Sample records for confounding variables including
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Smith, Eric G.
2015-01-01
Background: Nonrandomized studies typically cannot account for confounding from unmeasured factors. Method: A method is presented that exploits the recently-identified phenomenon of “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors. Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure. Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results: Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met. Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations: Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions: To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is straightforward. The method's routine usefulness, however, has not yet been established, nor has the method been fully validated. Rapid further investigation of this novel method is clearly indicated, given the potential value of its quantitative or qualitative output. PMID:25580226
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Mismeasurement and the resonance of strong confounders: uncorrelated errors.
Marshall, J R; Hastrup, J L
1996-05-15
Greenland first documented (Am J Epidemiol 1980; 112:564-9) that error in the measurement of a confounder could resonate--that it could bias estimates of other study variables, and that the bias could persist even with statistical adjustment for the confounder as measured. An important question is raised by this finding: can such bias be more than trivial within the bounds of realistic data configurations? The authors examine several situations involving dichotomous and continuous data in which a confounder and a null variable are measured with error, and they assess the extent of resultant bias in estimates of the effect of the null variable. They show that, with continuous variables, measurement error amounting to 40% of observed variance in the confounder could cause the observed impact of the null study variable to appear to alter risk by as much as 30%. Similarly, they show, with dichotomous independent variables, that 15% measurement error in the form of misclassification could lead the null study variable to appear to alter risk by as much as 50%. Such bias would result only from strong confounding. Measurement error would obscure the evidence that strong confounding is a likely problem. These results support the need for every epidemiologic inquiry to include evaluations of measurement error in each variable considered.
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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.
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Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.
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.
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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.
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Bias, Confounding, and Interaction: Lions and Tigers, and Bears, Oh My!
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.
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Ananth, Cande V; Schisterman, Enrique F
2017-08-01
Prospective and retrospective cohorts and case-control studies are some of the most important study designs in epidemiology because, under certain assumptions, they can mimic a randomized trial when done well. These assumptions include, but are not limited to, properly accounting for 2 important sources of bias: confounding and selection bias. While not adjusting the causal association for an intermediate variable will yield an unbiased estimate of the exposure-outcome's total causal effect, it is often that obstetricians will want to adjust for an intermediate variable to assess if the intermediate is the underlying driver of the association. Such a practice must be weighed in light of the underlying research question and whether such an adjustment is necessary should be carefully considered. Gestational age is, by far, the most commonly encountered variable in obstetrics that is often mislabeled as a confounder when, in fact, it may be an intermediate. If, indeed, gestational age is an intermediate but if mistakenly labeled as a confounding variable and consequently adjusted in an analysis, the conclusions can be unexpected. The implications of this overadjustment of an intermediate as though it were a confounder can render an otherwise persuasive study downright meaningless. This commentary provides an exposition of confounding bias, collider stratification, and selection biases, with applications in obstetrics and perinatal epidemiology. Copyright © 2017 Elsevier Inc. All rights reserved.
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Bayesian effect estimation accounting for adjustment uncertainty.
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.
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Fatigue and crashes: the case of freight transport in Colombia.
Torregroza-Vargas, Nathaly M; Bocarejo, Juan Pablo; Ramos-Bonilla, Juan P
2014-11-01
Truck drivers have been involved in a significant number of road fatalities in Colombia. To identify variables that could be associated with crashes in which truck drivers are involved, a logistic regression model was constructed. The model had as the response variable a dichotomous variable that included the presence or absence of a crash during a specific trip. As independent variables the model included information regarding a driver's work shift, with variables that could be associated with driver's fatigue. The model also included potential confounders related with road conditions. With the model, it was possible to determine the odds ratio of a crash in relation to several variables, adjusting for confounding. To collect the information about the trips included in the model, a survey among truck drivers was conducted. The results suggest strong associations between crashes (i.e., some of them statistically significant) with the number of stops made during the trip, and the average time of each stop. Survey analysis allowed us to identify the practices that contribute to generating fatigue and unhealthy conditions on the road among professional drivers. A review of national regulations confirmed the lack of legislation on this topic. Copyright © 2014 Elsevier Ltd. All rights reserved.
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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
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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.
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Cannabis use and risk of lung cancer: a case-control study.
Aldington, S; Harwood, M; Cox, B; Weatherall, M; Beckert, L; Hansell, A; Pritchard, A; Robinson, G; Beasley, R
2008-02-01
The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking. A case-control study of lung cancer in adults
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Controlling for confounding variables in MS-omics protocol: why modularity matters.
Smith, Rob; Ventura, Dan; Prince, John T
2014-09-01
As the field of bioinformatics research continues to grow, more and more novel techniques are proposed to meet new challenges and improvements upon solutions to long-standing problems. These include data processing techniques and wet lab protocol techniques. Although the literature is consistently thorough in experimental detail and variable-controlling rigor for wet lab protocol techniques, bioinformatics techniques tend to be less described and less controlled. As the validation or rejection of hypotheses rests on the experiment's ability to isolate and measure a variable of interest, we urge the importance of reducing confounding variables in bioinformatics techniques during mass spectrometry experimentation. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
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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.
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Instrumental variables as bias amplifiers with general outcome and confounding.
Ding, P; VanderWeele, T J; Robins, J M
2017-06-01
Drawing causal inference with observational studies is the central pillar of many disciplines. One sufficient condition for identifying the causal effect is that the treatment-outcome relationship is unconfounded conditional on the observed covariates. It is often believed that the more covariates we condition on, the more plausible this unconfoundedness assumption is. This belief has had a huge impact on practical causal inference, suggesting that we should adjust for all pretreatment covariates. However, when there is unmeasured confounding between the treatment and outcome, estimators adjusting for some pretreatment covariate might have greater bias than estimators without adjusting for this covariate. This kind of covariate is called a bias amplifier, and includes instrumental variables that are independent of the confounder, and affect the outcome only through the treatment. Previously, theoretical results for this phenomenon have been established only for linear models. We fill in this gap in the literature by providing a general theory, showing that this phenomenon happens under a wide class of models satisfying certain monotonicity assumptions. We further show that when the treatment follows an additive or multiplicative model conditional on the instrumental variable and the confounder, these monotonicity assumptions can be interpreted as the signs of the arrows of the causal diagrams.
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Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny
2016-05-01
Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus + + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / + + according to the most widely used HRQOL scores and the effects of increasing grade level on odds for worse ODI scores remained significant after adjusting for potential confounders. However, effects of age group and aetiology should not be neglected. 3.
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ERIC Educational Resources Information Center
Hevel, Michael S.; Weeden, Dustin D.; Pasquesi, Kira; Pascarella, Ernest T.
2015-01-01
We use a longitudinal dataset to explore the effect of fraternity/sorority membership on political orientation and social/political activism. After controlling for a variety of potentially confounding variables, including pretests on the dependent variables, fraternity and sorority members were significantly less liberal that their unaffiliated…
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Mismeasurement and the resonance of strong confounders: correlated errors.
Marshall, J R; Hastrup, J L; Ross, J S
1999-07-01
Confounding in epidemiology, and the limits of standard methods of control for an imperfectly measured confounder, have been understood for some time. However, most treatments of this problem are based on the assumption that errors of measurement in confounding and confounded variables are independent. This paper considers the situation in which a strong risk factor (confounder) and an inconsequential but suspected risk factor (confounded) are each measured with errors that are correlated; the situation appears especially likely to occur in the field of nutritional epidemiology. Error correlation appears to add little to measurement error as a source of bias in estimating the impact of a strong risk factor: it can add to, diminish, or reverse the bias induced by measurement error in estimating the impact of the inconsequential risk factor. Correlation of measurement errors can add to the difficulty involved in evaluating structures in which confounding and measurement error are present. In its presence, observed correlations among risk factors can be greater than, less than, or even opposite to the true correlations. Interpretation of multivariate epidemiologic structures in which confounding is likely requires evaluation of measurement error structures, including correlations among measurement errors.
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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.
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Xu, Ronghui; Hou, Jue; Chambers, Christina D
2018-06-01
Our work was motivated by small cohort studies on the risk of birth defects in infants born to pregnant women exposed to medications. We controlled for confounding using propensity scores (PS). The extremely rare events setting renders the matching or stratification infeasible. In addition, the PS itself may be formed via different approaches to select confounders from a relatively long list of potential confounders. We carried out simulation experiments to compare different combinations of approaches: IPW or regression adjustment, with 1) including all potential confounders without selection, 2) selection based on univariate association between the candidate variable and the outcome, 3) selection based on change in effects (CIE). The simulation showed that IPW without selection leads to extremely large variances in the estimated odds ratio, which help to explain the empirical data analysis results that we had observed. Copyright © 2018 Elsevier Inc. All rights reserved.
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A review of covariate selection for non-experimental comparative effectiveness research.
Sauer, Brian C; Brookhart, M Alan; Roy, Jason; VanderWeele, Tyler
2013-11-01
This paper addresses strategies for selecting variables for adjustment in non-experimental comparative effectiveness research and uses causal graphs to illustrate the causal network that relates treatment to outcome. Variables in the causal network take on multiple structural forms. Adjustment for a common cause pathway between treatment and outcome can remove confounding, whereas adjustment for other structural types may increase bias. For this reason, variable selection would ideally be based on an understanding of the causal network; however, the true causal network is rarely known. Therefore, we describe more practical variable selection approaches based on background knowledge when the causal structure is only partially known. These approaches include adjustment for all observed pretreatment variables thought to have some connection to the outcome, all known risk factors for the outcome, and all direct causes of the treatment or the outcome. Empirical approaches, such as forward and backward selection and automatic high-dimensional proxy adjustment, are also discussed. As there is a continuum between knowing and not knowing the causal, structural relations of variables, we recommend addressing variable selection in a practical way that involves a combination of background knowledge and empirical selection and that uses high-dimensional approaches. This empirical approach can be used to select from a set of a priori variables based on the researcher's knowledge to be included in the final analysis or to identify additional variables for consideration. This more limited use of empirically derived variables may reduce confounding while simultaneously reducing the risk of including variables that may increase bias. Copyright © 2013 John Wiley & Sons, Ltd.
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A Review of Covariate Selection for Nonexperimental Comparative Effectiveness Research
Sauer, Brian C.; Brookhart, Alan; Roy, Jason; Vanderweele, Tyler
2014-01-01
This paper addresses strategies for selecting variables for adjustment in non-experimental comparative effectiveness research (CER), and uses causal graphs to illustrate the causal network that relates treatment to outcome. Variables in the causal network take on multiple structural forms. Adjustment for on a common cause pathway between treatment and outcome can remove confounding, while adjustment for other structural types may increase bias. For this reason variable selection would ideally be based on an understanding of the causal network; however, the true causal network is rarely know. Therefore, we describe more practical variable selection approaches based on background knowledge when the causal structure is only partially known. These approaches include adjustment for all observed pretreatment variables thought to have some connection to the outcome, all known risk factors for the outcome, and all direct causes of the treatment or the outcome. Empirical approaches, such as forward and backward selection and automatic high-dimensional proxy adjustment, are also discussed. As there is a continuum between knowing and not knowing the causal, structural relations of variables, we recommend addressing variable selection in a practical way that involves a combination of background knowledge and empirical selection and that uses the high-dimensional approaches. This empirical approach can be used to select from a set of a priori variables based on the researcher’s knowledge to be included in the final analysis or to identify additional variables for consideration. This more limited use of empirically-derived variables may reduce confounding while simultaneously reducing the risk of including variables that may increase bias. PMID:24006330
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O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E
2011-12-01
When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.
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Drug induced liver injury with analysis of alternative causes as confounding variables.
Teschke, Rolf; Danan, Gaby
2018-04-01
Drug-induced liver injury (DILI) is rare compared to the worldwide frequent acute or chronic liver diseases. Therefore, patients included in series of suspected DILI are at high risk of not having DILI, whereby alternative causes may confound the DILI diagnosis. The aim of this review is to evaluate published case series of DILI for alternative causes. Relevant studies were identified using a computerized search of the Medline database for publications from 1993 through 30 October 2017. We used the following terms: drug hepatotoxicity, drug induced liver injury, hepatotoxic drugs combined with diagnosis, causality assessment and alternative causes. Alternative causes as variables confounding the DILI diagnosis emerged in 22 published DILI case series, ranging from 4 to 47%. Among 13 335 cases of suspected DILI, alternative causes were found to be more likely in 4555 patients (34.2%), suggesting that the suspected DILI was probably not DILI. Biliary diseases such as biliary obstruction, cholangitis, choledocholithiasis, primary biliary cholangitis and primary sclerosing cholangitis were among the most missed diagnoses. Alternative causes included hepatitis B, C and E, cytomegalovirus, Epstein-Barr virus, ischemic hepatitis, cardiac hepatopathy, autoimmune hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and alcoholic liver disease. In more than one-third of published global DILI case series, alternative causes as published in these reports confounded the DILI diagnosis. In the future, published DILI case series should include only patients with secured DILI diagnosis, preferentially established by prospective use of scored items provided by robust diagnostic algorithms such as the updated Roussel Uclaf causality assessment method. © 2018 The British Pharmacological Society.
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Fischer, Susanne; Duncko, Roman; Hatch, Stephani L; Papadopoulos, Andrew; Goodwin, Laura; Frissa, Souci; Hotopf, Matthew; Cleare, Anthony J
2017-02-01
Hypothalamic-pituitary-adrenal (HPA) measures are crucial for research into stress and stress-related disorders. Most HPA measures fluctuate depending on diurnal rhythms and state confounders. Hair cortisol concentrations (HCC) are less susceptible to such fluctuations, but less is known about trait-like confounders. Using a community sample, we tested the relationship between HCC and a range of variables including demographic variables, hair treatment, and medication, as well as psychosocial variables, namely childhood trauma, critical life events, and depressive symptoms. Hair samples were collected from 144 individuals from the South East London Community Health (SELCoH) study. Childhood trauma, life events, and depressive symptoms were measured, together with age, sex, ethnicity, relationship status, educational attainment, employment status, occupational social class, hair washing frequency, hair treatments, season reflected in the hair sample, hazardous drinking, smoking, medication intake, and body mass index. Hair samples reflecting the past 3 months were collected and analysed using immunoassays. First, correlations (continuous variables) and simple linear regressions (dichotomous variables) were conducted to identify sociodemographic, hair-related, and lifestyle determinants of HCC. Next, multiple linear regressions were conducted to test the relationship between psychosocial variables and HCC when controlling for the identified confounders. Age (r=-0.17, p=0.050), White British ethnicity (β=-0.19, p=0.023), heat-based treatments (β=-0.22, p=0.010), and winter season (β=-0.18, p=0.024) were associated with lower HCC, whereas summer season (β=0.24, p=0.024), painkillers (β=0.25, p=0.003), anxiolytics/antidepressants (β=0.21, p=0.014), and hormonal contraceptives (β=0.27, p=0.006) were associated with higher HCC. Controlling for these confounders, physical neglect during childhood (β=-0.17, p=0.057), war-related experiences (β=0.20, p=0.027), separation (β=0.18, p=0.054), and being the victim of a serious crime (β=-0.17, p=0.062) were linked with altered HCC. Our findings suggest that variation in HCC occurs according to sociodemographic, hair-related, and lifestyle variables, and that certain associations between stress and altered HCC can only be revealed when accounting for these confounders. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Gender effects in gaming research: a case for regression residuals?
Pfister, Roland
2011-10-01
Numerous recent studies have examined the impact of video gaming on various dependent variables, including the players' affective reactions, positive as well as detrimental cognitive effects, and real-world aggression. These target variables are typically analyzed as a function of game characteristics and player attributes-especially gender. However, findings on the uneven distribution of gaming experience between males and females, on the one hand, and the effect of gaming experience on several target variables, on the other hand, point at a possible confound when gaming experiments are analyzed with a standard analysis of variance. This study uses simulated data to exemplify analysis of regression residuals as a potentially beneficial data analysis strategy for such datasets. As the actual impact of gaming experience on each of the various dependent variables differs, the ultimate benefits of analysis of regression residuals entirely depend on the research question, but it offers a powerful statistical approach to video game research whenever gaming experience is a confounding factor.
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Dale, Caroline; Nüesch, Eveline; Prieto-Merino, David; Choi, Minkyoung; Amuzu, Antoinette; Ebrahim, Shah; Casas, Juan P.; Davey-Smith, George
2015-01-01
Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women’s Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3 – 3.1 versus OR = 1.2; 95% CI 0.7 – 1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding. PMID:25884834
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Tsutsumi, Chiyo; Kakuma, Tatsuyuki
2015-01-01
Associations have been reported between periodontal disease and increased cardiovascular disease risk, as well as between healthy self-reported tooth brushing behavior and reduced cardiovascular disease risk. We examined the association between self-reported tooth brushing behavior and the risk of metabolic syndrome (MetS) using a large medical check-up database. A total of 12,548 medical checkup records from a medical screening center in a city in southwest Japan were assessed. Subjects were aged 30 to 59 years. As lifestyle is associated with both tooth brushing and MetS, many lifestyle variables were considered as potential confounders. Logistic regression model were employed with a list of 127 lifestyle variables. Twenty variables associated with both tooth brushing and MetS were selected for both males and females. Furthermore, final confounding variables were selected by principal component analysis to avoid collinearity problems. The association of tooth brushing and MetS was evaluated for males and females separately by calculating adjusted odds ratios (ORs) with selected confounders plus age. The association between daily tooth brushing frequency and MetS risk for both genders was significant after adjusting for confounders, with the risk of MetS decreasing with increased frequency of daily tooth brushing (adjusted OR = 0.57 (95%Cl:0.48-0.81), 0.50 (95%Cl:0.35-0.71), 0.42 (95%Cl: 0.29-0.61) for males and adjusted OR = 0.65 (95%Cl:0.48-0.87), 0.44 (95%Cl:0.32-0.62) for females). Therefore, oral hygiene, including the frequency of tooth brushing as a significant component, may be an important factor in preventing MetS.
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An introduction to instrumental variables analysis: part 1.
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.
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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.
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Pandis, Nikolaos; Polychronopoulou, Argy; Madianos, Phoebus; Makou, Margarita; Eliades, Theodore
2011-06-01
The objective of this article was to record reporting characteristics related to study quality of research published in major specialty dental journals with the highest impact factor (Journal of Endodontics, Journal of Oral and Maxillofacial Surgery, American Journal of Orthodontics and Dentofacial Orthopedics; Pediatric Dentistry, Journal of Clinical Periodontology, and International Journal of Prosthetic Dentistry). The included articles were classified into the following 3 broad subject categories: (1) cross-sectional (snap-shot), (2) observational, and (3) interventional. Multinomial logistic regression was conducted for effect estimation using the journal as the response and randomization, sample calculation, confounding discussed, multivariate analysis, effect measurement, and confidence intervals as the explanatory variables. The results showed that cross-sectional studies were the dominant design (55%), whereas observational investigations accounted for 13%, and interventions/clinical trials for 32%. Reporting on quality characteristics was low for all variables: random allocation (15%), sample size calculation (7%), confounding issues/possible confounders (38%), effect measurements (16%), and multivariate analysis (21%). Eighty-four percent of the published articles reported a statistically significant main finding and only 13% presented confidence intervals. The Journal of Clinical Periodontology showed the highest probability of including quality characteristics in reporting results among all dental journals. Copyright © 2011 Elsevier Inc. All rights reserved.
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Sinclair, Thomas R; Manandhar, Anju; Shekoofa, Avat; Rosas-Anderson, Pablo; Bagherzadi, Laleh; Schoppach, Remy; Sadok, Walid; Rufty, Thomas W
2017-04-01
Theoretical derivation predicted growth retardation due to pot water limitations, i.e., pot binding. Experimental observations were consistent with these limitations. Combined, these results indicate a need for caution in high-throughput screening and phenotyping. Pot experiments are a mainstay in many plant studies, including the current emphasis on developing high-throughput, phenotyping systems. Pot studies can be vulnerable to decreased physiological activity of the plants particularly when pot volume is small, i.e., "pot binding". It is necessary to understand the conditions under which pot binding may exist to avoid the confounding influence of pot binding in interpreting experimental results. In this paper, a derivation is offered that gives well-defined conditions for the occurrence of pot binding based on restricted water availability. These results showed that not only are pot volume and plant size important variables, but the potting media is critical. Artificial potting mixtures used in many studies, including many high-throughput phenotyping systems, are particularly susceptible to the confounding influences of pot binding. Experimental studies for several crop species are presented that clearly show the existence of thresholds of plant leaf area at which various pot sizes and potting media result in the induction of pot binding even though there may be no immediate, visual plant symptoms. The derivation and experimental results showed that pot binding can readily occur in plant experiments if care is not given to have sufficiently large pots, suitable potting media, and maintenance of pot water status. Clear guidelines are provided for avoiding the confounding effects of water-limited pot binding in studying plant phenotype.
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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…
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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.
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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.
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Tutorial in Biostatistics: Instrumental Variable Methods for Causal Inference*
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
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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
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Landau, Sabine; Emsley, Richard; Dunn, Graham
2018-06-01
Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of the three processes involving baseline measures of intermediate or clinical outcomes is operating. Necessary assumptions for the change score approach (B) to provide unbiased estimates under either process include the independence of baseline measures and change scores of the intermediate variable. Finally, estimates provided by the analysis of covariance approach (C) were found to be unbiased under all the three processes considered here. When applied to the example, there was evidence of mediation under all methods but the estimate of the indirect effect depended on the approach used with the proportion mediated varying from 57% to 86%. Trialists planning mediation analyses should measure baseline values of putative mediators as well as of continuous clinical outcomes. An analysis of covariance approach is recommended to avoid potential biases due to confounding processes involving baseline measures of intermediate or clinical outcomes, and not simply for increased precision.
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Bollen, Kenneth A
2007-06-01
R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. Copyright 2007 APA, all rights reserved.
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NASA Astrophysics Data System (ADS)
Abdussalam, Auwal; Monaghan, Andrew; Dukic, Vanja; Hayden, Mary; Hopson, Thomas; Leckebusch, Gregor
2013-04-01
Northwest Nigeria is a region with high risk of bacterial meningitis. Since the first documented epidemic of meningitis in Nigeria in 1905, the disease has been endemic in the northern part of the country, with epidemics occurring regularly. In this study we examine the influence of climate on the interannual variability of meningitis incidence and epidemics. Monthly aggregate counts of clinically confirmed hospital-reported cases of meningitis were collected in northwest Nigeria for the 22-year period spanning 1990-2011. Several generalized linear statistical models were fit to the monthly meningitis counts, including generalized additive models. Explanatory variables included monthly records of temperatures, humidity, rainfall, wind speed, sunshine and dustiness from weather stations nearest to the hospitals, and a time series of polysaccharide vaccination efficacy. The effects of other confounding factors -- i.e., mainly non-climatic factors for which records were not available -- were estimated as a smooth, monthly-varying function of time in the generalized additive models. Results reveal that the most important explanatory climatic variables are mean maximum monthly temperature, relative humidity and dustiness. Accounting for confounding factors (e.g., social processes) in the generalized additive models explains more of the year-to-year variation of meningococcal disease compared to those generalized linear models that do not account for such factors. Promising results from several models that included only explanatory variables that preceded the meningitis case data by 1-month suggest there may be potential for prediction of meningitis in northwest Nigeria to aid decision makers on this time scale.
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“Skill of Generalized Additive Model to Detect PM2.5 Health ...
Summary. Measures of health outcomes are collinear with meteorology and air quality, making analysis of connections between human health and air quality difficult. The purpose of this analysis was to determine time scales and periods shared by the variables of interest (and by implication scales and periods that are not shared). Hospital admissions, meteorology (temperature and relative humidity), and air quality (PM2.5 and daily maximum ozone) for New York City during the period 2000-2006 were decomposed into temporal scales ranging from 2 days to greater than two years using a complex wavelet transform. Health effects were modeled as functions of the wavelet components of meteorology and air quality using the generalized additive model (GAM) framework. This simulation study showed that GAM is extremely successful at extracting and estimating a health effect embedded in a dataset. It also shows that, if the objective in mind is to estimate the health signal but not to fully explain this signal, a simple GAM model with a single confounder (calendar time) whose smooth representation includes a sufficient number of constraints is as good as a more complex model.Introduction. In the context of wavelet regression, confounding occurs when two or more independent variables interact with the dependent variable at the same frequency. Confounding also acts on a variety of time scales, changing the PM2.5 coefficient (magnitude and sign) and its significance ac
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Pingault, Jean Baptiste; Côté, Sylvana M; Petitclerc, Amélie; Vitaro, Frank; Tremblay, Richard E
2015-01-01
Parental educational expectations have been associated with children's educational attainment in a number of long-term longitudinal studies, but whether this relationship is causal has long been debated. The aims of this prospective study were twofold: 1) test whether low maternal educational expectations contributed to failure to graduate from high school; and 2) compare the results obtained using different strategies for accounting for confounding variables (i.e. multivariate regression and propensity score matching). The study sample included 1,279 participants from the Quebec Longitudinal Study of Kindergarten Children. Maternal educational expectations were assessed when the participants were aged 12 years. High school graduation—measuring educational attainment—was determined through the Quebec Ministry of Education when the participants were aged 22-23 years. Findings show that when using the most common statistical approach (i.e. multivariate regressions to adjust for a restricted set of potential confounders) the contribution of low maternal educational expectations to failure to graduate from high school was statistically significant. However, when using propensity score matching, the contribution of maternal expectations was reduced and remained statistically significant only for males. The results of this study are consistent with the possibility that the contribution of parental expectations to educational attainment is overestimated in the available literature. This may be explained by the use of a restricted range of potential confounding variables as well as the dearth of studies using appropriate statistical techniques and study designs in order to minimize confounding. Each of these techniques and designs, including propensity score matching, has its strengths and limitations: A more comprehensive understanding of the causal role of parental expectations will stem from a convergence of findings from studies using different techniques and designs.
