7% (349/1 357) vs. baseline 21.5% (298/1 388)), and with the confounding adjusted in the difference-in-differences model, the difference in increase rate between two groups was 6.1% ( P= 0.007). Conclusions: The IECD intervention strategy implemented in rural China effectively improved the mental health of caregivers, optimizes families' child feeding and early stimulation behaviors, while reducing violent discipline and other risk factors. IECD provides better nurturing care for the early development of children aged 0-35 months in rural China.

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

PubMed

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

2015-08-01

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

A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study.

PubMed

Gran, Jon Michael; Røysland, Kjetil; Wolbers, Marcel; Didelez, Vanessa; Sterne, Jonathan A C; Ledergerber, Bruno; Furrer, Hansjakob; von Wyl, Viktor; Aalen, Odd O

2010-11-20

When estimating the effect of treatment on HIV using data from observational studies, standard methods may produce biased estimates due to the presence of time-dependent confounders. Such confounding can be present when a covariate, affected by past exposure, is both a predictor of the future exposure and the outcome. One example is the CD4 cell count, being a marker for disease progression for HIV patients, but also a marker for treatment initiation and influenced by treatment. Fitting a marginal structural model (MSM) using inverse probability weights is one way to give appropriate adjustment for this type of confounding. In this paper we study a simple and intuitive approach to estimate similar treatment effects, using observational data to mimic several randomized controlled trials. Each 'trial' is constructed based on individuals starting treatment in a certain time interval. An overall effect estimate for all such trials is found using composite likelihood inference. The method offers an alternative to the use of inverse probability of treatment weights, which is unstable in certain situations. The estimated parameter is not identical to the one of an MSM, it is conditioned on covariate values at the start of each mimicked trial. This allows the study of questions that are not that easily addressed fitting an MSM. The analysis can be performed as a stratified weighted Cox analysis on the joint data set of all the constructed trials, where each trial is one stratum. The model is applied to data from the Swiss HIV cohort study. Copyright © 2010 John Wiley & Sons, Ltd.

Using expert opinion to quantify unmeasured confounding bias parameters.

PubMed

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

2016-06-27

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

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.

Cytokines as Mediators of Chemotherapy-Associated Cognitive Changes: Current Evidence, Limitations and Directions for Future Research

PubMed Central

Cheung, Yin Ting; Lim, Si Rong; Ho, Han Kiat; Chan, Alexandre

2013-01-01

Objectives While various clinical and pharmacological determinants for chemotherapy-associated cognitive impairment have been identified, conflicting evidence suggests that cytokines might play an intermediary role. The objective of this systematic review was to evaluate the current evidence pertaining to the associations among chemotherapy, cytokines induction and cognitive impairment in cancer patients. Methods A literature search with PubMed and SciVerse Scopus was conducted in March 2013 to gather relevant articles and abstracts that fulfilled the inclusion and exclusion criteria. This review included studies that had performed objective and/or subjective cognitive assessments and cytokine measurements on defined populations of cancer patients who received chemotherapy. Results High methodological heterogeneity existed among the selected studies which differed in cancer populations, subject characteristics, cognitive endpoints, types of cytokines tested and their measurement methods. Weak to moderate correlations were observed between IL-1β, IL-6, TNF-α levels, and different degrees of cognitive impairment. Different types of chemotherapy treatments might lead to varying presentations and severities of cytokine-induced cognitive impairment. Notably, the time concordance between the onset of cytokine induction and occurrence of cognitive impairment was not well elucidated. A number of confounding factors was identified to interfere with the expression levels of cytokines; these confounders included subjects' cancer types, ages, genders, genetics and psychosocial characteristics such as anxiety, depression and fatigue. Conclusion Although existing studies observed cognitive impairment and cytokine dysregulation in patients who receive chemotherapy, our results suggest that the intermediary role of cytokines in post-chemotherapy cognitive impairment is still controversial and requires further evaluation. A list of methodological recommendations is proposed to harmonize future studies of this subject matter. PMID:24339912

Are pregnancy intentions associated with transitions into and out of marriage?