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Grover, Sandeep; Del Greco M, Fabiola; Stein, Catherine M; Ziegler, Andreas
2017-01-01
Confounding and reverse causality have prevented us from drawing meaningful clinical interpretation even in well-powered observational studies. Confounding may be attributed to our inability to randomize the exposure variable in observational studies. Mendelian randomization (MR) is one approach to overcome confounding. It utilizes one or more genetic polymorphisms as a proxy for the exposure variable of interest. Polymorphisms are randomly distributed in a population, they are static throughout an individual's lifetime, and may thus help in inferring directionality in exposure-outcome associations. Genome-wide association studies (GWAS) or meta-analyses of GWAS are characterized by large sample sizes and the availability of many single nucleotide polymorphisms (SNPs), making GWAS-based MR an attractive approach. GWAS-based MR comes with specific challenges, including multiple causality. Despite shortcomings, it still remains one of the most powerful techniques for inferring causality.With MR still an evolving concept with complex statistical challenges, the literature is relatively scarce in terms of providing working examples incorporating real datasets. In this chapter, we provide a step-by-step guide for causal inference based on the principles of MR with a real dataset using both individual and summary data from unrelated individuals. We suggest best possible practices and give recommendations based on the current literature.
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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
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Lynch, Wendy D; Sherman, Bruce W
2014-01-01
When corporate health researchers examine the effects of health on business outcomes or the effect of health interventions on health and business outcomes, results will necessarily be confounded by the corporate environment(s) in which they are studied. In this research setting, most studies control for factors traditionally identified in public health, such as demographics and health status. Nevertheless, often overlooked is the extent to which company policies can also independently impact health care cost, work attendance, and productivity outcomes. With changes in employment and benefits practices resulting from health care reform, including incentives and plan design options, consideration of these largely neglected variables in research design has become increasingly important. This commentary summarizes existing knowledge regarding the implications of policy variations in research outcomes and provides a framework for incorporating them into future employer-based research.
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Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis
Yang, Fan; Wang, Jiebiao; Pierce, Brandon L.; Chen, Lin S.
2017-01-01
The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is “mediation” by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are “cis-mediators” of trans-eQTLs, including those “cis-hubs” involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types. PMID:29021290
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Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S
2017-11-01
The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.
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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.
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Learning at the Speed of Light: Deep Learning and Accelerated Online Graduate Courses
ERIC Educational Resources Information Center
Trekles, Anastasia M.
2013-01-01
An increasing number of university programs, particularly at the graduate level, are moving to an accelerated, time-compressed model for online degree offerings. However, the literature revealed that research in distance education effectiveness is still confounded by many variables, including course design and student approach to learning.…
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Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort
Green, Emma; Shafto, Meredith A.; Matthews, Fiona E.; White, Simon R.
2015-01-01
This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups. PMID:26690191
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Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort.
Green, Emma; Shafto, Meredith A; Matthews, Fiona E; White, Simon R
2015-12-07
This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups.
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Reporting of methodological features in observational studies of pre-harvest food safety.
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.
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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.
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ERIC Educational Resources Information Center
Caroll, Edward
1983-01-01
Reviews a study which found that symptoms associated with posttraumatic stress disorder (PTSD) are neither unique to or common among Vietnam veteran psychiatric patients or their Korean war counterparts. Questions choice of study sample, confounding variables, and source of data. A rebuttal by the original author is included. (WAS)
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Yee, Lydia T S
2017-01-01
Words are frequently used as stimuli in cognitive psychology experiments, for example, in recognition memory studies. In these experiments, it is often desirable to control for the words' psycholinguistic properties because differences in such properties across experimental conditions might introduce undesirable confounds. In order to avoid confounds, studies typically check to see if various affective and lexico-semantic properties are matched across experimental conditions, and so databases that contain values for these properties are needed. While word ratings for these variables exist in English and other European languages, ratings for Chinese words are not comprehensive. In particular, while ratings for single characters exist, ratings for two-character words-which often have different meanings than their constituent characters, are scarce. In this study, ratings for 292 two-character Chinese nouns were obtained from Cantonese speakers in Hong Kong. Affective variables, including valence and arousal, and lexico-semantic variables, including familiarity, concreteness, and imageability, were rated in the study. The words were selected from a film subtitle database containing word frequency information that could be extracted and listed alongside the resulting ratings. Overall, the subjective ratings showed good reliability across all rated dimensions, as well as good reliability within and between the different groups of participants who each rated a subset of the words. Moreover, several well-established relationships between the variables found consistently in other languages were also observed in this study, demonstrating that the ratings are valid. The resulting word database can be used in studies where control for the above psycholinguistic variables is critical to the research design.
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DeMaris, Alfred
2014-01-01
Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904
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Correction of confounding bias in non-randomized studies by appropriate weighting.
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.
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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.
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Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M; Langbehn, Doug R; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J
2016-01-11
Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.
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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.
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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.
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Poppers, Kaposi's sarcoma, and HIV infection: empirical example of a strong confounding effect?
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.
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Pingault, Jean Baptiste; Côté, Sylvana M.; Petitclerc, Amélie; Vitaro, Frank; Tremblay, Richard E.
2015-01-01
Background Parental educational expectations have been associated with children’s educational attainment in a number of long-term longitudinal studies, but whether this relationship is causal has long been debated. The aims of this prospective study were twofold: 1) test whether low maternal educational expectations contributed to failure to graduate from high school; and 2) compare the results obtained using different strategies for accounting for confounding variables (i.e. multivariate regression and propensity score matching). Methodology/Principal Findings The study sample included 1,279 participants from the Quebec Longitudinal Study of Kindergarten Children. Maternal educational expectations were assessed when the participants were aged 12 years. High school graduation – measuring educational attainment – was determined through the Quebec Ministry of Education when the participants were aged 22–23 years. Findings show that when using the most common statistical approach (i.e. multivariate regressions to adjust for a restricted set of potential confounders) the contribution of low maternal educational expectations to failure to graduate from high school was statistically significant. However, when using propensity score matching, the contribution of maternal expectations was reduced and remained statistically significant only for males. Conclusions/Significance The results of this study are consistent with the possibility that the contribution of parental expectations to educational attainment is overestimated in the available literature. This may be explained by the use of a restricted range of potential confounding variables as well as the dearth of studies using appropriate statistical techniques and study designs in order to minimize confounding. Each of these techniques and designs, including propensity score matching, has its strengths and limitations: A more comprehensive understanding of the causal role of parental expectations will stem from a convergence of findings from studies using different techniques and designs. PMID:25803867
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hu, H.; Kim, Rokho; Korrick, S.
1996-12-31
In an earlier report based on participants in the Veterans Administration Normative Aging Study, we found a significant association between the risk of hypertension and lead levels in tibia. To examine the possible confounding effects of education and occupation, we considered in this study five levels of education and three levels of occupation as independent variables in the statistical model. Of 1,171 active subjects seen between August 1991 and December 1994, 563 provided complete data for this analysis. In the initial logistic regression model, acre and body mass index, family history of hypertension, and dietary sodium intake, but neither cumulativemore » smoking nor alcohol ingestion, conferred increased odds ratios for being hypertensive that were statistically significant. When the lead biomarkers were added separately to this initial logistic model, tibia lead and patella lead levels were associated with significantly elevated odds ratios for hypertension. In the final backward elimination logistic regression model that included categorical variables for education and occupation, the only variables retained were body mass index, family history of hypertension, and tibia lead level. We conclude that education and occupation variables were not confounding the association between the lead biomarkers and hypertension that we reported previously. 27 refs., 3 tabs.« less
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The Effects of Age on Second Language Grammar and Speech Production
ERIC Educational Resources Information Center
Huang, Becky H.
2014-01-01
The current study examined the age of learning effect on second language (L2) acquisition. The research goals of the study were twofold: to test whether there is an independent age effect controlling for other potentially confounding variables, and to clarify the age effect across L2 grammar and speech production domains. The study included 118…
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Measuring the wetting angle and perimeter of single wood pulp fibers : a modified method
John H. Klungness
1981-01-01
In pulp processing development it is often necessary to measure the effect of a process variable on individual pulp fiber wettability. Such processes would include drying of market pulps, recycling of secondary fibers, and surface modification of fibers as in sizing. However, if wettability is measured on a fiber sheet surface, the results are confounded by...
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NASA Astrophysics Data System (ADS)
Nelson, N.; Munoz-Carpena, R.; Kaplan, D. A.; Phlips, E. J.
2016-12-01
In many aquatic systems, cyanobacteria form harmful blooms capable of producing toxins, prompting hypoxia, and/or introducing internal nitrogen loads via N2-fixation, among other impacts. Traditionally, system-specific cyanobacteria drivers are determined by performing controlled experiments and bioassays, but these approaches may neglect the influences of confounding factors and over assign importance to only those variables considered within experimental designs. For example, a bioassay may conclude that the cyanobacteria in a particular system are limited by phosphorus, but will not explicitly take into account the role of flow as a control on phosphorus delivery. This study aims to address this analytical gap by identifying environmental controls on cyanobacteria while removing the effects of potentially confounding variables. In the present work, we evaluate a unique long-term (17 year) dataset composed of monthly observations of phytoplankton and zooplankton species abundances, water quality constituents, and hydrologic variables from Lake George, a flow-through lake of the St. Johns River (FL) impacted by cyanobacterial blooms. Using conditional Granger causality analysis, a time series approach that infers causality while removing the effects of confounding variables, data were evaluated to identify biological and physicochemical drivers of cyanobacteria. The analysis was performed for three response variable sets: total cyanobacteria, N2-fixers and non-fixers, and cyanobacteria genera. Results depicted increasing levels of ecological complexity as subdivisions of cyanobacteria became more detailed; whereas causal networks produced from analyses of cyanobacteria genera provided novel insights relevant for management (i.e. nutrients, flow), the total cyanobacteria network only included water temperature as a significant driver. Additionally, the more detailed cyanobacteria subdivisions uncovered that N2-fixation was only evident with the earliest season bloomer, thus indicating that early season bloomers may be facilitating later-season growth. These findings highlight the importance of detailed monitoring efforts, and indicate that greater emphasis needs to be placed on the role of early bloomers in phytoplankton dynamics, as it relates to management efforts.
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Truthmann, Julia; Mensink, Gert B M; Bosy-Westphal, Anja; Hapke, Ulfert; Scheidt-Nave, Christa; Schienkiewitz, Anja
2017-06-10
This study examined sex-specific differences in physical health-related quality of life (HRQoL) across subgroups of metabolic health and obesity. We specifically asked whether (1) obesity is related to lower HRQoL independent of metabolic health status and potential confounders, and (2) whether associations are similar in men and women. We used cross-sectional data from the German Health Interview and Examination Survey 2008-11. Physical HRQoL was measured using the Short Form-36 version 2 physical component summary (PCS) score. Based on harmonized ATPIII criteria for the definition of the metabolic health and a body mass index ≥ 30 kg/m 2 to define obesity, individuals were classified as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Sex-specific analyses including multivariable linear regression analyses were based on PCS as the dependent variable, metabolic health and obesity category as the independent variable with three categories and MHNO as the reference, and age, education, lifestyle and comorbidities as confounders. This study included 6860 participants (3298 men, 3562 women). Compared to MHNO, all other metabolic health and obesity categories had significantly lower PCS in both sexes. As reflected by the beta coefficients [95% confidence interval] from bivariable linear regression models, a significant inverse association with PCS was strongest for MUO (men: -7.0 [-8.2; -5.8]; women: -9.0 [-10.2; -7.9]), intermediate for MUNO (men: -4.2 [-5.3; -3.1]; women: -5.6 [-6.8; -4.4]) and least pronounced for MHO (men: -2.2 [-3.6; -0.8]; women -3.9 [-5.4; -2.5]). Differences in relation to MHNO remained statistically significant for all groups after adjusting for confounders, but decreased in particular for MUNO (men:-1.3 [-2.3; -0.3]; women: -1.5 [-2.7; -0.3]. Obesity was significantly related to lower physical HRQoL, independent of metabolic health status. Potential confounders including age, educational status, health-related behaviors, and comorbidities explained parts of the inverse relationship. Associations were evident in both sexes and consistently more pronounced among women than men.
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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.
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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
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Implementing the undergraduate mini-CEX: a tailored approach at Southampton University.
Hill, Faith; Kendall, Kathleen; Galbraith, Kevin; Crossley, Jim
2009-04-01
The mini-clinical evaluation exercise (mini-CEX) is widely used in the UK to assess clinical competence, but there is little evidence regarding its implementation in the undergraduate setting. This study aimed to estimate the validity and reliability of the undergraduate mini-CEX and discuss the challenges involved in its implementation. A total of 3499 mini-CEX forms were completed. Validity was assessed by estimating associations between mini-CEX score and a number of external variables, examining the internal structure of the instrument, checking competency domain response rates and profiles against expectations, and by qualitative evaluation of stakeholder interviews. Reliability was evaluated by overall reliability coefficient (R), estimation of the standard error of measurement (SEM), and from stakeholders' perceptions. Variance component analysis examined the contribution of relevant factors to students' scores. Validity was threatened by various confounding variables, including: examiner status; case complexity; attachment specialty; patient gender, and case focus. Factor analysis suggested that competency domains reflect a single latent variable. Maximum reliability can be achieved by aggregating scores over 15 encounters (R = 0.73; 95% confidence interval [CI] +/- 0.28 based on a 6-point assessment scale). Examiner stringency contributed 29% of score variation and student attachment aptitude 13%. Stakeholder interviews revealed staff development needs but the majority perceived the mini-CEX as more reliable and valid than the previous long case. The mini-CEX has good overall utility for assessing aspects of the clinical encounter in an undergraduate setting. Strengths include fidelity, wide sampling, perceived validity, and formative observation and feedback. Reliability is limited by variable examiner stringency, and validity by confounding variables, but these should be viewed within the context of overall assessment strategies.
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Dettenborn, L; Tietze, A; Kirschbaum, C; Stalder, T
2012-11-01
To inform the future use of hair cortisol measurement, we have investigated influences of potential confounding variables (natural hair colour, frequency of hair washes, age, sex, oral contraceptive (OC) use and smoking status) on hair cortisol levels. The main study sample comprised 360 participants (172 women) covering a wide range of ages (1-91 years; mean = 25.95). In addition, to more closely examine influences of natural hair colour and young age on hair cortisol levels, two additional samples comprising 69 participants with natural blond or dark brown hair (hair colour sample) as well as 28 young children and 34 adults (young age sample) were recruited. Results revealed a lack of an effect for natural hair colour, OC use, and smoking status on hair cortisol levels (all p's >0.10). No influence of frequency of hair washes was seen for proximal hair segments (p = 0.335) but for the third hair segment indicating lower cortisol content (p = 0.008). We found elevated hair cortisol levels in young children and older adults (p < 0.001). Finally, men showed higher hair cortisol levels than women (p = 0.002). The present data indicate that hair cortisol measurement provides a useful tool in stress-related psychobiological research when applied with the consideration of possible confounders including age and sex.
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Assessing mediation using marginal structural models in the presence of confounding and moderation
Coffman, Donna L.; Zhong, Wei
2012-01-01
This paper presents marginal structural models (MSMs) with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of non-randomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PMID:22905648
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Assessing mediation using marginal structural models in the presence of confounding and moderation.
Coffman, Donna L; Zhong, Wei
2012-12-01
This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of nonrandomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PsycINFO Database Record (c) 2013 APA, all rights reserved.
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Directed acyclic graphs (DAGs): an aid to assess confounding in dental research.
Merchant, Anwar T; Pitiphat, Waranuch
2002-12-01
Confounding, a special type of bias, occurs when an extraneous factor is associated with the exposure and independently affects the outcome. In order to get an unbiased estimate of the exposure-outcome relationship, we need to identify potential confounders, collect information on them, design appropriate studies, and adjust for confounding in data analysis. However, it is not always clear which variables to collect information on and adjust for in the analyses. Inappropriate adjustment for confounding can even introduce bias where none existed. Directed acyclic graphs (DAGs) provide a method to select potential confounders and minimize bias in the design and analysis of epidemiological studies. DAGs have been used extensively in expert systems and robotics. Robins (1987) introduced the application of DAGs in epidemiology to overcome shortcomings of traditional methods to control for confounding, especially as they related to unmeasured confounding. DAGs provide a quick and visual way to assess confounding without making parametric assumptions. We introduce DAGs, starting with definitions and rules for basic manipulation, stressing more on applications than theory. We then demonstrate their application in the control of confounding through examples of observational and cross-sectional epidemiological studies.
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ERIC Educational Resources Information Center
Hevel, Michael S.; Martin, Georgianna L.; Weeden, Dustin D.; Pascarella, Ernest T.
2015-01-01
We use a longitudinal national dataset to explore the direct and conditional effects of fraternity/sorority membership on students' educational outcomes in the 4th year of college. Controlling for a variety of potentially confounding variables, including pretest measures of the outcomes, we find no direct effect of fraternity/sorority membership…
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Sample size calculations for case-control studies
This R package can be used to calculate the required samples size for unconditional multivariate analyses of unmatched case-control studies. The sample sizes are for a scalar exposure effect, such as binary, ordinal or continuous exposures. The sample sizes can also be computed for scalar interaction effects. The analyses account for the effects of potential confounder variables that are also included in the multivariate logistic model.
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Overcoming ecologic bias using the two-phase study design.
Wakefield, Jon; Haneuse, Sebastien J-P A
2008-04-15
Ecologic (aggregate) data are widely available and widely utilized in epidemiologic studies. However, ecologic bias, which arises because aggregate data cannot characterize within-group variability in exposure and confounder variables, can only be removed by supplementing ecologic data with individual-level data. Here the authors describe the two-phase study design as a framework for achieving this objective. In phase 1, outcomes are stratified by any combination of area, confounders, and error-prone (or discretized) versions of exposures of interest. Phase 2 data, sampled within each phase 1 stratum, provide accurate measures of exposure and possibly of additional confounders. The phase 1 aggregate-level data provide a high level of statistical power and a cross-classification by which individuals may be efficiently sampled in phase 2. The phase 2 individual-level data then provide a control for ecologic bias by characterizing the within-area variability in exposures and confounders. In this paper, the authors illustrate the two-phase study design by estimating the association between infant mortality and birth weight in several regions of North Carolina for 2000-2004, controlling for gender and race. This example shows that the two-phase design removes ecologic bias and produces gains in efficiency over the use of case-control data alone. The authors discuss the advantages and disadvantages of the approach.
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Keller, Matthew C
2014-01-01
Candidate gene × environment (G × E) interaction research tests the hypothesis that the effects of some environmental variable (e.g., childhood maltreatment) on some outcome measure (e.g., depression) depend on a particular genetic polymorphism. Because this research is inherently nonexperimental, investigators have been rightly concerned that detected interactions could be driven by confounders (e.g., ethnicity, gender, age, socioeconomic status) rather than by the specified genetic or environmental variables per se. In an attempt to eliminate such alternative explanations for detected G × E interactions, investigators routinely enter the potential confounders as covariates in general linear models. However, this practice does not control for the effects these variables might have on the G × E interaction. Rather, to properly control for confounders, researchers need to enter the covariate × environment and the covariate × gene interaction terms in the same model that tests the G × E term. In this manuscript, I demonstrate this point analytically and show that the practice of improperly controlling for covariates is the norm in the G × E interaction literature to date. Thus, many alternative explanations for G × E findings that investigators had thought were eliminated have not been. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.
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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
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Solar radiation increases suicide rate after adjusting for other climate factors in South Korea.
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.
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How Confounder Strength Can Affect Allocation of Resources in Electronic Health Records.
Lynch, Kristine E; Whitcomb, Brian W; DuVall, Scott L
2018-01-01
When electronic health record (EHR) data are used, multiple approaches may be available for measuring the same variable, introducing potentially confounding factors. While additional information may be gleaned and residual confounding reduced through resource-intensive assessment methods such as natural language processing (NLP), whether the added benefits offset the added cost of the additional resources is not straightforward. We evaluated the implications of misclassification of a confounder when using EHRs. Using a combination of simulations and real data surrounding hospital readmission, we considered smoking as a potential confounder. We compared ICD-9 diagnostic code assignment, which is an easily available measure but has the possibility of substantial misclassification of smoking status, with NLP, a method of determining smoking status that more expensive and time-consuming than ICD-9 code assignment but has less potential for misclassification. Classification of smoking status with NLP consistently produced less residual confounding than the use of ICD-9 codes; however, when minimal confounding was present, differences between the approaches were small. When considerable confounding is present, investing in a superior measurement tool becomes advantageous.
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Ho, Hung Chak; Lau, Kevin Ka-Lun; Yu, Ruby; Wang, Dan; Woo, Jean; Kwok, Timothy Chi Yui; Ng, Edward
2017-08-31
Previous studies found a relationship between geriatric depression and social deprivation. However, most studies did not include environmental factors in the statistical models, introducing a bias to estimate geriatric depression risk because the urban environment was found to have significant associations with mental health. We developed a cross-sectional study with a binomial logistic regression to examine the geriatric depression risk of a high-density city based on five social vulnerability factors and four environmental measures. We constructed a socio-environmental vulnerability index by including the significant variables to map the geriatric depression risk in Hong Kong, a high-density city characterized by compact urban environment and high-rise buildings. Crude and adjusted odds ratios (ORs) of the variables were significantly different, indicating that both social and environmental variables should be included as confounding factors. For the comprehensive model controlled by all confounding factors, older adults who were of lower education had the highest geriatric depression risks (OR: 1.60 (1.21, 2.12)). Higher percentage of residential area and greater variation in building height within the neighborhood also contributed to geriatric depression risk in Hong Kong, while average building height had negative association with geriatric depression risk. In addition, the socio-environmental vulnerability index showed that higher scores were associated with higher geriatric depression risk at neighborhood scale. The results of mapping and cross-section model suggested that geriatric depression risk was associated with a compact living environment with low socio-economic conditions in historical urban areas in Hong Kong. In conclusion, our study found a significant difference in geriatric depression risk between unadjusted and adjusted models, suggesting the importance of including environmental factors in estimating geriatric depression risk. We also developed a framework to map geriatric depression risk across a city, which can be used for identifying neighborhoods with higher risk for public health surveillance and sustainable urban planning.
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Lau, Kevin Ka-Lun; Yu, Ruby; Wang, Dan; Kwok, Timothy Chi Yui; Ng, Edward
2017-01-01
Previous studies found a relationship between geriatric depression and social deprivation. However, most studies did not include environmental factors in the statistical models, introducing a bias to estimate geriatric depression risk because the urban environment was found to have significant associations with mental health. We developed a cross-sectional study with a binomial logistic regression to examine the geriatric depression risk of a high-density city based on five social vulnerability factors and four environmental measures. We constructed a socio-environmental vulnerability index by including the significant variables to map the geriatric depression risk in Hong Kong, a high-density city characterized by compact urban environment and high-rise buildings. Crude and adjusted odds ratios (ORs) of the variables were significantly different, indicating that both social and environmental variables should be included as confounding factors. For the comprehensive model controlled by all confounding factors, older adults who were of lower education had the highest geriatric depression risks (OR: 1.60 (1.21, 2.12)). Higher percentage of residential area and greater variation in building height within the neighborhood also contributed to geriatric depression risk in Hong Kong, while average building height had negative association with geriatric depression risk. In addition, the socio-environmental vulnerability index showed that higher scores were associated with higher geriatric depression risk at neighborhood scale. The results of mapping and cross-section model suggested that geriatric depression risk was associated with a compact living environment with low socio-economic conditions in historical urban areas in Hong Kong. In conclusion, our study found a significant difference in geriatric depression risk between unadjusted and adjusted models, suggesting the importance of including environmental factors in estimating geriatric depression risk. We also developed a framework to map geriatric depression risk across a city, which can be used for identifying neighborhoods with higher risk for public health surveillance and sustainable urban planning. PMID:28858265
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A community study on emotional distress among Arab and Jewish Israelis over the age of 60.
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.
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Field, Matt; Gage, Suzanne; Hammerton, Gemma; Heron, Jon; Hickman, Matt; Munafò, Marcus R
2018-01-01
Abstract Aims The study aimed to examine the association between adolescent alcohol use and working memory (WM) using a large population sample. Methods Data from the Avon Longitudinal Study of Parents and Children were used to investigate the association between alcohol use at age 15 years and WM 3 years later, assessed using the N-back task (N ~ 3300). A three-category ordinal variable captured mutually exclusive alcohol groupings ranging in order of severity (i.e. low alcohol users, frequent drinkers and frequent/binge drinkers). Differential dropout was accounted for using multiple imputation and inverse probability weighting. Adjustment was made for potential confounders. Results There was evidence of an association between frequent/binge drinking (compared to the low alcohol group) and poorer performance on the 3-back task after adjusting for sociodemographic confounding variables, WM at age 11 years, and experience of a head injury/unconsciousness before age 11 years (β = −0.23, 95% CI = −0.37 to −0.09, P = 0.001). However, this association was attenuated (β = −0.12, 95% CI = −0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly cigarette tobacco and cannabis use. Weaker associations were found for the less demanding 2-back task. We found no evidence to suggest frequent drinking was associated with performance on either task. Conclusions We found weak evidence of an association between sustained heavy alcohol use in mid-adolescence and impaired WM 3 years later. Although we cannot fully rule out the possibility of reverse causation, several potential confounding variables were included to address the directionality of the relationship between WM and alcohol use problems. PMID:29329371
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Mahedy, Liam; Field, Matt; Gage, Suzanne; Hammerton, Gemma; Heron, Jon; Hickman, Matt; Munafò, Marcus R
2018-05-01
The study aimed to examine the association between adolescent alcohol use and working memory (WM) using a large population sample. Data from the Avon Longitudinal Study of Parents and Children were used to investigate the association between alcohol use at age 15 years and WM 3 years later, assessed using the N-back task (N ~ 3300). A three-category ordinal variable captured mutually exclusive alcohol groupings ranging in order of severity (i.e. low alcohol users, frequent drinkers and frequent/binge drinkers). Differential dropout was accounted for using multiple imputation and inverse probability weighting. Adjustment was made for potential confounders. There was evidence of an association between frequent/binge drinking (compared to the low alcohol group) and poorer performance on the 3-back task after adjusting for sociodemographic confounding variables, WM at age 11 years, and experience of a head injury/unconsciousness before age 11 years (β = -0.23, 95% CI = -0.37 to -0.09, P = 0.001). However, this association was attenuated (β = -0.12, 95% CI = -0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly cigarette tobacco and cannabis use. Weaker associations were found for the less demanding 2-back task. We found no evidence to suggest frequent drinking was associated with performance on either task. We found weak evidence of an association between sustained heavy alcohol use in mid-adolescence and impaired WM 3 years later. Although we cannot fully rule out the possibility of reverse causation, several potential confounding variables were included to address the directionality of the relationship between WM and alcohol use problems.
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Pregnant women with the sickle cell trait are not at increased risk for developing preeclampsia.
Stamilio, David M; Sehdev, Harish M; Macones, George A
2003-01-01
The primary objective of this study was to determine whether having the sickle cell trait is independently associated with preeclampsia. We performed a retrospective cohort study of 1998 pregnant patients who either did or did not have the sickle cell trait. All patients were screened for the sickle trait using the "Sickledex" test. Data on neonatal and maternal outcome, including preeclampsia, and potential confounding variables were abstracted from medical records. Unadjusted, stratified, and multiple logistic regression analyses were used to identify interactions, and confounding between multiple variables and the association between sickle cell trait and preeclampsia. With an anticipated 6.5% rate of preeclampsia, and alpha = 0.05, this cohort study has 80% power to detect a relative risk (RR) of 2.3 for preeclampsia. Univariate analysis revealed that the two cohorts were similar with regard to primiparity, maternal age, chronic diseases, birth weight, and gestational age at delivery, but the sickle cell trait cohort was more likely to have gestational diabetes and had a higher mean body mass index (BMI). In the univariate analysis, the sickle cell trait cohort was not at increased risk for preeclampsia [unadjusted RR = 0.5, 95% CI (0.2-1.6)]. After controlling for potential confounding variables with logistic regression analysis, sickle trait was not independently associated with preeclampsia [adjusted RR = 0.5, 95% CI (0.2- 1.6)]. In contrast to prior work, these data suggest that the sickle cell trait is not an independent risk factor for preeclampsia or postpartum complications. In fact, the data are more consistent with the sickle trait being protective for developing preeclampsia.
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Geeleher, Paul; Cox, Nancy J; Huang, R Stephanie
2016-09-21
We show that variability in general levels of drug sensitivity in pre-clinical cancer models confounds biomarker discovery. However, using a very large panel of cell lines, each treated with many drugs, we could estimate a general level of sensitivity to all drugs in each cell line. By conditioning on this variable, biomarkers were identified that were more likely to be effective in clinical trials than those identified using a conventional uncorrected approach. We find that differences in general levels of drug sensitivity are driven by biologically relevant processes. We developed a gene expression based method that can be used to correct for this confounder in future studies.
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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
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Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A
2017-08-17
To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.
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Supervised normalization of microarrays
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
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Honings, S; Drukker, M; Groen, R; van Os, J
2016-01-01
Recent studies suggest that psychotic experiences (PE) in the general population are associated with an increased risk of self-injurious behaviour. Both the magnitude of this association and the level of adjustment for confounders vary among studies. A meta-analysis was performed to integrate the available evidence. The influence of possible confounders, including variably defined depression, was assessed. A systematic review and meta-analysis was conducted including general population studies reporting on the risk of self-injurious behaviour in individuals with PE. Studies were identified by a systematic search strategy in Pubmed, PsycINFO and Embase. Reported effect sizes were extracted and meta-analytically pooled. The risk of self-injurious behaviour was 3.20 times higher in individuals with PE compared with those without. Subanalyses showed that PE were associated with self-harm, suicidal ideation as well as suicidal attempts. All studies had scope for considerable residual confounding; effect sizes adjusted for depression were significantly smaller than effect sizes unadjusted for depression. In the longitudinal studies, adjustment for psychopathology resulted in a 74% reduction in excess risk. PE are associated with self-injurious behaviour, suggesting they have potential as passive markers of suicidality. However, the association is confounded and several methodological issues remain, particularly how to separate PE from the full range of connected psychopathology in determining any specific association with self-injurious behaviour. Given evidence that PE represent an indicator of severity of non-psychotic psychopathology, the association between PE and self-injurious behaviour probably reflects a greater likelihood of self-injurious behaviour in more severe states of mental distress.
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DeBruine, Lisa M; Jones, Benedict C; Smith, Finlay G; Little, Anthony C
2010-06-01
Women's preferences for male masculinity are highly variable. Although many researchers explain this variability as reflecting systematic individual differences in how women resolve the tradeoff between the costs and benefits of choosing a masculine partner, others suggest that methodological differences between studies are responsible. A recent study found general femininity preferences for judgments of faces that were manipulated in sexual dimorphism of shape but general masculinity preferences for judgments of faces that were based on perceived masculinity. Using the original stimuli, we replicated these previous results but found equivalent general femininity preferences for both types of faces when nonface confounds in the stimuli (e.g. hairstyle) were eliminated through masking. We conclude that care must be taken to control potential confounds in stimuli and that the influence of nonface cues on preferences for facial masculinity deserves further study.
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Eliminating Survivor Bias in Two-stage Instrumental Variable Estimators.
Vansteelandt, Stijn; Walter, Stefan; Tchetgen Tchetgen, Eric
2018-07-01
Mendelian randomization studies commonly focus on elderly populations. This makes the instrumental variables analysis of such studies sensitive to survivor bias, a type of selection bias. A particular concern is that the instrumental variable conditions, even when valid for the source population, may be violated for the selective population of individuals who survive the onset of the study. This is potentially very damaging because Mendelian randomization studies are known to be sensitive to bias due to even minor violations of the instrumental variable conditions. Interestingly, the instrumental variable conditions continue to hold within certain risk sets of individuals who are still alive at a given age when the instrument and unmeasured confounders exert additive effects on the exposure, and moreover, the exposure and unmeasured confounders exert additive effects on the hazard of death. In this article, we will exploit this property to derive a two-stage instrumental variable estimator for the effect of exposure on mortality, which is insulated against the above described selection bias under these additivity assumptions.
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Vega-Franco, L; Mejía, A M; Robles, B; Moreno, L; Pérez, Y
1991-11-01
This study gave us the opportunity to know the roles iron deficiency and the presence of lead in blood play, as confounding variables, in relation to the state of malnutrition and the intellect of those children. A sample of 169 school children were classified according to their state of nutrition, their condition in reference to serum iron and lead concentrations. In addition, their intelligence was evaluated. The results confirmed that those children with lower weights and heights registered lesser points of intelligence; in fact, iron deficiency cancels out the difference in favor of those taller and weighing more. Lead did not contribute as a confounding variable, but more than half of the children showed possible toxic levels of this metal.
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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.
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Toward a clearer portrayal of confounding bias in instrumental variable applications.
Jackson, John W; Swanson, Sonja A
2015-07-01
Recommendations for reporting instrumental variable analyses often include presenting the balance of covariates across levels of the proposed instrument and levels of the treatment. However, such presentation can be misleading as relatively small imbalances among covariates across levels of the instrument can result in greater bias because of bias amplification. We introduce bias plots and bias component plots as alternative tools for understanding biases in instrumental variable analyses. Using previously published data on proposed preference-based, geography-based, and distance-based instruments, we demonstrate why presenting covariate balance alone can be problematic, and how bias component plots can provide more accurate context for bias from omitting a covariate from an instrumental variable versus non-instrumental variable analysis. These plots can also provide relevant comparisons of different proposed instruments considered in the same data. Adaptable code is provided for creating the plots.
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Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide
Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.
2014-01-01
A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327
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Acute alcohol consumption, alcohol outlets, and gun suicide.
Branas, Charles C; Richmond, Therese S; Ten Have, Thomas R; Wiebe, Douglas J
2011-01-01
A case-control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed.
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Wen, Xiaopiao; Liang, Yuan; Zhu, Jiang; Wu, Tangchun
2013-01-01
The aim of the current study was to explore the relationship between housework and health of retired older adults, and to provide new evidences and clues for the effects of housework on health. The data came from the baseline survey of the Tongji-Dongfeng Cohort Study with 25,501 participants. The independent variable was housework including child care, elder care, grocery shopping & cooking, and washing clothes & cleaning house. The dependent variable was self-reported two-week illness. Age, education, marital status, smoking and drinking were used as potential confounding variables. There are gender differences in the four types of housework, with higher prevalence among women than among men. The prevalence of two-week illness in women was higher than that in men. After adjusting for potential confounding variables, the four types of housework had almost no significant effects on two-week illness, except for washing clothes & cleaning house with a negative effect for women (OR = 1.17, 95% CI 1.06-1.29). The association of housework with health, especially of child care, elder care, and grocery shopping & cooking without significance and of washing clothes & cleaning house with significance for women, would provide a valuable clue for in-depth study of housework, namely the effects of housework on health would be subdivided into the dimensions of psychological and social activity besides physical activity, and it may not be suitable to simply classify housework as a kind of exercise.
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Comparison of methods for the analysis of relatively simple mediation models.
Rijnhart, Judith J M; Twisk, Jos W R; Chinapaw, Mai J M; de Boer, Michiel R; Heymans, Martijn W
2017-09-01
Statistical mediation analysis is an often used method in trials, to unravel the pathways underlying the effect of an intervention on a particular outcome variable. Throughout the years, several methods have been proposed, such as ordinary least square (OLS) regression, structural equation modeling (SEM), and the potential outcomes framework. Most applied researchers do not know that these methods are mathematically equivalent when applied to mediation models with a continuous mediator and outcome variable. Therefore, the aim of this paper was to demonstrate the similarities between OLS regression, SEM, and the potential outcomes framework in three mediation models: 1) a crude model, 2) a confounder-adjusted model, and 3) a model with an interaction term for exposure-mediator interaction. Secondary data analysis of a randomized controlled trial that included 546 schoolchildren. In our data example, the mediator and outcome variable were both continuous. We compared the estimates of the total, direct and indirect effects, proportion mediated, and 95% confidence intervals (CIs) for the indirect effect across OLS regression, SEM, and the potential outcomes framework. OLS regression, SEM, and the potential outcomes framework yielded the same effect estimates in the crude mediation model, the confounder-adjusted mediation model, and the mediation model with an interaction term for exposure-mediator interaction. Since OLS regression, SEM, and the potential outcomes framework yield the same results in three mediation models with a continuous mediator and outcome variable, researchers can continue using the method that is most convenient to them.
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Using ecological propensity score to adjust for missing confounders in small area studies.
Wang, Yingbo; Pirani, Monica; Hansell, Anna L; Richardson, Sylvia; Blangiardo, Marta
2017-11-09
Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London. © The Author 2017. Published by Oxford University Press.
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Farbu, Jorunn; Haugen, Margaretha; Meltzer, Helle Margrete; Brantsæter, Anne Lise
2014-12-05
Little attention has been given to the impact of singlehood during pregnancy. The aim of this study was to examine the impact of marital status on diet during pregnancy and pregnancy outcome. The study population comprised 62,773 women participating in the Norwegian Mother and Child Cohort Study. Marital status was categorised into singles living alone, singles living with parents and married/cohabiting (reference group). Participants answered a general health questionnaire in gestational week 15-17 and a food frequency questionnaire in gestational week 22. We used nonparametric tests to compare dietary intakes by marital status, and multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for infants being small for gestational age (SGA), large for gestational age (LGA), and preterm delivery (defined as delivery before gestational week 37). Single women living with parents had lower intakes of fruits and vegetables, higher intake of total energy, higher proportion of energy from added sugar, and lower intake of fibre than the reference group. Singles living alone also had a higher intake of added sugar. In both of the single groups, daily smoking was more prevalent than in women living with a partner. In analyses adjusted for maternal age, pre-pregnancy BMI, energy intake, energy contributed by protein, education, income, parity and nausea, single women living alone had increased risk of SGA with OR = 1.27 (95% CI: 1.05, 1.55). When smoking was included among the confounding variables, the association was no longer significant. Likewise, singles living alone had increased risk of preterm delivery, with OR = 1.32 (95% CI: 1.01, 1.72) in a partly adjusted model, but the association did not remain significant in a model fully adjusted for confounding variables. Single mothers had lower dietary quality and included more smokers than women who lived with a partner. Single mothers living alone had higher prevalence of SGA and preterm delivery, but the associations with adverse pregnancy outcomes were confounded by other variables. This study shows that single mothers should be given special attention during antenatal care and counselling.
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The Combined Effects of Measurement Error and Omitting Confounders in the Single-Mediator Model
Fritz, Matthew S.; Kenny, David A.; MacKinnon, David P.
2016-01-01
Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator to outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. In order to explore the combined effect of measurement error and omitted confounders in the same model, the impact of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect. PMID:27739903
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Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data
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
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Lasserson, Daniel S; Scherpbier de Haan, Nynke; de Grauw, Wim; van der Wel, Mark; Wetzels, Jack F; O'Callaghan, Christopher A
2016-06-10
To determine the relationship between renal function and visit-to-visit blood pressure (BP) variability in a cohort of primary care patients. Retrospective cohort study from routinely collected healthcare data. Primary care in Nijmegen, the Netherlands, from 2007 to 2012. 19 175 patients who had a measure of renal function, and 7 separate visits with BP readings in the primary care record. Visit-to-visit variability in systolic BP, calculated from the first 7 office measurements, including SD, successive variation, absolute real variation and metrics of variability shown to be independent of mean. Multiple linear regression was used to analyse the influence of estimated glomerular filtration rate (eGFR) on BP variability measures with adjustment for age, sex, diabetes, mean BP, proteinuria, cardiovascular disease, time interval between measures and antihypertensive use. In the patient cohort, 57% were women, mean (SD) age was 65.5 (12.3) years, mean (SD) eGFR was 75.6 (18.0) mL/min/1.73m(2) and SD systolic BP 148.3 (21.4) mm Hg. All BP variability measures were negatively correlated with eGFR and positively correlated with age. However, multiple linear regressions demonstrated consistent, small magnitude negative relationships between eGFR and all measures of BP variability adjusting for confounding variables. Worsening renal function is associated with small increases in measures of visit-to-visit BP variability after adjustment for confounding factors. This is seen across the spectrum of renal function in the population, and provides a mechanism whereby chronic kidney disease may raise the risk of cardiovascular events. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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On the definition of a confounder
VanderWeele, Tyler J.; Shpitser, Ilya
2014-01-01
Summary The causal inference literature has provided a clear formal definition of confounding expressed in terms of counterfactual independence. The causal inference literature has not, however, produced a clear formal definition of a confounder, as it has given priority to the concept of confounding over that of a confounder. We consider a number of candidate definitions arising from various more informal statements made in the literature. We consider the properties satisfied by each candidate definition, principally focusing on (i) whether under the candidate definition control for all “confounders” suffices to control for “confounding” and (ii) whether each confounder in some context helps eliminate or reduce confounding bias. Several of the candidate definitions do not have these two properties. Only one candidate definition of those considered satisfies both properties. We propose that a “confounder” be defined as a pre-exposure covariate C for which there exists a set of other covariates X such that effect of the exposure on the outcome is unconfounded conditional on (X, C) but such that for no proper subset of (X, C) is the effect of the exposure on the outcome unconfounded given the subset. A variable that helps reduce bias but not eliminate bias we propose referring to as a “surrogate confounder.” PMID:25544784
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Assessing Omitted Confounder Bias in Multilevel Mediation Models.
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.
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Confounder Detection in High-Dimensional Linear Models Using First Moments of Spectral Measures.
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.
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Overview of clinical research design.
Hartung, Daniel M; Touchette, Daniel
2009-02-15
Basic concepts and terminology of clinical research design are presented for new clinical investigators. Clinical research, research involving human subjects, can be described as either observational or experimental. The findings of all clinical research can be threatened by issues of bias and confounding. Biases are systematic errors in how study subjects are selected or measured, which result in false inferences. Confounding is a distortion in findings that is attributable to mixing variable effects. Uncontrolled observation research is generally more prone to bias and confounding than experimental research. Observational research includes designs such as the cohort study, case-control study, and cross-sectional study, while experimental research typically involves a randomized controlled trial (RCT). The cohort study, which includes the RCT, defines subject allocation on the basis of exposure interest (e.g., drug, disease-management program) and follows the patients to assess the outcomes. The case-control study uses the primary outcome of interest (e.g., adverse event) to define subject allocation, and different exposures are assessed in a retrospective manner. Cross-sectional research evaluates both exposure and outcome concurrently. Each of these design methods possesses different strengths and weaknesses in answering research questions, as well as underlying many study subtypes. While experimental research is the strongest method for establishing causality, it can be difficult to accomplish under many scenarios. Observational clinical research offers many design alternatives that may be appropriate if planned and executed carefully.
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Lee, Paul H
2017-06-01
Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the estimation of a causal relationship between the exposure and outcome in 3 ways: using a linear term, binning into 5 equal-size categories, or using a restricted cubic spline of the confounder. Continuous, binary, and survival outcomes were simulated. We examined the confounder across varying measurement error. In addition, we performed a real data analysis examining the 3 strategies to handle the nonlinear effects of accelerometer-measured physical activity in the National Health and Nutrition Examination Survey 2003-2006 data. The mis-specification of a nonlinear confounder had little impact on causal effect estimation for continuous outcomes. For binary and survival outcomes, this mis-specification introduced bias, which could be eliminated using spline adjustment only when there is small measurement error of the confounder. Real data analysis showed that the associations between high blood pressure, high cholesterol, and diabetes and mortality adjusted for physical activity with restricted cubic spline were about 3% to 11% larger than their counterparts adjusted with a linear term. For continuous outcomes, confounders with nonlinear effects can be adjusting with a linear term. Spline adjustment should be used for binary and survival outcomes on confounders with small measurement error.
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Grimm, Lars J; Bookhout, Christine E; Bentley, Rex C; Jordan, Sheryl G; Lawton, Thomas J
2018-05-01
Non-atypical papillomas (NAPs) diagnosed on core needle biopsy (CNB) frequently undergo surgical excision due to highly variable upstaging rates. The purpose of this study is to document our dual-institution upgrade rates of NAPs diagnosed on core needle biopsy and review the upgrade rates reported in the literature. Following IRB approval, CNB results from Duke University (7/1/2004-6/30/2014) and the University of North Carolina Chapel Hill (1/1/04-6/30/2013) were reviewed to identify non-atypical papillomas. All cases with surgical excision or 2 years of imaging follow up were included. In addition, a literature review identified 60 published studies on upgrades of NAPs diagnosed at CNB. Cases in our cohort and the published literature were reviewed for confounding factors: [1] missing radiologic-pathologic concordance and/or discordance, [2] papillomas included with high-risk lesions, [3] high risk lesions counted as upgrades, [4] review by a nonspecialized breast pathologist, and [5] cancer incidentally detected. Of the 388 CNBs in our dual-institution cohort, 136 (35%) patients underwent surgical excision and 252 (65%) patients had imaging follow up. After controlling for confounders, no cancers (0/388) were found at surgical excision or during follow up imaging. The literature review upstaging rate was 4.0% (166/4157) but 1.8% (4/227) after excluding studies with confounders. The combined upstaging rate from the literature and this study was 0.6% (4/615). The upstaging rate for CNB diagnosed NAPs was 0% in our cohort and 0.6% overall after adjusting for confounders. This low rate does not warrant reflexive surgical excision and diagnostic imaging follow up should be discretionary. Copyright © 2018 Elsevier Inc. All rights reserved.
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Cacace, Anthony T; McFarland, Dennis J
2013-01-01
Tests of auditory perception, such as those used in the assessment of central auditory processing disorders ([C]APDs), represent a domain in audiological assessment where measurement of this theoretical construct is often confounded by nonauditory abilities due to methodological shortcomings. These confounds include the effects of cognitive variables such as memory and attention and suboptimal testing paradigms, including the use of verbal reproduction as a form of response selection. We argue that these factors need to be controlled more carefully and/or modified so that their impact on tests of auditory and visual perception is only minimal. To advocate for a stronger theoretical framework than currently exists and to suggest better methodological strategies to improve assessment of auditory processing disorders (APDs). Emphasis is placed on adaptive forced-choice psychophysical methods and the use of matched tasks in multiple sensory modalities to achieve these goals. Together, this approach has potential to improve the construct validity of the diagnosis, enhance and develop theory, and evolve into a preferred method of testing. Examination of methods commonly used in studies of APDs. Where possible, currently used methodology is compared to contemporary psychophysical methods that emphasize computer-controlled forced-choice paradigms. In many cases, the procedures used in studies of APD introduce confounding factors that could be minimized if computer-controlled forced-choice psychophysical methods were utilized. Ambiguities of interpretation, indeterminate diagnoses, and unwanted confounds can be avoided by minimizing memory and attentional demands on the input end and precluding the use of response-selection strategies that use complex motor processes on the output end. Advocated are the use of computer-controlled forced-choice psychophysical paradigms in combination with matched tasks in multiple sensory modalities to enhance the prospect of obtaining a valid diagnosis. American Academy of Audiology.
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Covariate selection with group lasso and doubly robust estimation of causal effects
Koch, Brandon; Vock, David M.; Wolfson, Julian
2017-01-01
Summary The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this paper, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry. PMID:28636276
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Covariate selection with group lasso and doubly robust estimation of causal effects.
Koch, Brandon; Vock, David M; Wolfson, Julian
2018-03-01
The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this article, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry. © 2017, The International Biometric Society.
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ERIC Educational Resources Information Center
Bollen, Kenneth A.
2007-01-01
R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal…
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Causal diagrams and multivariate analysis III: confound it!
Jupiter, Daniel C
2015-01-01
This commentary concludes my series concerning inclusion of variables in multivariate analyses. We take up the issues of confounding and effect modification and summarize the work we have thus far done. Finally, we provide a rough algorithm to help guide us through the maze of possibilities that we have outlined. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
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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.
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Polychlorinated biphenyl exposure and effects in transformer repair workers.
Emmett, E A
1985-01-01
Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower. Statistically significant differences in serum albumin and lactic dehydrogenase, but not in other liver function tests, were seen between the exposed and comparison groups; however, after adjustment for confounding variables, no correlations were observed between liver function tests and either adipose or serum PCBs concentrations. Statistically significant correlation both before and after adjustment for confounding variables were seen with adipose PCBs and 24-hr urinary 17-hydroxycorticosteroid excretion and with serum PCBs and serum gamma-glutamyl transpeptidase. Both associations could reflect microsomal enzyme induction among other possibilities. No differences were seen in fasting serum triglycerides, total cholesterol, LDL, HDL or VLDL cholesterol between the two exposure groups. A statistically significant correlation between serum PCBs and serum triglycerides, total cholesterol, and VLDL cholesterol was removed by adjusting for confounding variables. No correlation was seen between adipose PCBs concentrations and any serum lipid component. Partition phenomena could account for these findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2863134
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On causal interpretation of race in regressions adjusting for confounding and mediating variables
VanderWeele, Tyler J.; Robinson, Whitney R.
2014-01-01
We consider several possible interpretations of the “effect of race” when regressions are run with race as an exposure variable, controlling also for various confounding and mediating variables. When adjustment is made for socioeconomic status early in a person’s life, we discuss under what contexts the regression coefficients for race can be interpreted as corresponding to the extent to which a racial inequality would remain if various socioeconomic distributions early in life across racial groups could be equalized. When adjustment is also made for adult socioeconomic status, we note how the overall racial inequality can be decomposed into the portion that would be eliminated by equalizing adult socioeconomic status across racial groups and the portion of the inequality that would remain even if adult socioeconomic status across racial groups were equalized. We also discuss a stronger interpretation of the “effect of race” (stronger in terms of assumptions) involving the joint effects of race-associated physical phenotype (e.g. skin color), parental physical phenotype, genetic background and cultural context when such variables are thought to be hypothetically manipulable and if adequate control for confounding were possible. We discuss some of the challenges with such an interpretation. Further discussion is given as to how the use of selected populations in examining racial disparities can additionally complicate the interpretation of the effects. PMID:24887159
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Periodontitis is associated with diabetic retinopathy in non-obese adults.