PubMed Central

Maddow-Zimet, Isaac; Lindberg, Laura; Kost, Kathryn; Lincoln, Alicia

2015-01-01

CONTEXT Beyond associations with health outcomes, pregnancy intentions may be associated with social outcomes, including marital transitions. METHODS Linked data from the 2004-2008 Oklahoma Pregnancy Risk Assessment Monitoring System (PRAMS) survey and The Oklahoma Toddler Survey (TOTS) from 2006-2010 were used to examine a four category measure of women’s pregnancy intentions (intended, mistimed <2 years, mistimed >=2 years, unwanted) and changes in marital status between conception, birth and age two. Analyses were stratified by marital status at conception (married, N=3,617; unmarried, N=2,123). Propensity score methods were used to adjust for confounding factors, and logistic regressions were used to estimate the association between pregnancy intention and marital formation and dissolution at birth and child’s age two. RESULTS Intention status was associated with mothers’ marital transitions by child’s age two, both in analyses unadjusted and adjusted for confounding background characteristics. In adjusted models, among women married at conception, those with a birth resulting from an unwanted pregnancy were more likely (OR=2.2) than those with an intended pregnancy to transition out of marriage by the time their child was age two. Among women unmarried at conception, those with an unwanted pregnancy were less likely (OR=.4) than those with an intended pregnancy to marry before the child was age two. Births resulting from mistimed pregnancies were not significantly associated with marital transitions. CONCLUSIONS Women with a child resulting from an unwanted pregnancy are less likely to marry, and less likely to stay married, than women with an intended birth. Future assessments of the consequences of unintended childbearing should distinguish between mistimed and unwanted births. PMID:26929138

Prevalence and associated factors for temporomandibular disorders in Chinese civilian pilots.

PubMed

Yu, Qing; Liu, Yang; Chen, Xi; Chen, Duanjing; Xie, Lu; Hong, Xiao; Wang, Xingyuan; Huang, Haili; Yu, Haiyang

2015-10-01

Piloting is a special profession with prolonged stress, which could induce the occurrence of TMD. This sample is useful to reduce the effect of confounders in the analyses. Based on this, the present study aims to determine the prevalence and associated factors for TMD in civilian pilots of China. A cross-sectional epidemiological survey was carried out in 616 male subjects (aged 23-52 years). The questionnaire included general information, chewing preference (bilateral or unilateral), and Trait Anxiety section of Spielberger State-Trait Anxiety Inventory (STAI-T). The clinical examination contained TMD screening per research diagnostic criteria for TMD and diagnosis of sleep bruxism per American Academy of Sleep Medicine standards. The level of statistical significance was set at P ≤ 0.05. The program was conducted from June 2012 to April 2013, in which period, and the percentage of TMD in the samples we examined was 33.3 % (=205/616). Only high anxiety (OR 2.48; 95 % CI 1.25-4.90) and unilateral chewing preference (OR 12.67; 95 % CI 7.77-20.65) were the most significant associated factors with TMD. Also, salivary cortisol and the STAI-T score had a significant correlation (r = 0.47, P < 0.001). It was more reliable to study the associated factors on TMD with the exclusion of the possible confounding factors, and only unilateral chewing preference and psychological stress had a significant association with TMD. In addition, the salivary cortisol levels might assist to assess psychological stress in epidemiological research.

Self-reported neck pain is associated with migraine but not with tension-type headache in adolescents.

PubMed

Blaschek, Astrid; Decke, Siona; Albers, Lucia; Schroeder, Andreas Sebastian; Lehmann, Steffi; Straube, Andreas; Landgraf, Mirjam N; Heinen, Florian; von Kries, Rüdiger

2014-10-01

The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache. Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body. Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5% and 9.6%. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95% CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95% CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95% CI 0.87-1.69). Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.