Song, Su Jeong; Lee, Seong-Su; Han, Kyungdo; Park, Jun-Beom
2017-04-01
Patients with diabetes retinopathy appear to show increased susceptibility to periodontal disease. This study was performed to assess the relationship between periodontitis and the prevalence of diabetic retinopathy in a large probability sample of the Korean population. A subgroup analysis was performed using body mass index <25 kg/m 2 as the criterion to evaluate the effect of obesity on this relationship. This study is based on data from the Korean National Health and Nutrition Examination Survey of the Korean population, conducted between 2008 and 2010. The presence of diabetic retinopathy in relation to demographic variables and anthropometric characteristics of the participants is presented as means with their standard errors. The presence of periodontitis and presence of retinopathy categorized by body mass index (<25 and ≥25 kg/m 2 ) were evaluated. Multiple logistic regression analyses were used to assess the associations between periodontitis and diabetic retinopathy after adjustment with variables, including age, sex, smoking, drinking, exercise, hypertension, metabolic syndrome, HbA1c, and duration of diabetes mellitus. There was a statistically significant increase in the prevalence of periodontitis in individuals who had proliferative diabetic retinopathy. The odds ratios [95% confidence intervals] of prevalence of diabetic retinopathy were 1.193 [0.757-1.881] for the whole population after adjustments with confounding factors. Subgroup analysis after adjustments with confounding factors showed that the odds ratios [95% confidence intervals] of prevalence were 2.206 [1.114-4.366] and 0.588 [0.326-1.061] among participants with body mass index <25 kg/m 2 and body mass index 37 ≥25 kg/m 2 , respectively. The diabetic retinopathy was positively associated with the presence of periodontitis in non-obese diabetic Korean adults after adjustment with confounding variables. Our findings suggest that when a periodontist finds the presence of periodontitis in non-obese diabetic patients, timely evaluation of the patient's ophthalmic evaluation should be 44 recommended.
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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.
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de Vocht, Frank; Lee, Brian
2014-08-01
Studies have suggested that residential exposure to extremely low frequency (50 Hz) electromagnetic fields (ELF-EMF) from high voltage cables, overhead power lines, electricity substations or towers are associated with reduced birth weight and may be associated with adverse birth outcomes or even miscarriages. We previously conducted a study of 140,356 singleton live births between 2004 and 2008 in Northwest England, which suggested that close residential proximity (≤ 50 m) to ELF-EMF sources was associated with reduced average birth weight of 212 g (95%CI: -395 to -29 g) but not with statistically significant increased risks for other adverse perinatal outcomes. However, the cohort was limited by missing data for most potentially confounding variables including maternal smoking during pregnancy, which was only available for a small subgroup, while also residual confounding could not be excluded. This study, using the same cohort, was conducted to minimize the effects of these problems using multiple imputation to address missing data and propensity score matching to minimize residual confounding. Missing data were imputed using multiple imputation using chained equations to generate five datasets. For each dataset 115 exposed women (residing ≤ 50 m from a residential ELF-EMF source) were propensity score matched to 1150 unexposed women. After doubly robust confounder adjustment, close proximity to a residential ELF-EMF source remained associated with a reduction in birth weight of -116 g (95% confidence interval: -224:-7 g). No effect was found for proximity ≤ 100 m compared to women living further away. These results indicate that although the effect size was about half of the effect previously reported, close maternal residential proximity to sources of ELF-EMF remained associated with suboptimal fetal growth. Copyright © 2014 Elsevier Ltd. All rights reserved.
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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.
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Pedraza-Flechas, Ana María; Lope, Virginia; Moreo, Pilar; Ascunce, Nieves; Miranda-García, Josefa; Vidal, Carmen; Sánchez-Contador, Carmen; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Llobet, Rafael; Aragonés, Nuria; Salas-Trejo, Dolores; Pollán, Marina; Pérez-Gómez, Beatriz
2017-05-01
We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (e β :1.53;95%CI:1.04-2.26). Copyright © 2017 Elsevier B.V. All rights reserved.
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Delpierre, C; Fantin, R; Barboza-Solis, C; Lepage, B; Darnaudéry, M; Kelly-Irving, M
2016-08-18
Lifecourse studies suggest that the metabolic syndrome (MetS) may be rooted in the early life environment. This study aims to examine the pathways linking early nutritional and psychosocial exposures and the presence of MetS in midlife. Data are from the National Child Development Study including individuals born during 1 week in 1958 in Great Britain and followed-up until now. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III classification. Mother's pre-pregnancy body mass index (BMI) was used as a proxy of the early nutritional environment and Adverse Childhood Experiences (ACE) as a proxy for early psychosocial stress. Socioeconomic characteristics, pregnancy and birth conditions were extracted as potential confounders. Adult health behaviors, BMI, socioeconomic environment and psychological state were considered as mediating variables. Multivariate models were performed by including variables sequentially taking a lifecourse approach. 37.5 % of men and 19.8 % of women had MetS. Participants with an obese/overweight mother presented a higher risk of MetS than those whose mother had a normal pre-pregnancy BMI. Men exposed to two ACE or more, and women exposed to one ACE, were more at risk of MetS compared to unexposed individuals. After including confounders and mediators, mother's pre-pregnancy BMI was still associated with MetS in midlife but the association was weakened after including participant's adult BMI. ACE was no longer associated with MetS after including confounders in models. The early nutritional environment, represented by mother's pre-pregnancy BMI, was associated with the risk of MetS in midlife. An important mechanism involves a mother-to-child BMI transmission, independent of birth or perinatal conditions, socioeconomic characteristics and health behaviors over the lifecourse. However this mechanism is not sufficient for explaining the influence of mother's pre-pregnancy BMI which implies the need to further explore other mechanisms in particular the role of genetics and early nutritional environment. ACE is not independently associated with MetS. However, other early life stressful events such as emergency caesarean deliveries and poor socioeconomic status during childhood may contribute as determinants of MetS.
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Temperature variability during delirium in ICU patients: an observational study.
van der Kooi, Arendina W; Kappen, Teus H; Raijmakers, Rosa J; Zaal, Irene J; Slooter, Arjen J C
2013-01-01
Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and -nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. We included patients who experienced both delirium and delirium free days during ICU stay, based on the Confusion Assessment method for the ICU conducted by a research- physician or -nurse, in combination with inspection of medical records. We excluded patients with conditions affecting thermal regulation or therapies affecting body temperature. Daily temperature variability was determined by computing the mean absolute second derivative of the temperature signal. Temperature variability (primary outcome) and absolute body temperature (secondary outcome) were compared between delirium- and non-delirium days with a linear mixed model and adjusted for daily mean Richmond Agitation and Sedation Scale scores and daily maximum Sequential Organ Failure Assessment scores. Temperature variability was increased during delirium-days compared to days without delirium (β(unadjuste)d=0.007, 95% confidence interval (CI)=0.004 to 0.011, p<0.001). Adjustment for confounders did not alter this result (β(adjusted)=0.005, 95% CI=0.002 to 0.008, p<0.001). Delirium was not associated with absolute body temperature (β(unadjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.61). This did not change after adjusting for confounders (β(adjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.63). Our study suggests that temperature variability is increased during ICU delirium.
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Environmental confounding in gene-environment interaction studies.
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.
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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
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Sanderson, Eleanor; Macdonald-Wallis, Corrie; Davey Smith, George
2018-01-01
Abstract Background Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome. Methods We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations. Results Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study. Conclusions Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present. PMID:29088358
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Sanderson, Eleanor; Macdonald-Wallis, Corrie; Davey Smith, George
2018-04-01
Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome. We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations. Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study. Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present.
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Oral care experiences and challenges in children with autism spectrum disorders.
Stein, Leah I; Polido, José C; Najera, Sandy Oliver Lopez; Cermak, Sharon A
2012-01-01
The purpose of this study was to investigate the differences between children with autism spectrum disorders (ASD) and their typically developing peers in relation to aspects of oral care. Participants included 396 parents of ASD children or typically developing 2- to 18-year-olds. Parents completed a 37-item questionnaire designed by authors to elicit information about oral care in the home and dental office. Descriptive, bivariate, and multivariate regression analyses were conducted to examine the association between diagnostic group and oral care variables. Significantly more parents of ASD children than parents of typically developing children reported difficulty across almost all oral care variables explored, including oral care in the home, oral care at the dentist, and access to oral care. Following multivariate regression to control for possible confounders-including age, gender, Hispanic status, and paternal education level-all previously significant variables remained significant. This study indicates that children with autism spectrum disorders experience greater difficulties and barriers to care in both the home and dental office settings than their typically developing peers.
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Esh-Broder, Efrat; Oron, Galia; Son, Weon-Young; Holzer, Hananel; Tulandi, Togas
2015-10-01
Maternal serum ß-human chorionic gonadotropin (ß-hCG) represents the trophoblastic cell mass and is an indirect measurement of embryo development at early implantation stage. Studies in animals and human embryos detected sex-related growth differences (SRGD) in favour of male embryos during the pre-implantation period. The purpose of our study was to correlate SRGD and maternal serum ß-hCG at 16 days after embryo transfer. We retrospectively analysed all (fresh and frozen) non-donor, single embryo transfers (SET), elective and not elective, that were performed between December 2008 and December 2013. We included ß-hCG values from day 16 after oocyte collection of pregnancies resulting in live birth. Neonatal gender was retrieved from patient files. Male and female embryos were further grouped to cleavage and blastocyst stage transfers. Regression analysis for confounding variables included maternal age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo quality (grade), assisted hatching, day of transfer and fresh or frozen embryo transfer. Seven hundred eighty-six non-donor SETs resulted in live birth. After including only day 16 serum ß-hCG results, 525 SETs were analysed. Neonatal gender was available for 522 cases. Mean maternal serum ß-hCG levels were similar, 347 ± 191 IU/L in the male newborn group and 371 ± 200 IU/L in the female group. The difference between ß-hCG levels remained insignificant after adjusting for confounding variables. Early maternal ß-hCG levels after embryo transfers did not represent SRGD in our study.
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Religion, a social determinant of mortality? A 10-year follow-up of the Health and Retirement Study
Blevins, John; Kiser, Mimi
2017-01-01
The social determinants of health framework has brought a recognition of the primary importance of social forces in determining population health. Research using this framework to understand the health and mortality impact of social, economic, and political conditions, however, has rarely included religious institutions and ties. We investigate a well-measured set of social and economic determinants along with several measures of religious participation as predictors of adult mortality. Respondents (N = 18,370) aged 50 and older to the Health and Retirement Study were interviewed in 2004 and followed for all-cause mortality to 2014. Exposure variables were religious attendance, importance, and affiliation. Other social determinants of health included gender, race/ethnicity, education, household income, and net worth measured at baseline. Confounders included physical and mental health. Health behaviors and social ties were included as potential explanatory variables. Cox proportional hazards regressions were adjusted for complex sample design. After adjustment for confounders, attendance at religious services had a dose-response relationship with mortality, such that respondents who attended frequently had a 40% lower hazard of mortality (HR = 0.60, 95% CI 0.53–0.68) compared with those who never attended. Those for whom religion was “very important” had a 4% higher hazard (HR = 1.04, 95% CI 1.01–1.07); religious affiliation was not associated with risk of mortality. Higher income and net worth were associated with a reduced hazard of mortality as were female gender, Latino ethnicity, and native birth. Religious participation is multi-faceted and shows both lower and higher hazards of mortality in an adult US sample in the context of a comprehensive set of other social and economic determinants of health. PMID:29261682
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Religion, a social determinant of mortality? A 10-year follow-up of the Health and Retirement Study.
Idler, Ellen; Blevins, John; Kiser, Mimi; Hogue, Carol
2017-01-01
The social determinants of health framework has brought a recognition of the primary importance of social forces in determining population health. Research using this framework to understand the health and mortality impact of social, economic, and political conditions, however, has rarely included religious institutions and ties. We investigate a well-measured set of social and economic determinants along with several measures of religious participation as predictors of adult mortality. Respondents (N = 18,370) aged 50 and older to the Health and Retirement Study were interviewed in 2004 and followed for all-cause mortality to 2014. Exposure variables were religious attendance, importance, and affiliation. Other social determinants of health included gender, race/ethnicity, education, household income, and net worth measured at baseline. Confounders included physical and mental health. Health behaviors and social ties were included as potential explanatory variables. Cox proportional hazards regressions were adjusted for complex sample design. After adjustment for confounders, attendance at religious services had a dose-response relationship with mortality, such that respondents who attended frequently had a 40% lower hazard of mortality (HR = 0.60, 95% CI 0.53-0.68) compared with those who never attended. Those for whom religion was "very important" had a 4% higher hazard (HR = 1.04, 95% CI 1.01-1.07); religious affiliation was not associated with risk of mortality. Higher income and net worth were associated with a reduced hazard of mortality as were female gender, Latino ethnicity, and native birth. Religious participation is multi-faceted and shows both lower and higher hazards of mortality in an adult US sample in the context of a comprehensive set of other social and economic determinants of health.
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Kischkel, Sabine; Miekisch, Wolfram; Sawacki, Annika; Straker, Eva M; Trefz, Phillip; Amann, Anton; Schubert, Jochen K
2010-11-11
Up to now, none of the breath biomarkers or marker sets proposed for cancer recognition has reached clinical relevance. Possible reasons are the lack of standardized methods of sampling, analysis and data processing and effects of environmental contaminants. Concentration profiles of endogenous and exogenous breath markers were determined in exhaled breath of 31 lung cancer patients, 31 smokers and 31 healthy controls by means of SPME-GC-MS. Different correcting and normalization algorithms and a principal component analysis were applied to the data. Differences of exhalation profiles in cancer and non-cancer patients did not persist if physiology and confounding variables were taken into account. Smoking history, inspired substance concentrations, age and gender were recognized as the most important confounding variables. Normalization onto PCO2 or BSA or correction for inspired concentrations only partially solved the problem. In contrast, previous smoking behaviour could be recognized unequivocally. Exhaled substance concentrations may depend on a variety of parameters other than the disease under investigation. Normalization and correcting parameters have to be chosen with care as compensating effects may be different from one substance to the other. Only well-founded biomarker identification, normalization and data processing will provide clinically relevant information from breath analysis. 2010 Elsevier B.V. All rights reserved.
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Spatial variation in attributable risks.
Congdon, Peter
2015-01-01
The attributable risk (AR) measures the contribution of a particular risk factor to a disease, and allows estimation of disease rates specific to that risk. While previous studies consider variability in ARs over demographic categories, this paper considers the extent of spatial variability in ARs estimated from multilevel data with confounders both at individual and geographic levels. A case study considers the AR for diabetes in relation to elevated BMI, and area rates for diabetes attributable to excess weight. Contextual adjustment includes known area variables, and unobserved spatially clustered influences, while spatial heterogeneity (effect modification) is considered in terms of varying effects of elevated BMI by neighbourhood deprivation category. The application is to patient register data in London, with clear evidence of spatial variation in ARs, and in small area diabetes rates attributable to excess weight. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Dipnall, Joanna F.
2016-01-01
Background Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study. Methods The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009–2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators. Results After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001). Conclusion The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin. PMID:26848571
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Dipnall, Joanna F; Pasco, Julie A; Berk, Michael; Williams, Lana J; Dodd, Seetal; Jacka, Felice N; Meyer, Denny
2016-01-01
Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study. The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009-2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators. After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001). The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin.
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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.
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Napping during the night shift and recovery after work among hospital nurses1
Palermo, Thaís Aparecida de Castro; Rotenberg, Lúcia; Zeitoune, Regina Célia Gollner; Silva-Costa, Aline; Souto, Ester Paiva; Griep, Rosane Härter
2015-01-01
OBJECTIVE: To analyze the association between the length of napping during the night shift and the recovery after work among nurses. METHOD: Cross-sectional epidemiological study involving 1940 nurses from 18 public hospitals in the City of Rio de Janeiro. A multidimensional and self-applied questionnaire was used with information about health, sociodemographic and occupational characteristics, health-related behaviors and housework. Multiple logistic regression was applied to identify the association, adjusted for confounding variables. RESULTS: The gross analyses showed 44%, 127% and 66% higher chances of a high level of recovery after work for nurses who sleep up to two hours, between 2.1 and 3 hours and 3.1 hours or more, respectively, when compared to the nurses who do not sleep. After adjusting for confounding variables, the association only continues significant for the group that sleeps 2.1 to 3 hours during the night shift (OR=1.79; 95%CI=1.33-2.41). CONCLUSION: The association between the length of napping and the high level of recovery after work, confirmed in the present results, can be included in the studies that aim to support more appropriate policies aimed at improving the workers' work, life and health conditions, not only in nursing, but night-shift workers in general. PMID:25806639
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THE EXPERIMENTAL DESIGN FOR BeO IRAADIATION EXPERIMENTS ORNL 41-8 AND ORNL 41-9
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gardiner, D.A.
1962-07-18
The experimental plan for irradiating BeO pellets in Experiments ORNL 41- 8 and ORNL 41-9 was chosen in accordance with the principles of experimental design. The design is known by statisticians as a 2/sup 5/ factorial experiment confound'' in six replications. Five variables---size, density, grain size, temperature and time--are controlled at two levels to form the basic 2i factorial experiment. The sixth variable, neutron flux, is introduced by confounding on higher-order interactions. An explanation is presented in nontechnical language the means by which the aims of the experimenters and the physical conditions affecting the experiment were utilized in constructing themore » experimental design. (auth)« less
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Beyond Free Lunch: Which Family Background Measures Matter?
ERIC Educational Resources Information Center
Lubienski, Sarah Theule; Crane, Corinna Crawford
2010-01-01
Most studies of school achievement use free-lunch eligibility or other basic indicators to adjust for differences in students' socioeconomic backgrounds. This study determines whether these variables are enough to separate the confounding effects of students' backgrounds from the main variables of interest in education studies. The Early Childhood…
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Oral contraceptive use and female genital arousal: methodological considerations.
Seal, Brooke N; Brotto, Lori A; Gorzalka, Boris B
2005-08-01
This study explored effects of oral contraceptive pill (OCP) use on physiological sexual arousal as measured by a vaginal photoplethysmograph. Sixteen women aged 18-29 viewed audiovisual neutral and erotic stimuli before and an average of 6 weeks following the onset of OCP use. Although subjective measures of sexual arousal, including perceptions of genital arousal, significantly increased in response to erotic stimuli both before and after OCP onset, physiological sexual arousal only increased before OCP use. A comparison of individual responses before and after OCP onset reveals a much higher degree of intrasubject variability after OCP onset. We discuss these findings as they relate to OCP use as a confounding methodological variable to consider in future investigations employing vaginal photoplethysmography.
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The Causal Mediation Formula - A Guide to the Assessment of Pathways and Mechanisms
2011-10-01
for estimating CDE(z) in observational studies (in the presence of unobserved confounders) can be derived using do- calculus (Pearl, 2009, pp. 85–88...2011; Albert and Nelson , 2011). 7In the presence of measured and unmeasured confounders, the general conditions under which NDE is estimable from...achieve this independence (see footnote 7), that Z may represent a vector of variables, and that integrals should replace summations when dealing with
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Measuring the surgical 'learning curve': methods, variables and competency.
Khan, Nuzhath; Abboudi, Hamid; Khan, Mohammed Shamim; Dasgupta, Prokar; Ahmed, Kamran
2014-03-01
To describe how learning curves are measured and what procedural variables are used to establish a 'learning curve' (LC). To assess whether LCs are a valuable measure of competency. A review of the surgical literature pertaining to LCs was conducted using the Medline and OVID databases. Variables should be fully defined and when possible, patient-specific variables should be used. Trainee's prior experience and level of supervision should be quantified; the case mix and complexity should ideally be constant. Logistic regression may be used to control for confounding variables. Ideally, a learning plateau should reach a predefined/expert-derived competency level, which should be fully defined. When the group splitting method is used, smaller cohorts should be used in order to narrow the range of the LC. Simulation technology and competence-based objective assessments may be used in training and assessment in LC studies. Measuring the surgical LC has potential benefits for patient safety and surgical education. However, standardisation in the methods and variables used to measure LCs is required. Confounding variables, such as participant's prior experience, case mix, difficulty of procedures and level of supervision, should be controlled. Competency and expert performance should be fully defined. © 2013 The Authors. BJU International © 2013 BJU International.
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Cloern, J.E.; Canuel, E.A.; Harris, D.
2002-01-01
We report measurements of seasonal variability in the C-N stable isotope ratios of plants collected across the habitat mosaic of San Francisco Bay, its marshes, and its tributary river system. Analyses of 868 plant samples were binned into 10 groups (e.g., terrestrial riparian, freshwater phytoplankton, salt marsh) to determine whether C-N isotopes can be used as biomarkers for tracing the origins of organic matter in this river-marsh-estuary complex. Variability of ??13C and ??15N was high (???5-10???) within each plant group, and we identified three modes of variability: (1) between species and their microhabitats, (2) over annual cycles of plant growth and senescence, and (3) between living and decomposing biomass. These modes of within-group variability obscure any source-specific isotopic signatures, confounding the application of C-N isotopes for identifying the origins of organic matter. A second confounding factor was large dissimilarity between the ??13C-??15N of primary producers and the organic-matter pools in the seston and sediments. Both confounding factors impede the application of C-N isotopes to reveal the food supply to primary consumers in ecosystems supporting diverse autotrophs and where the isotopic composition of organic matter has been transformed and become distinct from that of its parent plant sources. Our results support the advice of others: variability of C-N stable isotopes within all organic-matter pools is high and must be considered in applications of these isotopes to trace trophic linkages from primary producers to primary consumers. Isotope-based approaches are perhaps most powerful when used to complement other tools, such as molecular biomarkers, bioassays, direct measures of production, and compilations of organic-matter budgets.
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Daily commuting to work is not associated with variables of health.
Mauss, Daniel; Jarczok, Marc N; Fischer, Joachim E
2016-01-01
Commuting to work is thought to have a negative impact on employee health. We tested the association of work commute and different variables of health in German industrial employees. Self-rated variables of an industrial cohort (n = 3805; 78.9 % male) including absenteeism, presenteeism and indices reflecting stress and well-being were assessed by a questionnaire. Fasting blood samples, heart-rate variability and anthropometric data were collected. Commuting was grouped into one of four categories: 0-19.9, 20-44.9, 45-59.9, ≥60 min travelling one way to work. Bivariate associations between commuting and all variables under study were calculated. Linear regression models tested this association further, controlling for potential confounders. Commuting was positively correlated with waist circumference and inversely with triglycerides. These associations did not remain statistically significant in linear regression models controlling for age, gender, marital status, and shiftwork. No other association with variables of physical, psychological, or mental health and well-being could be found. The results indicate that commuting to work has no significant impact on well-being and health of German industrial employees.
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Siahpush, Mohammad; English, Dallas; Powles, John
2006-01-01
Objective To assess the contribution of smoking to the inverse association of mortality with years of formal education in men in Australia. Design Data were obtained from a prospective cohort study that included 17 049 men in Melbourne recruited from 1990 to 1994, most of whom were aged between 40 and 69 years at baseline. The outcome measured was all‐cause mortality. The contribution of smoking to socioeconomic status differentials was estimated by including smoking as a variable in a Cox's proportional hazards model that also included education and other potential confounding variables. Results In men, the association between education and mortality was attenuated after adjustment for smoking, and the aetiological fraction for low levels of education was reduced from 16.5% to 10.6%. Conclusions In men, smoking contributes substantially to socioeconomic differentials in mortality. Effective policies and interventions that target smoking among socially disadvantaged groups may substantially reduce socioeconomic differentials in health. PMID:17108305
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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.
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Separating decadal global water cycle variability from sea level rise.
Hamlington, B D; Reager, J T; Lo, M-H; Karnauskas, K B; Leben, R R
2017-04-20
Under a warming climate, amplification of the water cycle and changes in precipitation patterns over land are expected to occur, subsequently impacting the terrestrial water balance. On global scales, such changes in terrestrial water storage (TWS) will be reflected in the water contained in the ocean and can manifest as global sea level variations. Naturally occurring climate-driven TWS variability can temporarily obscure the long-term trend in sea level rise, in addition to modulating the impacts of sea level rise through natural periodic undulation in regional and global sea level. The internal variability of the global water cycle, therefore, confounds both the detection and attribution of sea level rise. Here, we use a suite of observations to quantify and map the contribution of TWS variability to sea level variability on decadal timescales. In particular, we find that decadal sea level variability centered in the Pacific Ocean is closely tied to low frequency variability of TWS in key areas across the globe. The unambiguous identification and clean separation of this component of variability is the missing step in uncovering the anthropogenic trend in sea level and understanding the potential for low-frequency modulation of future TWS impacts including flooding and drought.
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Gong, Jing-Bo; Wang, Ya; Lui, Simon S Y; Cheung, Eric F C; Chan, Raymond C K
2017-11-01
Childhood trauma has been shown to be a robust risk factor for mental disorders, and may exacerbate schizotypal traits or contribute to autistic trait severity. However, little is known whether childhood trauma confounds the overlap between schizotypal traits and autistic traits. This study examined whether childhood trauma acts as a confounding variable in the overlap between autistic and schizotypal traits in a large non-clinical adult sample. A total of 2469 participants completed the Autism Spectrum Quotient (AQ), the Schizotypal Personality Questionnaire (SPQ), and the Childhood Trauma Questionnaire-Short Form. Correlation analysis showed that the majority of associations between AQ variables and SPQ variables were significant (p < 0.05). In the multiple regression models predicting scores on the AQ total, scores on the three SPQ subscales were significant predictors(Ps < 0.05). Scores on the Positive schizotypy and Negative schizotypy subscales were significant predictors in the multiple regression model predicting scores on the AQ Social Skill, AQ Attention Switching, AQ Attention to Detail, AQ Communication, and AQ Imagination subscales. The association between autistic and schizotypal traits could not be explained by shared variance in terms of exposure to childhood trauma. The findings point to important overlaps in the conceptualization of ASD and SSD, independent of childhood trauma. Copyright © 2017 Elsevier B.V. All rights reserved.
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"Fundamental Causes" of Social Inequalities in Mortality: A Test of the Theory
ERIC Educational Resources Information Center
Phelan, Jo C.; Link, Bruce G.; Diez-Roux, Ana; Kawachi, Ichiro; Levin, Bruce
2004-01-01
Medicine and epidemiology currently dominate the study of the strong association between socioeconomic status and mortality. Socioeconomic status typically is viewed as a causally irrelevant "confounding variable" or as a less critical variable marking only the beginning of a causal chain in which intervening risk factors are given prominence. Yet…
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ERIC Educational Resources Information Center
Street, Nathan Lee
2017-01-01
Teacher value-added measures (VAM) are designed to provide information regarding teachers' causal impact on the academic growth of students while controlling for exogenous variables. While some researchers contend VAMs successfully and authentically measure teacher causality on learning, others suggest VAMs cannot adequately control for exogenous…
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ERIC Educational Resources Information Center
Debruine, Lisa M.; Jones, Benedict C.; Smith, Finlay G.; Little, Anthony C.
2010-01-01
Women's preferences for male masculinity are highly variable. Although many researchers explain this variability as reflecting systematic individual differences in how women resolve the tradeoff between the costs and benefits of choosing a masculine partner, others suggest that methodological differences between studies are responsible. A recent…
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Adolescent Substance Use, Sleep, and Academic Achievement: Evidence of Harm Due to Caffeine
ERIC Educational Resources Information Center
James, Jack E.; Kristjansson, Alfgeir Logi; Sigfusdottir, Inga Dora
2011-01-01
Using academic achievement as the key outcome variable, 7377 Icelandic adolescents were surveyed for cigarette smoking, alcohol use, daytime sleepiness, caffeine use, and potential confounders. Structural equation modeling (SEM) was used to examine direct and indirect effects of measured and latent variables in two models: the first with caffeine…
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Association between prolonged breast-feeding and early childhood caries: a hierarchical approach.
Nunes, Ana Margarida Melo; Alves, Claudia Maria Coelho; Borba de Araújo, Fernando; Ortiz, Tânia Mara Lopes; Ribeiro, Marizélia Rodrigues Costa; Silva, Antônio Augusto Moura da; Ribeiro, Cecília Claudia Costa
2012-12-01
This study was conducted to investigate the association between prolonged breastfeeding and early childhood caries(ECC) with adjustment for important confounders, using hieraschical approach. This retrospective cohort study involved 260 low-income children (18-42 months). The number of decayed teeth was used as a measure of caries. Following a theoretical framework, the hierarchical model was built in a forward fashion, by adding the following levels in succession: level 1: age; level 2: social variables; level 3: health variables; level 4: behavioral variables; level 5: oral hygiene-related variables; level 6: oral hygiene quality measured by visible plaque; and level 7: contamination by mutans streptococci. Sequential forward multiple Poisson regression analysis was employed. Breast-feeding was not a risk factor for ECC after adjustment for some confounders (incidence density ratio, 1.15; 95% confidence interval, 0.84-1.59, P = 0.363). Prolonged breast-feeding was not a risk factor for ECC while age, high sucrose comption between main meals and the quality of oral higiene were associated with disease in children. © 2012 John Wiley & Sons A/S.
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The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome
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
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NASA Astrophysics Data System (ADS)
Chaibub Neto, Elias
2016-11-01
Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.
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Brody, Gene H.; Lei, Man-Kit; Chae, David H.; Yu, Tianyi; Kogan, Steven M.; Beach, Steven R. H.
2013-01-01
This study was designed to examine the prospective relations of perceived racial discrimination with allostatic load (AL), along with a possible buffer of the association. A sample of 331 African Americans in the rural South provided assessments of perceived discrimination from ages 16 to 18 years. When youths were 18, caregivers reported parental emotional support, and youths assessed peer emotional support. AL and potential confounder variables were assessed when youths were 20. Latent Growth Mixture Modeling identified two perceived discrimination classes: high and stable and low and increasing. Adolescents in the high and stable class evinced heightened AL even with confounder variables controlled. The racial discrimination to AL link was not significant for young adults who received high emotional support. PMID:24673162
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The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice.
Ingvorsen, C; Karp, N A; Lelliott, C J
2017-04-10
Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes.
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Lifetime Alcohol Use & Cognitive Performance in Older Adults
Kalapatapu, Raj K.; Ventura, Maria I.; Barnes, Deborah E.
2016-01-01
Background Substance use is an important clinical issue in the older adult population. As older adults are susceptible to cognitive disorders, the intersection of the fields of substance use and cognitive neuroscience is an active area of research. Prior studies of alcohol use and cognitive performance are mixed, and inconsistencies may be due to under- or over-adjustment for confounders. Aim This manuscript adds to this literature by conducting a secondary analysis of self-reported lifetime history of alcohol use and cognitive performance in older adults (n = 133). We hypothesized that current alcohol users would have poorer cognitive performance compared to never/minimal and former alcohol users. Methods Older adult participants were classified into never/minimal alcohol users, former alcohol users, and current alcohol users. A neurocognitive battery included a global cognitive measure and individual measures of attention, memory, fluency, and executive function. A directed acyclic graph (DAG)-based approach was used to select variables to be included in the multiple linear regression models. Results Though unadjusted analyses showed some significant associations between alcohol use and cognitive performance, all associations between alcohol use and cognitive performance were eliminated after adjusting for age, education, sex, race and smoking pack years. Alcohol drink years were not significantly associated with cognitive performance among current and former alcohol users. Discussion These results suggest that lifetime alcohol use is not significantly associated with cognitive performance in older adults after adjustment for key confounders. Inconsistencies in prior studies may be due to uncontrolled confounding and/or unnecessary adjustment of mediators and/or colliders. PMID:27719514
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Tong, I S; Lu, Y
2001-01-01
To explore the best approach to identify and adjust for confounders in epidemiologic practice. In the Port Pirie cohort study, the selection of covariates was based on both a priori and an empirical consideration. In an assessment of the relationship between exposure to environmental lead and child development, change-in-estimate (CE) and significance testing (ST) criteria were compared in identifying potential confounders. The Pearson correlation coefficients were used to evaluate the potential for collinearity between pairs of major quantitative covariates. In multivariate analyses, the effects of confounding factors were assessed with multiple linear regression models. The nature and number of covariates selected varied with different confounder selection criteria and different cutoffs. Four covariates (i.e., quality of home environment, socioeconomic status (SES), maternal intelligence, and parental smoking behaviour) met the conventional CE criterion (> or =10%), whereas 14 variables met the ST criterion (p < or = 0.25). However, the magnitude of the relationship between blood lead concentration and children's IQ differed slightly after adjustment for confounding, using either the CE (partial regression coefficient: -4.4; 95% confidence interval (CI): -0.5 to -8.3) or ST criterion (-4.3; 95% CI: -0.2 to -8.4). Identification and selection of confounding factors need to be viewed cautiously in epidemiologic studies. Either the CE (e.g., > or = 10%) or ST (e.g., p < or = 0.25) criterion may be implemented in identification of a potential confounder if a study sample is sufficiently large, and both the methods are subject to arbitrariness of selecting a cut-off point. In this study, the CE criterion (i.e., > or = 10%) appears to be more stringent than the ST method (i.e., p < or = 0.25) in the identification of confounders. However, the ST rule cannot be used to determine the trueness of confounding because it cannot reflect the causal relationship between the confounder and outcome. This study shows the complexities one can expect to encounter in the identification of and adjustment for confounders.
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Jin, Huifeng; Cheng, Haojie; Chen, Wei; Sheng, Xiaoming; Levy, Mark A; Brown, Mark J; Tian, Junqiang
2018-05-01
The single nucleotide polymorphism of the gene 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. We hypothesized that variability in this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers, confounders, or both, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates. We systematically extracted from published studies the data on tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting metadata set was first used to analyze the covariates' modifying effect by meta-regression and other statistical means. Subsequently, we controlled for this modifying effect by genotype-stratifying tHcy data and analyzed the variability in the risk resulting from the confounding of covariates. The data set contains data on 36 rs1801133 covariates that were collected from 114,799 participants and 256 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification as well as confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner. We showed an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public, who increasingly receive genetic data from commercial services without interpretation of its clinical relevance. This study was registered at Research Registry with the registration number reviewregistry328.
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Staffa, Steven J; Zurakowski, David
2018-01-09
In clinical research, the gold standard level of evidence is the randomized controlled trial (RCT). The availability of nonrandomized retrospective data is growing; however, a primary concern of analyzing such data is comparability of the treatment groups with respect to confounding variables. Propensity score matching (PSM) aims to equate treatment groups with respect to measured baseline covariates to achieve a comparison with reduced selection bias. It is a valuable statistical methodology that mimics the RCT, and it may create an "apples to apples" comparison while reducing bias due to confounding. PSM can improve the quality of anesthesia research and broaden the range of research opportunities. PSM is not necessarily a magic bullet for poor-quality data, but rather may allow the researcher to achieve balanced treatment groups similar to a RCT when high-quality observational data are available. PSM may be more appealing than the common approach of including confounders in a regression model because it allows for a more intuitive analysis of a treatment effect between 2 comparable groups.We present 5 steps that anesthesiologists can use to successfully implement PSM in their research with an example from the 2015 Pediatric National Surgical Quality Improvement Program: a validated, annually updated surgery and anesthesia pediatric database. The first step of PSM is to identify its feasibility with regard to the data at hand and ensure availability of data on any potential confounders. The second step is to obtain the set of propensity scores from a logistic regression model with treatment group as the outcome and the balancing factors as predictors. The third step is to match patients in the 2 treatment groups with similar propensity scores, balancing all factors. The fourth step is to assess the success of the matching with balance diagnostics, graphically or analytically. The fifth step is to apply appropriate statistical methodology using the propensity-matched data to compare outcomes among treatment groups.PSM is becoming an increasingly more popular statistical methodology in medical research. It often allows for improved evaluation of a treatment effect that may otherwise be invalid due to a lack of balance between the 2 treatment groups with regard to confounding variables. PSM may increase the level of evidence of a study and in turn increases the strength and generalizability of its results. Our step-by-step approach provides a useful strategy for anesthesiologists to implement PSM in their future research.
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Lee, Min Kyeong; Allareddy, Veerasathpurush; Howell, T Howard; Karimbux, Nadeem Y
2011-01-01
Harvard School of Dental Medicine (HSDM) uses a hybrid problem-based approach to teaching in the predoctoral program. The objective structured clinical examination (OSCE) is a formative examination designed to assess the performance of students in the problem-based learning (PBL) curriculum. At HSDM three comprehensive examinations with OSCE components are administered during the third and fourth years of clinical training. The National Board Dental Examination (NBDE) Part II is taken in the final year of the predoctoral program. This study examines the association between the NBDE Part II and the comprehensive exams held at HSDM. Predoctoral students from the HSDM classes of 2005 and 2006 were included in this study. The outcome variable of interest was the scores obtained by students in the NBDE Part II, and the main independent variable of interest was the performance of students in the comprehensive exams (honors, pass, make-up exam to pass). The Mann-Whitney U-test was used to examine the association between the grades obtained in the each of the three comprehensive exams and the NBDE Part II scores. Multivariable linear regression analysis was also used to examine the association between the NBDE Part II scores and the comprehensive exam grades. The effect of potential confounding factors including age, sex, and race/ethnicity was adjusted. The results suggest that students who performed well in the comprehensive exams performed better on the NBDE Part II, even after adjusting for confounding factors. Future studies will examine the long-term impact of PBL on postdoctoral plans and career choices.
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NASA Technical Reports Server (NTRS)
Blomqvist, Gunnar
1989-01-01
As a starting point, the group defined a primary goal of maintaining in flight a level of systemic oxygen transport capacity comparable to each individual's preflight upright baseline. The goal of maintaining capacity at preflight levels would seem to be a reasonable objective for several different reasons, including the maintenance of good health in general and the preservation of sufficient cardiovascular reserve capacity to meet operational demands. It is also important not to introduce confounding variables in whatever other physiological studies are being performed. A change in the level of fitness is likely to be a significant confounding variable in the study of many organ systems. The principal component of the in-flight cardiovascular exercise program should be large-muscle activity such as treadmill exercise. It is desirable that at least one session per week be monitored to assure maintenance of proper functional levels and to provide guidance for any adjustments of the exercise prescription. Appropriate measurements include evaluation of the heart-rate/workload or the heart-rate/oxygen-uptake relationship. Respiratory gas analysis is helpful by providing better opportunities to document relative workload levels from analysis of the interrelationships among VO2, VCO2, and ventilation. The committee felt that there is no clear evidence that any particular in-flight exercise regimen is protective against orthostatic hypotension during the early readaptation phase. Some group members suggested that maintenance of the lower body muscle mass and muscle tone may be helpful. There is also evidence that late in-flight interventions to reexpand blood volume to preflight levels are helpful in preventing or minimizing postflight orthostatic hypotension.
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Incidence of workers compensation indemnity claims across socio-demographic and job characteristics.
Du, Juan; Leigh, J Paul
2011-10-01
We hypothesized that low socioeconomic status, employer-provided health insurance, low wages, and overtime were predictors of reporting workers compensation indemnity claims. We also tested for gender and race disparities. Responses from 17,190 (person-years) Americans participating in the Panel Study of Income Dynamics, 1997-2005, were analyzed with logistic regressions. The dependent variable indicated whether the subject collected benefits from a claim. Odds ratios for men and African-Americans were relatively large and strongly significant predictors of claims; significance for Hispanics was moderate and confounded by education. Odds ratios for variables measuring education were the largest for all statistically significant covariates. Neither low wages nor employer-provided health insurance was a consistent predictor. Due to confounding from the "not salaried" variable, overtime was not a consistently significant predictor. Few studies use nationally representative longitudinal data to consider which demographic and job characteristics predict reporting workers compensation indemnity cases. This study did and tested some common hypotheses about predictors. Copyright © 2011 Wiley-Liss, Inc.
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Doubly robust matching estimators for high dimensional confounding adjustment.
Antonelli, Joseph; Cefalu, Matthew; Palmer, Nathan; Agniel, Denis
2018-05-11
Valid estimation of treatment effects from observational data requires proper control of confounding. If the number of covariates is large relative to the number of observations, then controlling for all available covariates is infeasible. In cases where a sparsity condition holds, variable selection or penalization can reduce the dimension of the covariate space in a manner that allows for valid estimation of treatment effects. In this article, we propose matching on both the estimated propensity score and the estimated prognostic scores when the number of covariates is large relative to the number of observations. We derive asymptotic results for the matching estimator and show that it is doubly robust in the sense that only one of the two score models need be correct to obtain a consistent estimator. We show via simulation its effectiveness in controlling for confounding and highlight its potential to address nonlinear confounding. Finally, we apply the proposed procedure to analyze the effect of gender on prescription opioid use using insurance claims data. © 2018, The International Biometric Society.
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Effect decomposition in the presence of an exposure-induced mediator-outcome confounder
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
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Dialyzer Reuse with Peracetic Acid Does Not Impact Patient Mortality
Bond, T. Christopher; Krishnan, Mahesh; Wilson, Steven M.; Mayne, Tracy
2011-01-01
Summary Background and objectives Numerous studies have shown the overall benefits of dialysis filter reuse, including superior biocompatibility and decreased nonbiodegradable medical waste generation, without increased risk of mortality. A recent study reported that dialyzer reprocessing was associated with decreased patient survival; however, it did not control for sources of potential confounding. We sought to determine the effect of dialyzer reprocessing with peracetic acid on patient mortality using contemporary outcomes data and rigorous analytical techniques. Design, setting, participants, & measurements We conducted a series of analyses of hemodialysis patients examining the effects of reuse on mortality using three techniques to control for potential confounding: instrumental variables, propensity-score matching, and time-dependent survival analysis. Results In the instrumental variables analysis, patients at high reuse centers had 16.2 versus 15.9 deaths/100 patient-years in nonreuse centers. In the propensity-score matched analysis, patients with reuse had a lower death rate per 100 patient-years than those without reuse (15.2 versus 15.5). The risk ratios for the time-dependent survival analyses were 0.993 (per percent of sessions with reuse) and 0.995 (per unit of last reuse), respectively. Over the study period, 13.8 million dialyzers were saved, representing 10,000 metric tons of medical waste. Conclusions Despite the large sample size, powered to detect miniscule effects, neither the instrumental variables nor propensity-matched analyses were statistically significant. The time-dependent survival analysis showed a protective effect of reuse. These data are consistent with the preponderance of evidence showing reuse limits medical waste generation without negatively affecting clinical outcomes. PMID:21566107
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Zhang, Ling; Xue, Chengbing; Wang, Youjie; Zhang, Liuyi; Liang, Yuan
2016-01-01
Despite the benefits of maternal health services, these services are often underutilized, especially in the developing countries. The aim of the present study is to provide insight regarding factors affecting maternal health services use from the family perspective. We use data from the fourth National Health Services Survey in Jiangsu province of Eastern China to investigate the effect of family characteristics on the use of maternal health services. Family characteristics included whether or not living with parents, age of husband, husband's education, and husband's work status as well as family economic status. Demographic variables, social and environmental factors, and previous reproductive history were taken as potential confounders. Multiple logistic regression models were used to examine the independent effects of the family characteristic variables on maternal health service utilization. The data indicate that the percentages of prenatal care, postnatal visits and hospital delivery were 85.44, 65.12 and 99.59 % respectively. Living with parents was associated with less use of prenatal care and husband's age, education and employment status had no effect on the use of prenatal care after adjusting for potential confounding variables. Our findings suggest that maternal health education (especially the role of prenatal care) needs to be extended beyond the expectant mothers themselves to their parents and husbands. The difference of health care delivery as a result of traditional family culture may highlight the differences in factors influencing the use of postnatal visits and those influencing the use of prenatal care; which may be worthy of further study.
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Relative importance of climatic, geographic and socio-economic determinants of malaria in Malawi
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
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CADDIS Volume 4. Data Analysis: Basic Principles & Issues
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.
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Heart rate variability measure in breast cancer patients and survivors: A systematic review.
Arab, Claudia; Dias, Daniel Penteado Martins; Barbosa, Renata Thaís de Almeida; Carvalho, Tatiana Dias de; Valenti, Vitor Engrácia; Crocetta, Tânia Brusque; Ferreira, Marcelo; Abreu, Luiz Carlos de; Ferreira, Celso
2016-06-01
In the current study, we aimed to review literature findings showing the clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in breast cancer (BC) patients and survivors. We conducted a systematic review according to The PRISMA Statement in Medline, Scopus and Web of Science (_-2015) databases. The search was limited to articles in English language, published in peer-reviewed journals, and with adult age samples only (e.g., women, patients, or survivors, diagnosed with BC in any stage). We included observational studies and randomized trials. Detailed heart rate variability analysis (instruments, data collection protocol, and analysis methods) was required. Search terms included autonomic nervous system, heart rate variability, sympathetic and parasympathetic nervous system, autonomic dysfunction, vagal nervous and breast neoplasms, breast cancer and breast tumor. Twelve studies were included in this review. The clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in BC patients and survivors is demonstrated by association with effects of BC surgery, and treatments, and the adverse effects of surgery and treatments on survivors (e.g., cardiotoxicity, fatigue, and stress). The strength of evidence of included studies is low: small samples size and heterogeneity, presence of confounders, and observational studies design. The heart rate variability analysis could be used as a complementary non-invasive tool for the early diagnosis and better prognosis of autonomic dysfunction, and survival in BC patients. There are many potential clinical applications of heart rate variability analysis in BC patients, and the employment of such approaches could lead to lower impairment of autonomic function in this individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Temperature Variability during Delirium in ICU Patients: An Observational Study
van der Kooi, Arendina W.; Kappen, Teus H.; Raijmakers, Rosa J.; Zaal, Irene J.; Slooter, Arjen J. C.
2013-01-01
Introduction Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and –nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. Methods We included patients who experienced both delirium and delirium free days during ICU stay, based on the Confusion Assessment method for the ICU conducted by a research- physician or –nurse, in combination with inspection of medical records. We excluded patients with conditions affecting thermal regulation or therapies affecting body temperature. Daily temperature variability was determined by computing the mean absolute second derivative of the temperature signal. Temperature variability (primary outcome) and absolute body temperature (secondary outcome) were compared between delirium- and non-delirium days with a linear mixed model and adjusted for daily mean Richmond Agitation and Sedation Scale scores and daily maximum Sequential Organ Failure Assessment scores. Results Temperature variability was increased during delirium-days compared to days without delirium (βunadjusted=0.007, 95% confidence interval (CI)=0.004 to 0.011, p<0.001). Adjustment for confounders did not alter this result (βadjusted=0.005, 95% CI=0.002 to 0.008, p<0.001). Delirium was not associated with absolute body temperature (βunadjusted=-0.03, 95% CI=-0.17 to 0.10, p=0.61). This did not change after adjusting for confounders (βadjusted=-0.03, 95% CI=-0.17 to 0.10, p=0.63). Conclusions Our study suggests that temperature variability is increased during ICU delirium. PMID:24194955
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Clustering Words to Match Conditions: An Algorithm for Stimuli Selection in Factorial Designs
ERIC Educational Resources Information Center
Guasch, Marc; Haro, Juan; Boada, Roger
2017-01-01
With the increasing refinement of language processing models and the new discoveries about which variables can modulate these processes, stimuli selection for experiments with a factorial design is becoming a tough task. Selecting sets of words that differ in one variable, while matching these same words into dozens of other confounding variables…
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Is protective equipment useful in preventing concussion? A systematic review of the literature.
Benson, B W; Hamilton, G M; Meeuwisse, W H; McCrory, P; Dvorak, J
2009-05-01
To determine if there is evidence that equipment use reduces sport concussion risk and/or severity. 12 electronic databases were searched using a combination of Medical Subject Headings and text words to identify relevant articles. Specific inclusion and exclusion criteria were used to select studies for review. Data extracted included design, study population, exposure/outcome measures and results. The quality of evidence was assessed based on epidemiologic criteria regarding internal and external validity (ie, strength of design, sample size/power calculation, selection bias, misclassification bias, control of potential confounding and effect modification). In total, 51 studies were selected for review. A comparison between studies was difficult due to the variability in research designs, definition of concussion, mouthguard/helmet/headgear/face shield types, measurements used to assess exposure and outcomes, and variety of sports assessed. The majority of studies were observational, with 23 analytical epidemiologic designs related to the subject area. Selection bias was a concern in the reviewed studies, as was the lack of measurement and control for potentially confounding variables. There is evidence that helmet use reduces head injury risk in skiing, snowboarding and bicycling, but the effect on concussion risk is inconclusive. No strong evidence exists for the use of mouthguards or face shields to reduce concussion risk. Evidence is provided to suggest that full facial protection in ice hockey may reduce concussion severity, as measured by time loss from competition.
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Eaton, Jennifer L; Zhang, Xingqi; Barnes, Randall B
2014-11-01
To compare live birth rates following ultrasound-guided embryo transfer (ET) by reproductive endocrinology and infertility fellows versus attending physicians. Women who underwent their first day-3, fresh, nondonor ET between Oct. 1, 2005, and April 1, 2011, at our academic center were included in this retrospective cohort study. Embryos were designated high quality if they had 8 cells, less than 10% fragmentation, and no asymmetry. ET was performed with the afterload technique under ultrasound guidance. Categorical variables were evaluated with the χ(2) test and continuous variables with the Student t test. Logistic regression was performed to assess the relationship between ET physician and live birth rate while adjusting for potential confounders. Seven hundred sixty women underwent ET by an attending physician, and 104 by a fellow. Baseline characteristics were similar between the groups. The live birth rate was 31% following ET by an attending physician, compared with 34% following ET by a fellow (P = .65). Logistic regression adjusting for potential confounders demonstrated no significant association between ET physician and live birth rate. This retrospective study demonstrated no significant difference in live birth rates following ultrasound-guided ET by fellows vs attending physicians at our institution. These data suggest that academic practices using the afterload method and ultrasound guidance can train fellows to perform ET without compromising success rates. Copyright © 2014 Elsevier Inc. All rights reserved.
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Plasma 17-alpha-OH-progesterone in female workers exposed to urban pollutants.
Ciarrocca, M; Cerratti, D; Capozzella, A; Rosati, M V; Anzani, M F; Bernardini, A; Casale, T; Pimpinella, B; Tomei, G; Monti, C; Tomao, E; Tomei, F
2006-01-01
The aim of this study is to evaluate whether occupational exposure to urban pollutants could cause alteration in plasma 17-alpha-OH-P levels in female workers. After excluding the subjects with the principal confounding factors, traffic police and controls were matched by age, working life, age of menarche, menstrual cycle day, BMI, drinking habits, habitual consumption of soy and Italian coffee. 68 traffic police and 82 controls (7th day; follicular phase of the ovarian cycle), 37 traffic police and 20 controls (21st day; lutheal phase of the ovarian cycle) were included in the study and matched for the above mentioned variables. In follicular and lutheal phase of ovarian cycle, 17-alpha-OH-P mean levels and the distribution of 17-alpha-OH-P values were significantly higher in traffic police vs. controls. A higher instance of mental health disorders in traffic police vs. controls was found, although the difference was not significant. Considering that the potential confounding effect of extraneous factors was controlled by restricting the study population and by matching traffic police vs. controls on the above mentioned variables, our results suggest that occupational exposure to urban pollutants may alter plasma 17-alpha-OH-P concentrations. 17-alpha-OH-P could be used in an occupational setting as an early biomarker of exposure to urban pollutants, valuable for a group, even before the onset of related pathologies.
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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
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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.
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Belleudi, Valeria; Trotta, Francesco; Vecchi, Simona; Amato, Laura; Addis, Antonio; Davoli, Marina
2018-05-16
Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. To conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. We searched PubMed, EMBASE, and Web of Science (updated 1/31/2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly, previous drug use and switching reasons were considered. All findings were summarized in descriptive analyses. Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular and rheumatology were the most frequently represented clinical areas. 75% of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes were measured to identify switching connected with lack of effectiveness or adverse events. This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs. Copyright © 2018. Published by Elsevier Inc.
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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.
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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.
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Gardening and age-related weight gain: Results from a cross-sectional survey of Denver residents.
Litt, Jill S; Lambert, Jeffrey Richard; Glueck, Deborah H
2017-12-01
This study examined whether gardening modifies the association between age and body mass index (BMI). We used data from the Neighborhood Environments and Health Survey, which was conducted in Denver (N = 469) between 2006 and 2007. We fit two general linear mixed models. The base model had BMI in kg/m 2 as the outcome, and age, an indicator variable for non-gardening status and the age-by-non-gardening status interaction as predictors. The adjusted model included as covariates the potential confounders of education, ethnicity and self-reported health. We assessed self-selection bias and confounding. BMI was 27.18 kg/m 2 for non-gardeners, 25.62 kg/m 2 for home gardeners, and 24.17 kg/m 2 for community gardeners. In the base model, a statistically significant association was observed between age and BMI for non-gardeners but not for the combined community and home gardening group (F = 9.27, ndf = 1, ddf = 441, p = 0.0025). In the adjusted model, the association between age and BMI in non-gardeners was not statistically significant (F = 1.72, ndf = 1, ddf = 431, p = 0.1908). Gardeners differed on social and demographic factors when compared to non-gardeners. The results from the base model are consistent with the hypothesis that gardening might offset age-related weight gain. However, the cross-sectional design does not permit differentiation of true causal effects from the possible effects of bias and confounding. As a follow-up study, to remove bias and confounding, we are conducting a randomized clinical trial of community gardening in Denver.
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Jou, Jerwen
2014-10-01
Subjects performed Sternberg-type memory recognition tasks (Sternberg paradigm) in four experiments. Category-instance names were used as learning and testing materials. Sternberg's original experiments demonstrated a linear relation between reaction time (RT) and memory-set size (MSS). A few later studies found no relation, and other studies found a nonlinear relation (logarithmic) between the two variables. These deviations were used as evidence undermining Sternberg's serial scan theory. This study identified two confounding variables in the fixed-set procedure of the paradigm (where multiple probes are presented at test for a learned memory set) that could generate a MSS RT function that was either flat or logarithmic rather than linearly increasing. These two confounding variables were task-switching cost and repetition priming. The former factor worked against smaller memory sets and in favour of larger sets whereas the latter factor worked in the opposite way. Results demonstrated that a null or a logarithmic RT-to-MSS relation could be the artefact of the combined effects of these two variables. The Sternberg paradigm has been used widely in memory research, and a thorough understanding of the subtle methodological pitfalls is crucial. It is suggested that a varied-set procedure (where only one probe is presented at test for a learned memory set) is a more contamination-free procedure for measuring the MSS effects, and that if a fixed-set procedure is used, it is worthwhile examining the RT function of the very first trials across the MSSs, which are presumably relatively free of contamination by the subsequent trials.
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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.
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Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.
Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R
2016-06-01
In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.
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Rudolph, Kara E.; Sánchez, Brisa N.; Stuart, Elizabeth A.; Greenberg, Benjamin; Fujishiro, Kaori; Wand, Gary S.; Shrager, Sandi; Seeman, Teresa; Diez Roux, Ana V.; Golden, Sherita H.
2016-01-01
Evidence of the link between job strain and cortisol levels has been inconsistent. This could be due to failure to account for cortisol variability leading to underestimated standard errors. Our objective was to model the relationship between job strain and the whole cortisol curve, accounting for sources of cortisol variability. Our functional mixed-model approach incorporated all available data—18 samples over 3 days—and uncertainty in estimated relationships. We used employed participants from the Multi-Ethnic Study of Atherosclerosis Stress I Study and data collected between 2002 and 2006. We used propensity score matching on an extensive set of variables to control for sources of confounding. We found that job strain was associated with lower salivary cortisol levels and lower total area under the curve. We found no relationship between job strain and the cortisol awakening response. Our findings differed from those of several previous studies. It is plausible that our results were unique to middle- to older-aged racially, ethnically, and occupationally diverse adults and were therefore not inconsistent with previous research among younger, mostly white samples. However, it is also plausible that previous findings were influenced by residual confounding and failure to propagate uncertainty (i.e., account for the multiple sources of variability) in estimating cortisol features. PMID:26905339
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Dai, James Y.; Chan, Kwun Chuen Gary; Hsu, Li
2014-01-01
Instrumental variable regression is one way to overcome unmeasured confounding and estimate causal effect in observational studies. Built on structural mean models, there has been considerale work recently developed for consistent estimation of causal relative risk and causal odds ratio. Such models can sometimes suffer from identification issues for weak instruments. This hampered the applicability of Mendelian randomization analysis in genetic epidemiology. When there are multiple genetic variants available as instrumental variables, and causal effect is defined in a generalized linear model in the presence of unmeasured confounders, we propose to test concordance between instrumental variable effects on the intermediate exposure and instrumental variable effects on the disease outcome, as a means to test the causal effect. We show that a class of generalized least squares estimators provide valid and consistent tests of causality. For causal effect of a continuous exposure on a dichotomous outcome in logistic models, the proposed estimators are shown to be asymptotically conservative. When the disease outcome is rare, such estimators are consistent due to the log-linear approximation of the logistic function. Optimality of such estimators relative to the well-known two-stage least squares estimator and the double-logistic structural mean model is further discussed. PMID:24863158
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The individualistic fallacy, ecological studies and instrumental variables: a causal interpretation.
Loney, Tom; Nagelkerke, Nico J
2014-01-01
The validity of ecological studies in epidemiology for inferring causal relationships has been widely challenged as observed associations could be biased by the Ecological Fallacy. We reconsider the important design components of ecological studies, and discuss the conditions that may lead to spurious associations. Ecological associations are useful and valid when the ecological exposures can be interpreted as Instrumental Variables. A suitable example may be a time series analysis of environmental pollution (e.g. particulate matter with an aerodynamic diameter of <10 micrometres; PM10) and health outcomes (e.g. hospital admissions for acute myocardial infarction) as environmental pollution levels are a cause of individual exposure levels and not just an aggregate measurement. Ecological exposures may also be employed in situations (perhaps rare) where individual exposures are known but their associations with health outcomes are confounded by unknown or unquantifiable factors. Ecological associations have a notorious reputation in epidemiology and individualistic associations are considered superior to ecological associations because of the "ecological fallacy". We have argued that this is incorrect in situations in which ecological or aggregate exposures can serve as an instrumental variable and associations between individual exposure and outcome are likely to be confounded by unmeasured variables.
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2010-06-01
without influences that may confound the re- sults (e.g., pain, anxiety , transport conditions, caregiver in- terventions). Second, rather than being...32. Ryan KL, Rickards CA, Muniz GW, Moralez G, Convertino VA: Interindi- vidual variability in heart rate variability ( HRV ) and complexity measure...Raimondi G, Legramante JM, Macerata A: Revisiting the potential of time-domain indexes in short-term HRV analysis. Biomed Tech (Berl) 51:190Y193, 2006
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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.
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A cohort study of psychosocial work stressors on work ability among Brazilian hospital workers.
Martinez, Maria Carmen; do Rosário Dias de Oliveira Latorre, Maria; Fischer, Frida Marina
2015-07-01
Hospital work is characterized by stressors that can influence work ability. The present study aims to assess the association between psychosocial work stressors and changes in work ability in a group of Brazilian hospital employees. From 1,022 workers included in a 3-year cohort started in 2009, 423 (41.4%) returned the applied questionnaires in 2012. Changes in work ability were considered as the dependent variable and the investigated psychosocial work stressors as independent variables. Logistic regression models adjusted for potential con-founders (demographic, occupational features, social support, overcommitment, and situations liable to cause pain/injury). High levels of exposure to psychosocial work stressors were significantly associated with decreased work ability: job strain (OR = 2.81), effort-reward imbalance (OR = 3.21). Strategies to reduce psychosocial work stressors should be considered to maintain hospital employees' work ability. Such strategies have implications for institutional and social policies and might be included in quality management programs. © 2015 Wiley Periodicals, Inc.
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Breast milk and cognitive development—the role of confounders: a systematic review
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
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Forecasting high-priority infectious disease surveillance regions: a socioeconomic model.
Chan, Emily H; Scales, David A; Brewer, Timothy F; Madoff, Lawrence C; Pollack, Marjorie P; Hoen, Anne G; Choden, Tenzin; Brownstein, John S
2013-02-01
Few researchers have assessed the relationships between socioeconomic inequality and infectious disease outbreaks at the population level globally. We use a socioeconomic model to forecast national annual rates of infectious disease outbreaks. We constructed a multivariate mixed-effects Poisson model of the number of times a given country was the origin of an outbreak in a given year. The dataset included 389 outbreaks of international concern reported in the World Health Organization's Disease Outbreak News from 1996 to 2008. The initial full model included 9 socioeconomic variables related to education, poverty, population health, urbanization, health infrastructure, gender equality, communication, transportation, and democracy, and 1 composite index. Population, latitude, and elevation were included as potential confounders. The initial model was pared down to a final model by a backwards elimination procedure. The dependent and independent variables were lagged by 2 years to allow for forecasting future rates. Among the socioeconomic variables tested, the final model included child measles immunization rate and telephone line density. The Democratic Republic of Congo, China, and Brazil were predicted to be at the highest risk for outbreaks in 2010, and Colombia and Indonesia were predicted to have the highest percentage of increase in their risk compared to their average over 1996-2008. Understanding socioeconomic factors could help improve the understanding of outbreak risk. The inclusion of the measles immunization variable suggests that there is a fundamental basis in ensuring adequate public health capacity. Increased vigilance and expanding public health capacity should be prioritized in the projected high-risk regions.
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Sheikh, Mashhood Ahmed
2017-01-01
The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant ( p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation.
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Sheikh, Mashhood Ahmed
2017-01-01
The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant (p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation. PMID:28824498
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Weiss, Noel S; Dhillon, Preet K; Etzioni, Ruth
2004-07-01
A case-control study of the efficacy of cancer screening, like any other case-control study, must deal with potential confounding. There are 2 categories of confounding variables that pose special problems for studies of screening: (1) age and calendar time resulting from different temporal distributions of screening between cases and controls irrespective of whether the screening test leads to a reduction in mortality; and (2) the administration of other screening tests for the cancer in question when it is not clear whether the result of the other test had a bearing on the decision to order the test under study. We describe circumstances in which confounding from these sources can be dealt with satisfactorily by means of restriction or adjustment, and other circumstances in which it cannot. Copyright 2004 Lippincott Williams and Wilkins
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Simpson's paradox: A statistician's case study.
Chu, Kevin H; Brown, Nathan J; Pelecanos, Anita; Brown, Anthony Ft
2018-02-26
Gender equality and workforce diversity has recently been in the forefront of College discussions. Reasons for the difference between various groups may not be as they initially appeared. The results of comparing the outcome between two groups can sometimes be confounded and even reversed by an unrecognised third variable. This concept is known as Simpson's Paradox, and is illustrated here using a renowned case study on potential gender bias for acceptance to Graduate School at the University of California, Berkeley. The investigation showed that males were 1.8 times more likely to be admitted to Graduate School than females in 1973. Initially it appeared that women were discriminated against in the selection process. However, when admissions were re-examined at individual Departments of the School, admission tended to be better for women than men in four of six Departments. This contradiction or paradox tells us that the association between admission and gender was dependent upon on Department. The confounding effect of Department was defined by two characteristics. Firstly, a strong association between Department and admission: some Departments admitted much smaller percentages of applicants than others. Secondly, a strong association between Department and gender: females tended to apply to Departments with lower admission rates. The explanation of differences between groups can be multifactorial. A search for possible confounders will assist in this understanding. This could apply whenever two groups initially appear to differ, but on closer analysis this difference is either unfounded, or even reversed by reference to a third, confounding variable. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.
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Clemens, Tom
2017-01-01
Abstract Background: Patterns of adverse birth outcomes vary spatially and there is evidence that this may relate to features of the physical environment such as air pollution. However, other social characteristics of the environment such as levels of crime are relatively understudied. This study examines the association between crime rates and birth weight and prematurity. Methods: Maternity inpatient data recorded at birth, including residential postcode, was linked to a representative 5% sample of Scottish Census data and small area crime rates from Scottish Police forces. Coefficients associated with crime were reported from crude and confounder adjusted models predicting low birth weight (< 2500 g), mean birthweight, small for gestational age and prematurity for all singleton live births. Results: Total crime rates were associated with strong and significant reductions in mean birth weight and increases in the risks of both a small for gestational age baby and premature birth. These effects, with the exception of prematurity, were robust to adjustment for individual characteristics including smoking, ethnicity and other socio-economic variables as well as area based confounders including air pollution. Mean birth weight was robust to additional adjustment for neighbourhood income deprivation. Conclusion: The level of crime in a mother’s area of residence, which may be a proxy for the degree of threat felt and therefore stress experienced, appears to be an important determinant of the risk of adverse birth outcomes. PMID:27578830
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Flawed gun policy research could endanger public safety.
Webster, D W; Vernick, J S; Ludwig, J; Lester, K J
1997-01-01
A highly publicized recent study by Lott and Mustard concludes that laws easing restrictions on licenses for carrying concealed firearms in public substantially reduce violent crime. Several serious flaws in the study render the authors' conclusions insupportable. These flaws include misclassification of gun-carrying laws, endogeneity of predictor variables, omission of confounding variables, and failure to control for the cyclical nature of crime trends. Most of these problems should bias results toward overestimating the crime-reducing effects of laws making it easier to carry concealed firearms in public. Lott and Mustard's statistical models produce findings inconsistent with criminological theories and well-established facts about crime, and subsequent reanalysis of their data challenges their conclusions. Public health professionals should understand the methodological issues raised in this commentary, particularly when flawed research could influence the introduction of policies with potentially deleterious consequences. PMID:9224169
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Gibbs, Jenna C; Giangregorio, Lora M; Wong, Andy K O; Josse, Robert G; Cheung, Angela M
2017-10-01
The purpose of this cross-sectional study was to determine how appendicular lean mass index (ALMI), and whole body lean (LMI) and fat mass indices (FMI) associate with estimated bone strength outcomes at the distal radius and tibia in adults aged 40 years and older. Dual energy X-ray absorptiometry (DXA) scans were performed to determine body composition, including whole body lean and fat mass, and appendicular lean mass. ALMI (appendicular lean mass/height 2 ), LMI (lean tissue mass/height 2 ) and FMI (fat mass/height 2 ) were calculated. High-resolution peripheral quantitative computed tomography (HRpQCT) scans were performed to assess bone structural properties at the distal radius and tibia. Using finite element analysis, failure load (N), stiffness (N/mm), ultimate stress (MPa), and cortical-to-trabecular load ratio were estimated from HRpQCT scans. The associations between body composition (ALMI, LMI, FMI) and estimated bone strength were examined using bivariate and multivariable linear regression analyses adjusting for age, sex, and other confounding variables. In 197 participants (127 women; mean±SD, age: 69.5±10.3y, body mass index: 27.95±4.95kg/m 2 , ALMI: 7.31±1.31kg/m 2 ), ALMI and LMI were significantly associated with failure load at the distal radius and tibia (explained 39%-48% of the variance) and remained significant after adjusting for confounding variables and multiple testing (R 2 =0.586-0.645, p<0.001). ALMI, LMI, and FMI did not have significant associations with ultimate stress in our multivariable models. FMI was significantly associated with cortical-to-trabecular load ratio at the distal radius and tibia (explained 6%-12% of the variance) and remained significant after adjusting for confounders and multiple testing (R 2 =0.208-0.243, p<0.001). FMI was no longer significantly associated with failure load after adjusting for confounders. These findings suggest that ALMI and LMI are important determinants of estimated bone strength, particularly failure load, at the distal radius and tibia, and may contribute to preservation of bone strength in middle-to-late adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.
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Causal inference, probability theory, and graphical insights.
Baker, Stuart G
2013-11-10
Causal inference from observational studies is a fundamental topic in biostatistics. The causal graph literature typically views probability theory as insufficient to express causal concepts in observational studies. In contrast, the view here is that probability theory is a desirable and sufficient basis for many topics in causal inference for the following two reasons. First, probability theory is generally more flexible than causal graphs: Besides explaining such causal graph topics as M-bias (adjusting for a collider) and bias amplification and attenuation (when adjusting for instrumental variable), probability theory is also the foundation of the paired availability design for historical controls, which does not fit into a causal graph framework. Second, probability theory is the basis for insightful graphical displays including the BK-Plot for understanding Simpson's paradox with a binary confounder, the BK2-Plot for understanding bias amplification and attenuation in the presence of an unobserved binary confounder, and the PAD-Plot for understanding the principal stratification component of the paired availability design. Published 2013. This article is a US Government work and is in the public domain in the USA.
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Self-reported Vitamin Supplementation in Early Pregnancy and Risk of Miscarriage
Olshan, Andrew F.; Herring, Amy H.; Savitz, David A.; Siega-Riz, Anna Maria; Hartmann, Katherine E.
2009-01-01
Miscarriage is a common and poorly understood adverse pregnancy outcome. In this study, the authors sought to evaluate the relation between self-reported use of prenatal vitamins in early pregnancy and the risk of miscarriage. Between 2000 and 2008, 4,752 US women were prospectively enrolled in Right From the Start. Information about vitamin use was obtained from a first-trimester interview. Discrete-time hazard models were used, candidate confounders were assessed, and the following variables were included in the model: study site, maternal age, gravidity, marital status, education, race/ethnicity, smoking, and use of progesterone in early pregnancy. Approximately 95% of participants reported use of vitamins during early pregnancy. A total of 524 women had a miscarriage. In the final adjusted model, any use of vitamins during pregnancy was associated with decreased odds of miscarriage (odds ratio = 0.43, 95% confidence interval: 0.30, 0.60) in comparison with no exposure. These results should be viewed in the context of a potentially preventive biologic mechanism mitigated by possible confounding by healthy behaviors and practices that are also associated with vitamin supplement use during pregnancy. PMID:19372214
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Self-reported vitamin supplementation in early pregnancy and risk of miscarriage.
Hasan, Reem; Olshan, Andrew F; Herring, Amy H; Savitz, David A; Siega-Riz, Anna Maria; Hartmann, Katherine E
2009-06-01
Miscarriage is a common and poorly understood adverse pregnancy outcome. In this study, the authors sought to evaluate the relation between self-reported use of prenatal vitamins in early pregnancy and the risk of miscarriage. Between 2000 and 2008, 4,752 US women were prospectively enrolled in Right From the Start. Information about vitamin use was obtained from a first-trimester interview. Discrete-time hazard models were used, candidate confounders were assessed, and the following variables were included in the model: study site, maternal age, gravidity, marital status, education, race/ethnicity, smoking, and use of progesterone in early pregnancy. Approximately 95% of participants reported use of vitamins during early pregnancy. A total of 524 women had a miscarriage. In the final adjusted model, any use of vitamins during pregnancy was associated with decreased odds of miscarriage (odds ratio = 0.43, 95% confidence interval: 0.30, 0.60) in comparison with no exposure. These results should be viewed in the context of a potentially preventive biologic mechanism mitigated by possible confounding by healthy behaviors and practices that are also associated with vitamin supplement use during pregnancy.
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Ultrasonic Power Output Measurement by Pulsed Radiation Pressure
Fick, Steven E.; Breckenridge, Franklin R.
1996-01-01
Direct measurements of time-averaged spatially integrated output power radiated into reflectionless water loads can be made with high accuracy using techniques which exploit the radiation pressure exerted by sound on all objects in its path. With an absorptive target arranged to intercept the entirety of an ultrasound beam, total beam power can be determined as accurately as the radiation force induced on the target can be measured in isolation from confounding forces due to buoyancy, streaming, surface tension, and vibration. Pulse modulation of the incident ultrasound at a frequency well above those characteristics of confounding phenomena provides the desired isolation and other significant advantages in the operation of the radiation force balance (RFB) constructed in 1974. Equipped with purpose-built transducers and electronics, the RFB is adjusted to equate the radiation force and a counterforce generated by an actuator calibrated against reference masses using direct current as the transfer variable. Improvements made during its one overhaul in 1988 have nearly halved its overall measurement uncertainty and extended the capabilities of the RFB to include measuring the output of ultrasonic systems with arbitrary pulse waveforms. PMID:27805084
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Estimating Causal Effects with Ancestral Graph Markov Models
Malinsky, Daniel; Spirtes, Peter
2017-01-01
We present an algorithm for estimating bounds on causal effects from observational data which combines graphical model search with simple linear regression. We assume that the underlying system can be represented by a linear structural equation model with no feedback, and we allow for the possibility of latent variables. Under assumptions standard in the causal search literature, we use conditional independence constraints to search for an equivalence class of ancestral graphs. Then, for each model in the equivalence class, we perform the appropriate regression (using causal structure information to determine which covariates to include in the regression) to estimate a set of possible causal effects. Our approach is based on the “IDA” procedure of Maathuis et al. (2009), which assumes that all relevant variables have been measured (i.e., no unmeasured confounders). We generalize their work by relaxing this assumption, which is often violated in applied contexts. We validate the performance of our algorithm on simulated data and demonstrate improved precision over IDA when latent variables are present. PMID:28217244
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Packet Randomized Experiments for Eliminating Classes of Confounders
Pavela, Greg; Wiener, Howard; Fontaine, Kevin R.; Fields, David A.; Voss, Jameson D.; Allison, David B.
2014-01-01
Background Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design—packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. Methods We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. Results PREs have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. Conclusions Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables. PMID:25444088
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Echocardiographic nomograms for chamber diameters and areas in Caucasian children.
Cantinotti, Massimiliano; Scalese, Marco; Murzi, Bruno; Assanta, Nadia; Spadoni, Isabella; De Lucia, Vittoria; Crocetti, Maura; Cresti, Alberto; Gallotta, Milena; Marotta, Marco; Tyack, Karin; Molinaro, Sabrina; Iervasi, Giorgio
2014-12-01
Although a quantitative evaluation of cardiac chamber dimensions in pediatric echocardiography is often important, nomograms for these structures are limited. The aim of this study was to establish reliable echocardiographic nomograms of cardiac chamber diameters and areas in a wide population of children. A total of 1,091 Caucasian Italian healthy children (age range, 0 days to 17 years; 44.8% female) with body surface areas (BSAs) ranging from 0.12 to 1.8 m(2) were prospectively enrolled. Twenty-two two-dimensional and M-mode measurements of atrial and ventricular chamber diameters and areas were performed. Models using linear, logarithmic, exponential, and square-root relationships were tested. Heteroscedasticity was tested by the White test and the Breusch-Pagan test. Age, weight, height, and BSA, calculated by the Haycock formula, were used as the independent variables in different analyses to predict the mean value of each echocardiographic measurement. The influence of various confounders, including gender, type of delivery, prematurity, and interobserver variability, was also evaluated. Structured Z scores were then computed. The Haycock formula provided the best fit and was used when presenting data as predicted values (mean ± 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. Confounders were not included in the final models, because they did not show significant effects for most of the measurements. Echocardiographic reference values are presented for chamber area and diameters, derived from a large population of healthy children. These data partly cover a gap in actual pediatric echocardiographic nomograms. Further studies are required to reinforce these data, as well as to evaluate other parameters and ethnicities. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
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Factors associated with dropout in medical education: a literature review.
O'Neill, Lotte Dyhrberg; Wallstedt, Birgitta; Eika, Berit; Hartvigsen, Jan
2011-05-01
Medical school dropout may have negative consequences for society, patients, the profession, schools and dropouts. To our knowledge, the literature dealing with dropout from medical school has never been systematically and critically appraised. This review aimed to systematically and critically review studies dealing with factors found to be associated with dropping out of medical school. A systematic critical literature review of the international peer-reviewed research literature on medical education was performed. A primary search was conducted and subsequently supplemented with ancestry and descendancy searches. The population of interest was medical students and the outcome was dropout. Abstract/title screening and quality assessment were performed by two independent researchers. Studies were assessed on six domains of quality: study participation; study attrition; predictor measurement; measurement of and accounting for confounders; outcome measurement, and analysis. Only studies that accounted for confounding were included in the final analysis. Of 625 studies found, 48 were quality-assessed and 13 of these were eventually included based on their fulfilment of our quality-related criteria. A range of entry qualifications seemed to be associated with greater chances of a student dropping out (odds ratio [OR] = 1.65-4.00). Struggling academically in medical school may be strongly associated with dropout. By contrast, no specific pattern of demographic variables was particularly important in relation to dropout. The effects of socio-economic, psychological and educational variables on dropout were not well investigated. More research into causal models and theory testing, which considers the effects of education, organisation and institution, is necessary if we are to learn more about how we can actively prevent medical student withdrawal. © Blackwell Publishing Ltd 2011.
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Empowerment of women and its association with the health of the community.
Varkey, Prathibha; Mbbs; Kureshi, Sarah; Lesnick, Timothy
2010-01-01
Empowerment and opportunities to experience power and control in one's life contribute to health and wellness. Although studies have assessed specific factors related to women's empowerment and their influence on health outcomes, there is a dearth of published literature assessing the relationship of the empowerment of women with the overall health of a community. By means of this article, we aim to assess the relationship of women's empowerment with health in 75 countries. We used the gender empowerment measure (GEM), a composite index measuring gender inequality in economic participation and decision making, political participation and decision making, and power over economic resources. All 75 countries with GEM values in the 2006 Human Development Report (HDR) were included in the study. Association between the GEM values and seven health indicators was evaluated using descriptive statistics, scatter plots, and simple and multiple linear regression models. We also controlled for gross domestic product (GDP) as a possible confounding factor and included this variable in the multiple regression models. When GDP was not considered, GEM had a statistically significant association with all health indicator variables except for proportion of 1-year-olds immunized against measles (correlation coefficient 0.063, p = 0.597). After adjusting for GDP, GEM was significantly associated with low birth weight, fertility rate, infant mortality, and age
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Experimental Design in Clinical 'Omics Biomarker Discovery.
Forshed, Jenny
2017-11-03
This tutorial highlights some issues in the experimental design of clinical 'omics biomarker discovery, how to avoid bias and get as true quantities as possible from biochemical analyses, and how to select samples to improve the chance of answering the clinical question at issue. This includes the importance of defining clinical aim and end point, knowing the variability in the results, randomization of samples, sample size, statistical power, and how to avoid confounding factors by including clinical data in the sample selection, that is, how to avoid unpleasant surprises at the point of statistical analysis. The aim of this Tutorial is to help translational clinical and preclinical biomarker candidate research and to improve the validity and potential of future biomarker candidate findings.
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Factors that encourage females to pursue physical science careers: Testing five common hypotheses
NASA Astrophysics Data System (ADS)
Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sadler, Philip M.; Sonnert, Gerhard
2012-03-01
There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using Propensity Score Matching (PSM) on national data (n=7505) drawn from the Persistence Research in Science and Engineering (PRiSE) project, we test five commonly held beliefs including having a single-sex physics class, having a female physics teacher, having female scientist guest speakers in physics class, discussing the work of women scientists in physics class, and discussing the under-representation of women in physics class. The effect of these experiences is compared for female students who are matched on several factors, including parental education, prior science/math interests, and academic background, thereby controlling for the effect of many confounding variables.
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Does extending health insurance coverage to the uninsured improve population health outcomes?
Thornton, James A; Rice, Jennifer L
2008-01-01
An ongoing debate exists about whether the US should adopt a universal health insurance programme. Much of the debate has focused on programme implementation and cost, with relatively little attention to benefits for social welfare. To estimate the effect on US population health outcomes, measured by mortality, of extending private health insurance to the uninsured, and to obtain a rough estimate of the aggregate economic benefits of extending insurance coverage to the uninsured. We use state-level panel data for all 50 states for the period 1990-2000 to estimate a health insurance augmented, aggregate health production function for the US. An instrumental variables fixed-effects estimator is used to account for confounding variables and reverse causation from health status to insurance coverage. Several observed factors, such as income, education, unemployment, cigarette and alcohol consumption and population demographic characteristics are included to control for potential confounding variables that vary across both states and time. The results indicate a negative relationship between private insurance and mortality, thus suggesting that extending insurance to the uninsured population would result in an improvement in population health outcomes. The estimate of the marginal effect of insurance coverage indicates that a 10% increase in the population-insured rate of a state reduces mortality by 1.69-1.92%. Using data for the year 2003, we calculate that extending private insurance coverage to the entire uninsured population in the US would save over 75 000 lives annually and may yield annual net benefits to the nation in excess of $US400 billion. This analysis suggests that extending health insurance coverage through the private market to the 46 million Americans without health insurance may well produce large social economic benefits for the nation as a whole.
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Colle, Romain; Segawa, Tomoyuki; Chupin, Marie; Tran Dong, Minh Ngoc Thien Kim; Hardy, Patrick; Falissard, Bruno; Colliot, Olivier; Ducreux, Denis; Corruble, Emmanuelle
2017-02-15
Three studies assessed the association of early life adversity (ELA) and hippocampal volumes in depressed patients, of which one was negative and the two others did not control for several potential confounding variables. Since the association of ELA and hippocampal volumes differ in male and female healthy volunteers, we investigated the association of ELA and hippocampal volumes in depressed patients, while focusing specifically on sex and controlling for several relevant socio-demographic and clinical variables. Sixty-three depressed in-patients treated in a psychiatric setting, with a current Major Depressive Episode (MDE) and a Major Depressive Disorder (MDD) were included and assessed for ELA. Hippocampal volumes were measured with brain magnetic resonance imaging (MRI) and automatic segmentation. They were compared between patients with (n = 28) or without (n = 35) ELA. After bivariate analyses, multivariate regression analyses tested the interaction of sex and ELA on hippocampal volume and were adjusted for several potential confounding variables. The subgroups of men (n = 26) and women (n = 37) were assessed separately. Patients with ELA had a smaller hippocampus than those without ELA (4.65 (±1.11) cm 3 versus 5.25 (±1.01) cm 3 ), bivariate: p = 0.03, multivariate: HR = 0.40, 95%CI [0.23;0.71], p = 0.002), independently from other factors. This association was found in men (4.43 (±1.22) versus 5.67 (±0.77) cm 3 ), bivariate: p = 0.006, multivariate HR = 0.23, 95%CI [0.06;0.82], p = 0.03) but not in women. ELA is associated with a smaller hippocampus in male but not female depressed in-patients. The reasons for this association should be investigated in further studies.
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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.
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Vegetarian diets and depressive symptoms among men.
Hibbeln, Joseph R; Northstone, Kate; Evans, Jonathan; Golding, Jean
2018-01-01
Vegetarian diets are associate with cardiovascular and other health benefits, but little is known about mental health benefits or risks. To determine whether self-identification of vegetarian dietary habits is associated with significant depressive symptoms in men. Self-report data from 9668 adult male partners of pregnant women in the Avon Longitudinal Study of Parents and Children (ALSPAC) included identification as vegetarian or vegan, dietary frequency data and the Edinburgh Post Natal Depression Scale (EPDS). Continuous and binary outcomes were assessed using multiple linear and logistic regression taking account of potential confounding variables including: age, marital status, employment status, housing tenure, number of children in the household, religion, family history of depression previous childhood psychiatric contact, cigarette and alcohol consumption. Vegetarians [n = 350 (3.6% of sample)], had higher depression scores on average than non-vegetarians (mean difference 0.96 points [95%CI + 0.53, + 1.40]) and a greater risk for EPDS scores above 10 (adjusted OR = 1.67 [95% CI: 1.14,2.44]) than non-vegetarians after adjustment for potential confounding factors. Vegetarian men have more depressive symptoms after adjustment for socio-demographic factors. Nutritional deficiencies (e.g. in cobalamin or iron) are a possible explanation for these findings, however reverse causation cannot be ruled out. Copyright © 2017. Published by Elsevier B.V.
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Instrumental variable methods in comparative safety and effectiveness research.
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.
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Male fertility: psychiatric considerations.
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.
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Russa, A D; Bouma, A; Vernooij, J C M; Jacobs-Reitsma, W; Stegeman, J A
2005-01-01
To determine whether an association exists between partial depopulation of a flock and increased Campylobacter colonization in that flock. Data from 1737 flocks of two Dutch integrators were used. Flocks that experienced partial depopulation were defined as 'exposed' and those that did not as 'nonexposed'. Multivariable modelling was accomplished with, in addition to 'exposure', the independent variables 'age of broilers at slaughter' and 'season' to adjust for possible confounding. The response variable was 'Campylobacter colonization'. The odds ratio (OR) for partial depopulation for integrator A was 0.8 [95% CI (0.4, 1.8)]; for integrator B the OR = 0.8 [95% CI (0.5, 1.3)]. Age and season were confounders: the difference in Campylobacter status between exposed and nonexposed flocks of integrator A could be explained by both variables; for integrator B, only season was associated with Campylobacter status. We found no significant association between partial depopulation and an increased risk of Campylobacter colonization among broiler flocks at final depopulation. This study demonstrates that Campylobacter colonization in a broiler flock is not influenced by the partial depopulation of that flock.
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African ancestry, lung function and the effect of genetics
Wehrmeister, Fernando C.; Hartwig, Fernando P.; Perez-Padilla, Rogelio; Gigante, Denise P.; Barros, Fernando C.; Oliveira, Isabel O.; Ferreira, Gustavo D.; Horta, Bernardo L.
2015-01-01
African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. PMID:25700383
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The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice
Ingvorsen, C; Karp, N A; Lelliott, C J
2017-01-01
Background: Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. Methods: We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. Results: HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. Conclusion: HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes. PMID:28394359
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Downscaled and debiased climate simulations for North America from 21,000 years ago to 2100AD
Lorenz, David J.; Nieto-Lugilde, Diego; Blois, Jessica L.; Fitzpatrick, Matthew C.; Williams, John W.
2016-01-01
Increasingly, ecological modellers are integrating paleodata with future projections to understand climate-driven biodiversity dynamics from the past through the current century. Climate simulations from earth system models are necessary to this effort, but must be debiased and downscaled before they can be used by ecological models. Downscaling methods and observational baselines vary among researchers, which produces confounding biases among downscaled climate simulations. We present unified datasets of debiased and downscaled climate simulations for North America from 21 ka BP to 2100AD, at 0.5° spatial resolution. Temporal resolution is decadal averages of monthly data until 1950AD, average climates for 1950–2005 AD, and monthly data from 2010 to 2100AD, with decadal averages also provided. This downscaling includes two transient paleoclimatic simulations and 12 climate models for the IPCC AR5 (CMIP5) historical (1850–2005), RCP4.5, and RCP8.5 21st-century scenarios. Climate variables include primary variables and derived bioclimatic variables. These datasets provide a common set of climate simulations suitable for seamlessly modelling the effects of past and future climate change on species distributions and diversity. PMID:27377537
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Downscaled and debiased climate simulations for North America from 21,000 years ago to 2100AD.
Lorenz, David J; Nieto-Lugilde, Diego; Blois, Jessica L; Fitzpatrick, Matthew C; Williams, John W
2016-07-05
Increasingly, ecological modellers are integrating paleodata with future projections to understand climate-driven biodiversity dynamics from the past through the current century. Climate simulations from earth system models are necessary to this effort, but must be debiased and downscaled before they can be used by ecological models. Downscaling methods and observational baselines vary among researchers, which produces confounding biases among downscaled climate simulations. We present unified datasets of debiased and downscaled climate simulations for North America from 21 ka BP to 2100AD, at 0.5° spatial resolution. Temporal resolution is decadal averages of monthly data until 1950AD, average climates for 1950-2005 AD, and monthly data from 2010 to 2100AD, with decadal averages also provided. This downscaling includes two transient paleoclimatic simulations and 12 climate models for the IPCC AR5 (CMIP5) historical (1850-2005), RCP4.5, and RCP8.5 21st-century scenarios. Climate variables include primary variables and derived bioclimatic variables. These datasets provide a common set of climate simulations suitable for seamlessly modelling the effects of past and future climate change on species distributions and diversity.
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Effects of pro- and anti-tobacco advertising on nonsmoking adolescents' intentions to smoke.
Straub, Diane M; Hills, Nancy K; Thompson, Pamela J; Moscicki, Anna Barbara
2003-01-01
To determine the effects of pro- and anti-tobacco advertising on nonsmoking adolescents' intention to smoke in a single cohort. All ninth graders at seven public high schools were invited to participate in a study on adolescent tobacco use; 59.0% participated (n = 1229; active positive parental consent required). Adolescents who self-identified as never having smoked even a puff of a cigarette (n = 512) completed a self-administered questionnaire that included questions on intention to smoke in the near future and tobacco advertising. Independent variables used to predict intention included exposure to, recognition of, and receptivity and attitudes toward pro-tobacco and anti-tobacco advertising. Potential confounding variables included gender, race/ethnicity, smoking influences (adult household members, siblings, and friends), socioeconomic status, stress, and depression. Data analysis used logistic regression. 50.5% female, average age 14.9 +/- 0.4 years old at baseline, and varied race. Those variables found to be significant predictors of intention to smoke included: (positive, or increased intention) recognition of brand of favorite advertisement, willingness to use or wear tobacco-branded products, stress, and having friends who smoke and (negative, or decreased intention) agreement with anti-tobacco advertising and having a live-in father who smokes. Although anti-tobacco advertising has a protective effect, it was unable to counteract the effects of pro-tobacco advertising in the same cohort. Copyright Society for Adolescent Medicine, 2003
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ERIC Educational Resources Information Center
Games, Paul A.
1975-01-01
A brief introduction is presented on how multiple regression and linear model techniques can handle data analysis situations that most educators and psychologists think of as appropriate for analysis of variance. (Author/BJG)
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Moon, Graham; Aitken, Grant; Roderick, Paul; Fraser, Simon; Rowlands, Gill
2015-10-01
The relative contributions of functional literacy and functional numeracy to health disparities remain poorly understood in developed world contexts. We seek to unpack their distinctive contributions and to examine how these contributions are framed by place-based deprivation and rurality. We present a multilevel logistic analysis of the 2011 Skills for Life Survey (SfLS), a representative governmental survey of adults aged 16-65 in England. Outcome measures were self-assessed health status and the presence of self-reported long-term health conditions. Exposure variables were functional literacy (FL) and functional numeracy (FN). Age, sex, individual socio-economic status, ethnicity, whether English was a first language, non-UK birthplaces, housing tenure and geography were included as potential confounders and mediators. Geography was measured as area-based deprivation and urban/rural status. FL and FN were both independently associated with self-assessed health status, though the association attenuated after taking account of confounders and mediators. For long-term conditions, the association with FN remained significant following inclusion of confounders and mediators whilst FL attenuated to non-significance. Rurality did not influence these associations. Area deprivation was a significant factor in attenuating the association between FL and self-assessed health status. Policy makers and health professionals will need to be aware of the distinctive impact of FN as well as FL when combating health inequalities, promoting health and managing long-term conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Robustness of meta-analyses in finding gene × environment interactions
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
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Kinship and altruism: a cross-cultural experimental study.
Madsen, Elainie A; Tunney, Richard J; Fieldman, George; Plotkin, Henry C; Dunbar, Robin I M; Richardson, Jean-Marie; McFarland, David
2007-05-01
Humans are characterized by an unusual level of prosociality. Despite this, considerable indirect evidence suggests that biological kinship plays an important role in altruistic behaviour. All previous reports of the influence of kin selection on human altruism have, however, used correlational (rather than experimental) designs, or imposed only a hypothetical or negligible time cost on participants. Since these research designs fail either to control for confounding variables or to meet the criteria required as a test of Hamilton's rule for kin selection (that the altruist pays a true cost), they fail to establish unequivocally whether kin selection plays a role. We show that individuals from two different cultures behave in accordance with Hamilton's rule by acting more altruistically (imposing a higher physical cost upon themselves) towards more closely related individuals. Three possible sources of confound were ruled out: generational effects, sexual attraction and reciprocity. Performance on the task however did not exhibit a perfect linear relationship with relatedness, which might reflect either the intrusion of other variables (e.g. cultural differences in the way kinship is costed) or that our behavioural measure is insufficiently sensitive to fine-tuned differences in the way individuals view their social world. These findings provide the first unequivocal experimental evidence that kinship plays a role in moderating altruistic behaviour. Kinship thus represents a baseline against which individuals pitch other criteria (including reciprocity, prosociality, obligation and a moral sense) when deciding how to behave towards others.
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Understanding logistic regression analysis.
Sperandei, Sandro
2014-01-01
Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed.
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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
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Kazazi, Leila; Foroughan, Mahshid; Nejati, Vahid; Shati, Mohsen
2018-04-01
Age associated cognitive decline or normal cognitive aging is related with lower levels of functioning in real life, and may interfere with maintaining independence and health related quality of life (HRQL). In this study, health related quality of life and cognitive function in community-dwelling older adults were evaluated with the aim of exploring the association between them by adjusting for potential confounders. This cross-sectional study, was implemented on 425 community-dwelling older adults aged 60 and over, between August 2016 and October 2016 in health centers of the municipality of Tehran, Iran, using Mini Mental State Examination (MMSE) to assess cognitive function and Short Form-36 scales (SF-36) to assess HRQL. The relation between HRQL and cognitive function was evaluated by Pearson's correlation coefficient, and the impact of cognitive function on HRQL adjusted for potential confounders was estimated by linear regression model. All analyses were done using SPSS, version 22.0. A positive significant correlation between cognitive function and quality of life (r=0.434; p<0.001) and its dimensions was observed. Two variables of educational level (B=2.704; 95% CI: 2.09 to 3.30; p<0.001) and depression (B=2.554; 95% CI: 2.00 to 3.10; p<0.001) were assumed as potential confounder by changing effect measure after entering the model. After adjusting for potential confounders in regression model, the association between MMSE scores and quality of life persisted (B=2.417; 95% CI: 1.86 to 2.96; p<0.001). The results indicate that cognitive function was associated with HRQL in older adults with age associated cognitive function. Two variables of educational level and depression can affect the relation between cognitive decline and HRQL.
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Burgess, Stephen; Daniel, Rhian M; Butterworth, Adam S; Thompson, Simon G
2015-01-01
Background: Mendelian randomization uses genetic variants, assumed to be instrumental variables for a particular exposure, to estimate the causal effect of that exposure on an outcome. If the instrumental variable criteria are satisfied, the resulting estimator is consistent even in the presence of unmeasured confounding and reverse causation. Methods: We extend the Mendelian randomization paradigm to investigate more complex networks of relationships between variables, in particular where some of the effect of an exposure on the outcome may operate through an intermediate variable (a mediator). If instrumental variables for the exposure and mediator are available, direct and indirect effects of the exposure on the outcome can be estimated, for example using either a regression-based method or structural equation models. The direction of effect between the exposure and a possible mediator can also be assessed. Methods are illustrated in an applied example considering causal relationships between body mass index, C-reactive protein and uric acid. Results: These estimators are consistent in the presence of unmeasured confounding if, in addition to the instrumental variable assumptions, the effects of both the exposure on the mediator and the mediator on the outcome are homogeneous across individuals and linear without interactions. Nevertheless, a simulation study demonstrates that even considerable heterogeneity in these effects does not lead to bias in the estimates. Conclusions: These methods can be used to estimate direct and indirect causal effects in a mediation setting, and have potential for the investigation of more complex networks between multiple interrelated exposures and disease outcomes. PMID:25150977
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Peres, Maria Fernanda Tourinho; Cardia, Nancy; de Mesquita Neto, Paulo; Dos Santos, Patrícia Carla; Adorno, Sérgio
2008-04-01
To analyze the association between police violence and homicide mortality rates taking into consideration the effect of contextual variables. This was an environmental, cross-sectional study that included the 96 census districts in the City of São Paulo. The association between the variables was analyzed using Spearman's rank correlation and simple and multiple regression analysis. Univariate analysis revealed a strong and significant association between homicide mortality coefficients and all the indicators of socioeconomic development and police violence. After controlling for potential confounding factors, the association between police violence and homicide mortality coefficients remained strong and significant. This significance was lost only after control for the size of the resident population. The results indicate that police action that violates basic human rights is not the right answer to urban violence. The combination of homicides from interpersonal violence and deaths from police violence results in negative socialization and promotes further violence.
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Forecasting High-Priority Infectious Disease Surveillance Regions: A Socioeconomic Model
Chan, Emily H.; Scales, David A.; Brewer, Timothy F.; Madoff, Lawrence C.; Pollack, Marjorie P.; Hoen, Anne G.; Choden, Tenzin; Brownstein, John S.
2013-01-01
Background. Few researchers have assessed the relationships between socioeconomic inequality and infectious disease outbreaks at the population level globally. We use a socioeconomic model to forecast national annual rates of infectious disease outbreaks. Methods. We constructed a multivariate mixed-effects Poisson model of the number of times a given country was the origin of an outbreak in a given year. The dataset included 389 outbreaks of international concern reported in the World Health Organization's Disease Outbreak News from 1996 to 2008. The initial full model included 9 socioeconomic variables related to education, poverty, population health, urbanization, health infrastructure, gender equality, communication, transportation, and democracy, and 1 composite index. Population, latitude, and elevation were included as potential confounders. The initial model was pared down to a final model by a backwards elimination procedure. The dependent and independent variables were lagged by 2 years to allow for forecasting future rates. Results. Among the socioeconomic variables tested, the final model included child measles immunization rate and telephone line density. The Democratic Republic of Congo, China, and Brazil were predicted to be at the highest risk for outbreaks in 2010, and Colombia and Indonesia were predicted to have the highest percentage of increase in their risk compared to their average over 1996–2008. Conclusions. Understanding socioeconomic factors could help improve the understanding of outbreak risk. The inclusion of the measles immunization variable suggests that there is a fundamental basis in ensuring adequate public health capacity. Increased vigilance and expanding public health capacity should be prioritized in the projected high-risk regions. PMID:23118271
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The epidemiology of bovine respiratory disease: What is the evidence for preventive measures?
Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.
2010-01-01
Bovine respiratory disease (BRD) is the most common and costly disease of beef cattle in North America. Despite extensive research, industry practices are often more informed by dogma than by fact. Frequently advocated interventions, including vaccination, various processing procedures, and nutritional manipulation, have limited impact on morbidity and mortality. Evidence for use of oral antimicrobials, either in feed or water, appears to be equivocal. In contrast, preconditioning and metaphylaxis have significant scientific evidence of efficacy, with weaning prior to sale potentially being the most important component of preconditioning. The inability to reach more definitive conclusions in preventing BRD may be attributable to difficulties in investigating the disease. Study challenges include potential for extensive confounding, tremendous variability, the multi-factorial nature of the disease, and inadequate methods for diagnosis. PMID:21358927
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COMPOSITE SAMPLING FOR SOIL VOC ANALYSIS
Data published by numerous researchers over the last decade demonstrate that there is a high degree of spatial variability in the measurement of volatile organic compounds (VOCs) in soil at contaminated waste sites. This phenomenon is confounded by the use of a small sample aliqu...
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Childhood Medical and Behavioral Consequences of Maternal Cocaine Use1
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
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Clemens, Tom; Dibben, Chris
2017-04-01
Patterns of adverse birth outcomes vary spatially and there is evidence that this may relate to features of the physical environment such as air pollution. However, other social characteristics of the environment such as levels of crime are relatively understudied. This study examines the association between crime rates and birth weight and prematurity. Maternity inpatient data recorded at birth, including residential postcode, was linked to a representative 5% sample of Scottish Census data and small area crime rates from Scottish Police forces. Coefficients associated with crime were reported from crude and confounder adjusted models predicting low birth weight (< 2500 g), mean birthweight, small for gestational age and prematurity for all singleton live births. Total crime rates were associated with strong and significant reductions in mean birth weight and increases in the risks of both a small for gestational age baby and premature birth. These effects, with the exception of prematurity, were robust to adjustment for individual characteristics including smoking, ethnicity and other socio-economic variables as well as area based confounders including air pollution. Mean birth weight was robust to additional adjustment for neighbourhood income deprivation. The level of crime in a mother's area of residence, which may be a proxy for the degree of threat felt and therefore stress experienced, appears to be an important determinant of the risk of adverse birth outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association.
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Gallagher, Lisa G; Webster, Thomas F; Aschengrau, Ann
2017-03-11
Investigating the effects of prenatal and childhood exposures on behavioral health outcomes in adolescence is challenging given the lengthy period between the exposure and outcomes. We conducted a retrospective cohort study in Cape Cod, Massachusetts to evaluate the impact of prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water on the occurrence of risk-taking behaviors as a teenager. An increased occurrence of risk-taking behaviors, particularly illicit drug use, was observed in those highly exposed to PCE. We hypothesized that there may be other sources of prenatal solvent exposure such as maternal consumption of alcoholic beverages during pregnancy which might modify the previously observed associations between PCE and risk-taking behaviors and so we conducted an exploratory analysis using available cohort data. The current report presents the results of these analyses and describes the difficulties in conducting research on long-term behavioral effects of early life exposures. The exploratory analysis compared a referent group of subjects with no early life exposure to PCE or alcohol (n = 242) to subjects with only alcohol exposure (n = 201), subjects with only PCE exposure (n = 361), and subjects with exposure to both PCE and alcohol (n = 302). Surveys completed by the subject's mother included questions on prenatal alcoholic beverage consumption and available confounding variables such as cigarette smoking and marijuana use. Surveys completed by the subjects included questions on risk-taking behaviors such as alcoholic beverage consumption and illicit drug use as a teenager and available confounding variables. PCE exposure was modeled using a leaching and transport algorithm embedded in water distribution system modeling software that estimated the amount of PCE delivered to a subject's residence during gestation and early childhood. Subjects with early life exposure to both PCE and alcohol had an increased risk of using two or more major drugs as a teen (RR = 1.9 (95% CI 1.2, 3.0)) compared to unexposed subjects. Increased risks for only PCE exposure (RR = 1.6 (95% CI 1.0, 2.4) and only alcohol exposure (RR = 1.3 (95% CI 0.7, 2.1)) were also evident but were smaller than the increased risk associated with both exposures. While available confounding variables were controlled, many relevant social risk factors were not obtained due to limitations in the retrospective study design. This exploratory analysis found evidence for an additive effect of early life exposure to PCE and alcohol on the risk of use of multiple illicit drugs as a teenager. Because of numerous limitations in this retrospective study, further research is needed to examine longstanding behavioral effects of early life exposures. To be most informative, this research should involve long-term prospective data collection.
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A long term study of pulmonary function among US refractory ceramic fibre workers
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
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Borgen, Nicolai T
2014-11-01
This paper addresses the recent discussion on confounding in the returns to college quality literature using the Norwegian case. The main advantage of studying Norway is the quality of the data. Norwegian administrative data provide information on college applications, family relations and a rich set of control variables for all Norwegian citizens applying to college between 1997 and 2004 (N = 141,319) and their succeeding wages between 2003 and 2010 (676,079 person-year observations). With these data, this paper uses a subset of the models that have rendered mixed findings in the literature in order to investigate to what extent confounding biases the returns to college quality. I compare estimates obtained using standard regression models to estimates obtained using the self-revelation model of Dale and Krueger (2002), a sibling fixed effects model and the instrumental variable model used by Long (2008). Using these methods, I consistently find increasing returns to college quality over the course of students' work careers, with positive returns only later in students' work careers. I conclude that the standard regression estimate provides a reasonable estimate of the returns to college quality. Copyright © 2014 Elsevier Inc. All rights reserved.
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Rummo, Pasquale E; Guilkey, David K; Ng, Shu Wen; Meyer, Katie A; Popkin, Barry M; Reis, Jared P; Shikany, James M; Gordon-Larsen, Penny
2017-12-01
The relationship between food environment exposures and diet behaviours is unclear, possibly because the majority of studies ignore potential residual confounding. We used 20 years (1985-1986, 1992-1993 2005-2006) of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study across four US cities (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; Oakland, California) and instrumental variables (IV) regression to obtain causal estimates of longitudinal associations between the percentage of neighbourhood food outlets (per total food outlets within 1 km network distance of respondent residence) and an a priori diet quality score, with higher scores indicating higher diet quality. To assess the presence and magnitude of bias related to residual confounding, we compared results from causal models (IV regression) to non-causal models, including ordinary least squares regression, which does not account for residual confounding at all and fixed-effects regression, which only controls for time-invariant unmeasured characteristics. The mean diet quality score across follow-up was 63.4 (SD=12.7). A 10% increase in fast food restaurants (relative to full-service restaurants) was associated with a lower diet quality score over time using IV regression (β=-1.01, 95% CI -1.99 to -0.04); estimates were attenuated using non-causal models. The percentage of neighbourhood convenience and grocery stores (relative to supermarkets) was not associated with diet quality in any model, but estimates from non-causal models were similarly attenuated compared with causal models. Ignoring residual confounding may generate biased estimated effects of neighbourhood food outlets on diet outcomes and may have contributed to weak findings in the food environment literature. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Tsuchiya, Asuka; Tsutsumi, Yusuke; Yasunaga, Hideo
2016-11-29
Because of a lack of randomized controlled trials and the methodological weakness of currently available observational studies, the benefits of helicopter emergency medical services (HEMS) over ground emergency medical services (GEMS) for major trauma patients remain uncertain. The aim of this retrospective nationwide cohort study was to compare the mortality of adults with serious traumatic injuries who were transported by HEMS and GEMS, and to analyze the effects of HEMS in various subpopulations. Using the Japan Trauma Data Bank, we evaluated all adult patients who had an injury severity score ≥ 16 transported by HEMS or GEMS during the daytime between 2004 and 2014. We compared in-hospital mortality between patients transported by HEMS and GEMS using propensity score matching, inverse probability of treatment weighting and instrumental variable analyses to adjust for measured and unmeasured confounding factors. Eligible patients (n = 21,286) from 192 hospitals included 4128 transported by HEMS and 17,158 transported by GEMS. In the propensity score-matched model, there was a significant difference in the in-hospital mortality between HEMS and GEMS groups (22.2 vs. 24.5%, risk difference -2.3% [95% confidence interval, -4.2 to -0.5]; number needed to treat, 43 [95% confidence interval, 24 to 220]). The inverse probability of treatment weighting (20.8% vs. 23.9%; risk difference, -3.9% [95% confidence interval, -5.7 to -2.1]; number needed to treat, 26 [95% confidence interval, 17 to 48]) and instrumental variable analyses showed similar results (risk difference, -6.5% [95% confidence interval, -9.2 to -3.8]; number needed to treat, 15 [95% confidence interval, 11 to 27]). HEMS transport was significantly associated with lower in-hospital mortality after falls, compression injuries, severe chest injuries, extremity (including pelvic) injuries, and traumatic arrest on arrival to the emergency department. HEMS was associated with a significantly lower mortality than GEMS in adult patients with major traumatic injuries after adjusting for measured and unmeasured confounders.
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Hydrologic impacts of land disturbance and management can be confounded by rainfall variability. As a consequence, attempts to gauge and quantify these effects through streamflow monitoring are typically subject to uncertainties. This paper addresses the quantification and deline...
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Birth Weight, Physical Morbidity, and Mortality: A Population-based Sibling-Comparison Study
Class, Quetzal A.; Rickert, Martin E.; Lichtenstein, Paul; D'Onofrio, Brian M.
2014-01-01
Associations between low birth weight (≤2,500 g) and increased risk of mortality and morbidity provided the foundation for the “developmental origins of health and disease” hypothesis. Previous between-family studies could not control for unmeasured confounders. Therefore, we compared differentially exposed siblings to estimate the extent to which the associations were due to uncontrolled factors. Our population cohort included 3,291,773 persons born in Sweden from 1973 to 2008. Analyses controlled for gestational age, among other covariates, and considered birth weight as both an ordinal and a continuous variable. Outcomes included mortality after 1 year, cardiac-related death, hypertension, ischemic heart disease, pulmonary circulation problems, stroke, and type 2 diabetes mellitus. We fitted fixed-effects models to compare siblings and conducted sensitivity analyses to test alternative explanations. Across the population, the lower the birth weight, the greater the risk of mortality (e.g., cardiac-related death (low birth weight hazard ratio = 2.69, 95% confidence interval: 2.05, 3.53)) and morbidity (e.g., type 2 diabetes mellitus (low birth weight hazard ratio = 1.79, 95% confidence interval: 1.50, 2.14)) outcomes in comparison with normal birth weight. All associations were independent of shared familial confounders and measured covariates. Results emphasize the importance of birth weight as a risk factor for subsequent mortality and morbidity. PMID:24355331
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Time from cervical conization to pregnancy and preterm birth.
Himes, Katherine P; Simhan, Hyagriv N
2007-02-01
To estimate whether the time interval between cervical conization and subsequent pregnancy is associated with risk of preterm birth. Our study is a case control study nested in a retrospective cohort. Women who underwent colposcopic biopsy or conization with loop electrosurgical excision procedure, large loop excision of the transformation zone, or cold knife cone and subsequently delivered at our hospital were identified with electronic databases. Variables considered as possible confounders included maternal race, age, marital status, payor status, years of education, self-reported tobacco use, history of preterm delivery, and dimensions of cone specimen. Conization was not associated with preterm birth or any subtypes of preterm birth. Among women who underwent conization, those with a subsequent preterm birth had a shorter conization-to-pregnancy interval (337 days) than women with a subsequent term birth (581 days) (P=.004). The association between short conization-to-pregnancy interval and preterm birth remained significant when controlling for confounders including race and cone dimensions. The effect of short conization-to-pregnancy interval on subsequent preterm birth was more persistent among African Americans when compared with white women. Women with a short conization-to-pregnancy interval are at increased risk for preterm birth. Women of reproductive age who must have a conization procedure can be counseled that conceiving within 2 to 3 months of the procedure may be associated with an increased risk of preterm birth. II.
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The Impact of Childhood Obesity on Health and Health Service Use.
Kinge, Jonas Minet; Morris, Stephen
2018-06-01
To test the impact of obesity on health and health care use in children, by the use of various methods to account for reverse causality and omitted variables. Fifteen rounds of the Health Survey for England (1998-2013), which is representative of children and adolescents in England. We use three methods to account for reverse causality and omitted variables in the relationship between BMI and health/health service use: regression with individual, parent, and household control variables; sibling fixed effects; and instrumental variables based on genetic variation in weight. We include all children and adolescents aged 4-18 years old. We find that obesity has a statistically significant and negative impact on self-rated health and a positive impact on health service use in girls, boys, younger children (aged 4-12), and adolescents (aged 13-18). The findings are comparable in each model in both boys and girls. Using econometric methods, we have mitigated several confounding factors affecting the impact of obesity in childhood on health and health service use. Our findings suggest that obesity has severe consequences for health and health service use even among children. © Health Research and Educational Trust.
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Brody, Gene H; Miller, Gregory E; Yu, Tianyi; Beach, Steven R H; Chen, Edith
2016-04-01
This study tested the hypothesis that supportive family environments during adolescence buffer exposure to racial discrimination, reducing its impact on biological weathering and its manifestation in cellular aging. Perceived racial discrimination, support in the family environment, and confounder variables were assessed for 3 consecutive years across adolescence in two independent cohorts of African American youth from rural Georgia. DNA was extracted from peripheral blood mononuclear cells collected during young adulthood. Patterns of methylation were used to index the epigenetic ages of these cells and the extent to which they differed from participants' chronological ages. Among youth in supportive family environments, exposure to higher levels of racial discrimination did not forecast greater epigenetic aging. Among youth in less supportive family environments, exposure to higher levels of racial discrimination did forecast greater epigenetic aging. The associations emerged independently of confounder variables, and the results were replicated across the two cohorts. © The Author(s) 2016.
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Instrumental variable methods in comparative safety and effectiveness research†
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
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The health consequences of maquiladora work: women on the US-Mexican border.
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
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NASA Technical Reports Server (NTRS)
Morton, Douglas C.; Nagol, Jyoteshwar; Carabajal, Claudia C.; Rosette, Jacqueline; Palace, Michael; Cook, Bruce D.; Vermote, Eric F.; Harding, David J.; North, Peter R. J.
2016-01-01
Multiple mechanisms could lead to up-regulation of dry-season photosynthesis in Amazon forests, including canopy phenology and illumination geometry. We specifically tested two mechanisms for phenology-driven changes in Amazon forests during dry-season months, and the combined evidence from passive optical and lidar satellite data was incompatible with large net changes in canopy leaf area or leaf reflectance suggested by previous studies. We therefore hypothesized that seasonal changes in the fraction of sunlit and shaded canopies, one aspect of bidirectional reflectance effects in Moderate Resolution Imaging Spectroradiometer (MODIS) data, could alter light availability for dry-season photosynthesis and the photosynthetic capacity of Amazon forests without large net changes in canopy composition. Subsequent work supports the hypothesis that seasonal changes in illumination geometry and diffuse light regulate light saturation in Amazon forests. These studies clarify the physical mechanisms that govern light availability in Amazon forests from seasonal variability in direct and diffuse illumination. Previously, in the debate over light limitation of Amazon forest productivity, seasonal changes in the distribution of light within complex Amazon forest canopies were confounded with dry-season increases in total incoming photosynthetically active radiation. In the accompanying Comment, Saleska et al. do not fully account for this confounding effect of forest structure on photosynthetic capacity.
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Kupek, Emil
2006-03-15
Structural equation modelling (SEM) has been increasingly used in medical statistics for solving a system of related regression equations. However, a great obstacle for its wider use has been its difficulty in handling categorical variables within the framework of generalised linear models. A large data set with a known structure among two related outcomes and three independent variables was generated to investigate the use of Yule's transformation of odds ratio (OR) into Q-metric by (OR-1)/(OR+1) to approximate Pearson's correlation coefficients between binary variables whose covariance structure can be further analysed by SEM. Percent of correctly classified events and non-events was compared with the classification obtained by logistic regression. The performance of SEM based on Q-metric was also checked on a small (N = 100) random sample of the data generated and on a real data set. SEM successfully recovered the generated model structure. SEM of real data suggested a significant influence of a latent confounding variable which would have not been detectable by standard logistic regression. SEM classification performance was broadly similar to that of the logistic regression. The analysis of binary data can be greatly enhanced by Yule's transformation of odds ratios into estimated correlation matrix that can be further analysed by SEM. The interpretation of results is aided by expressing them as odds ratios which are the most frequently used measure of effect in medical statistics.
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Rudolph, Kara E; Sánchez, Brisa N; Stuart, Elizabeth A; Greenberg, Benjamin; Fujishiro, Kaori; Wand, Gary S; Shrager, Sandi; Seeman, Teresa; Diez Roux, Ana V; Golden, Sherita H
2016-03-01
Evidence of the link between job strain and cortisol levels has been inconsistent. This could be due to failure to account for cortisol variability leading to underestimated standard errors. Our objective was to model the relationship between job strain and the whole cortisol curve, accounting for sources of cortisol variability. Our functional mixed-model approach incorporated all available data-18 samples over 3 days-and uncertainty in estimated relationships. We used employed participants from the Multi-Ethnic Study of Atherosclerosis Stress I Study and data collected between 2002 and 2006. We used propensity score matching on an extensive set of variables to control for sources of confounding. We found that job strain was associated with lower salivary cortisol levels and lower total area under the curve. We found no relationship between job strain and the cortisol awakening response. Our findings differed from those of several previous studies. It is plausible that our results were unique to middle- to older-aged racially, ethnically, and occupationally diverse adults and were therefore not inconsistent with previous research among younger, mostly white samples. However, it is also plausible that previous findings were influenced by residual confounding and failure to propagate uncertainty (i.e., account for the multiple sources of variability) in estimating cortisol features. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Ambs, Stefan; Tang, Wei; Zhu, Shuotun; Dorsey, Tiffany H.; Goudie, Megan; Masters, Jonathan G.; Ferguson, Lynnette R.
2018-01-01
Introduction The prostate-specific antigen (PSA) based prostate cancer (PC) screening is currently being debated. The current assessment is to understand the variability of detecting high-risk PC in a NZ cohort in comparison to a US cohort with better PSA screening facilities. Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions with a potential to regulate subsequent PSA levels. Therefore, we wish to understand the influence of tobacco smoking and the AKR1C3 rs12529 gene polymorphism in this variability. Method NZ cohort (n = 376) consisted of 94% Caucasians while the US cohort consisted of African Americans (AA), n = 202, and European Americans (EA), n = 232. PSA level, PC grade and stage at diagnosis were collected from hospital databases for assigning high-risk PC status. Tobacco smoking status and the AKR1C3 rs12529 SNP genotype were considered as confounding variables. Variation of the cumulative % high-risk PC (outcome variable) with increasing PSA intervals (exposure factor) was compared between the cohorts using the Kolmogorov-Smirnov test. Comparisons were carried out with and without stratifications made using confounding variables. Results NZ cohort has been diagnosed at a significantly higher mean age (66.67± (8.08) y) compared to both AA (62.65±8.17y) and EA (64.83+8.56y); median PSA (NZ 8.90ng/ml compared to AA 6.86ng/ml and EA 5.80ng/ml); and Gleason sum (NZ (7) compared EA (6)) (p<0.05). The cumulative % high-risk PC detection shows NZ cohort with a significantly lower diagnosis rates at PSA levels between >6 - <10ng/ml compared to both US groups (p<0.05). These were further compounded significantly by smoking status and genetics. Conclusions High-risk PCs recorded at higher PSA levels in NZ could be due to factors including lower levels of PSA screening and subsequent specialist referrals for biopsies. These consequences could be pronounced among NZ ever smokers carrying the AKR1C3 rs12529 G alleles making them a group that requires increased PSA screening attention. PMID:29920533
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Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST).
Pressman, Alice; Avins, Andrew L; Neuhaus, John; Ackerson, Lynn; Rudd, Peter
2012-05-01
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. 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. 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. 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. 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. Copyright © 2012 Elsevier Inc. All rights reserved.
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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
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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.
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Tan, Chuen Seng; Støer, Nathalie C; Chen, Ying; Andersson, Marielle; Ning, Yilin; Wee, Hwee-Lin; Khoo, Eric Yin Hao; Tai, E-Shyong; Kao, Shih Ling; Reilly, Marie
2017-01-01
The control of confounding is an area of extensive epidemiological research, especially in the field of causal inference for observational studies. Matched cohort and case-control study designs are commonly implemented to control for confounding effects without specifying the functional form of the relationship between the outcome and confounders. This paper extends the commonly used regression models in matched designs for binary and survival outcomes (i.e. conditional logistic and stratified Cox proportional hazards) to studies of continuous outcomes through a novel interpretation and application of logit-based regression models from the econometrics and marketing research literature. We compare the performance of the maximum likelihood estimators using simulated data and propose a heuristic argument for obtaining the residuals for model diagnostics. We illustrate our proposed approach with two real data applications. Our simulation studies demonstrate that our stratification approach is robust to model misspecification and that the distribution of the estimated residuals provides a useful diagnostic when the strata are of moderate size. In our applications to real data, we demonstrate that parity and menopausal status are associated with percent mammographic density, and that the mean level and variability of inpatient blood glucose readings vary between medical and surgical wards within a national tertiary hospital. Our work highlights how the same class of regression models, available in most statistical software, can be used to adjust for confounding in the study of binary, time-to-event and continuous outcomes.
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Comparative effectiveness research in cancer with observational data.
Giordano, Sharon H
2015-01-01
Observational studies are increasingly being used for comparative effectiveness research. These studies can have the greatest impact when randomized trials are not feasible or when randomized studies have not included the population or outcomes of interest. However, careful attention must be paid to study design to minimize the likelihood of selection biases. Analytic techniques, such as multivariable regression modeling, propensity score analysis, and instrumental variable analysis, also can also be used to help address confounding. Oncology has many existing large and clinically rich observational databases that can be used for comparative effectiveness research. With careful study design, observational studies can produce valid results to assess the benefits and harms of a treatment or intervention in representative real-world populations.
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Aschengrau, Ann; Janulewicz, Patricia A.; White, Roberta F.; Vieira, Veronica M.; Gallagher, Lisa G.; Getz, Kelly D.; Webster, Thomas F.; Ozonoff, David M.
2016-01-01
Background Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983 widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. Objectives A retrospective cohort study (“the Cape Cod Health Study”) was undertaken to examine possible health consequences of early life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the impact of prenatal and childhood exposure on neurological outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiological research in this unique setting. Methods Subjects were identified by cross-matching birth certificate and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (N= 1,689), neuropsychological tests (N=63), vision exam (N=63), and magnetic resonance imaging (N=42). Early life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among subjects with prenatal and early childhood PCE exposure to unexposed subjects while considering the impact of confounding variables. Results The study found evidence that early life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical nature of the exposure assessments. Conclusions The Cape Cod Health Study demonstrates how scientists can take advantage of unique “natural experiments” to learn about the health effects of environmental pollution. This body of work has improved our understanding of the long-term health effects of early life exposure to this common environmental contaminant and will help risk assessors and policy makers ensure that U.S. drinking water supplies are safe for vulnerable populations. PMID:27325074
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Jones, Andrew; Button, Emily; Rose, Abigail K; Robinson, Eric; Christiansen, Paul; Di Lemma, Lisa; Field, Matt
2016-03-01
Motivation to drink alcohol can be measured in the laboratory using an ad-libitum 'taste test', in which participants rate the taste of alcoholic drinks whilst their intake is covertly monitored. Little is known about the construct validity of this paradigm. The objective of this study was to investigate variables that may compromise the validity of this paradigm and its construct validity. We re-analysed data from 12 studies from our laboratory that incorporated an ad-libitum taste test. We considered time of day and participants' awareness of the purpose of the taste test as potential confounding variables. We examined whether gender, typical alcohol consumption, subjective craving, scores on the Alcohol Use Disorders Identification Test and perceived pleasantness of the drinks predicted ad-libitum consumption (construct validity). We included 762 participants (462 female). Participant awareness and time of day were not related to ad-libitum alcohol consumption. Males drank significantly more alcohol than females (p < 0.001), and individual differences in typical alcohol consumption (p = 0.04), craving (p < 0.001) and perceived pleasantness of the drinks (p = 0.04) were all significant predictors of ad-libitum consumption. We found little evidence that time of day or participant awareness influenced alcohol consumption. The construct validity of the taste test was supported by relationships between ad-libitum consumption and typical alcohol consumption, craving and pleasantness ratings of the drinks. The ad-libitum taste test is a valid method for the assessment of alcohol intake in the laboratory.
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Peerenboom, L; Collard, R M; Naarding, P; Comijs, H C
2015-08-15
We investigated the association between old age depression and emotional and social loneliness. A cross-sectional study was performed using data from the Netherlands Study of Depression in Older Persons (NESDO). A total of 341 participants diagnosed with a depressive disorder, and 125 non-depressed participants were included. Depression diagnosis was confirmed with the Composite International Diagnostic Interview. Emotional and social loneliness were assessed using the De Jong Gierveld Loneliness Scale. Socio-demographic variables, social support variables, depression characteristics (Inventory of Depressive Symptoms), cognitive functioning (Mini Mental State Examination) and personality factors (the NEO- Five Factor Inventory and the Pearlin Mastery Scale) were considered as possible explanatory factors or confounders. (Multiple) logistic regression analyses were performed. Depression was strongly associated with emotional loneliness, but not with social loneliness. A higher sense of neuroticism and lower sense of mastery were the most important explanatory factors. Also, we found several other explanatory and confounding factors in the association of depression and emotional loneliness; a lower sense of extraversion and higher severity of depression. We performed a cross-sectional observational study. Therefore we cannot add evidence in regard to causation; whether depression leads to loneliness or vice versa. Depression in older persons is strongly associated with emotional loneliness but not with social loneliness. Several personality traits and the severity of depression are important in regard to the association of depression and emotional loneliness. It is important to develop interventions in which both can be treated. Copyright © 2015 Elsevier B.V. All rights reserved.
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Farm-scale variation of soil quality indices and association with edaphic properties
USDA-ARS?s Scientific Manuscript database
Soil organisms are indicators of dynamic soil quality because their community structure and population density are sensitive to management changes. However, edaphic properties can also affect soil organisms and high spatial variability can confound their utility for soil evaluation. In the present...
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Microcounseling Skill Discrimination Scale: A Methodological Note
ERIC Educational Resources Information Center
Stokes, Joseph; Romer, Daniel
1977-01-01
Absolute ratings on the Microcounseling Skill Discrimination Scale (MSDS) confound the individual's use of the rating scale and actual ability to discriminate effective and ineffective counselor behaviors. This note suggests methods of scoring the MSDS that will eliminate variability attributable to response language and improve the validity of…
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D.A. Marquis
1991-01-01
Many studies have shown that initial tree diameter is closely correlated with subsequent tree growth. But initial tree diameter is actually a confounded variable, incorporating both competitive position (crown class) and age.
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Antidepressants and testicular cancer: cause versus association.
Andrade, Chittaranjan
2014-03-01
A data mining study that examined associations between 105 drugs and 55 cancer sites found significant associations between 2 selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and testicular cancer. The study suggested several reasons why these associations merited further investigation. A later study tested specific relationships between 12 antidepressant drugs and testicular cancer and subtypes thereof; whereas significant relationships were again found, these disappeared after adjusting for confounding variables. These 2 studies are educative because they illustrate how false-positive results can easily arise in exploratory research and how confounding may be responsible for statistically significant relationships in study designs that are not randomized controlled trials. © Copyright 2014 Physicians Postgraduate Press, Inc.
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Association of Fatigue With Sarcopenia and its Elements: A Secondary Analysis of SABE-Bogotá
Patino-Hernandez, Daniela; David-Pardo, David Gabriel; Borda, Miguel Germán; Pérez-Zepeda, Mario Ulises; Cano-Gutiérrez, Carlos
2017-01-01
Objective: Sarcopenia, fatigue, and depression are associated with higher mortality rates and adverse outcomes in the aging population. Understanding the association among clinical variables, mainly symptoms, is important for screening and appropriately managing these conditions. The aim of this article is to evaluate the association among sarcopenia and its elements with depression and fatigue. Method: We used cross-sectional data from 2012 SABE (Salud, Bienestar y Envejecimiento)-Bogotá study, which included 2,000 participants of ages ≥60 years. Sarcopenia and its elements were taken as the dependent variable, while fatigue and depression were the main independent variables. We tested the association among these through multiple logistic regression models, which were fitted for each dependent variable and adjusted for confounding variables. Results: Our findings showed that gait speed was associated with fatigue (adjusted odds ratio [OR] = 1.41, 95% confidence interval [CI] = [1.05, 1.90], p = .02) as well as abnormal handgrip strength (adjusted OR = 1.40, 95% CI = [1.02, 1.93], p = .04). No other associations were significant. Conclusion: While sarcopenia and fatigue are not associated, two of the sarcopenia-defining variables are associated with fatigue; this suggests that lack of sarcopenia does not exclude undesirable outcomes related to fatigue in aging adults. Also, the lack of association between sarcopenia-defining elements and depression demonstrates that depression and fatigue are different concepts. PMID:28474000
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2011-01-01
Background Population ageing may threaten the sustainability of future health care systems. Strengthening primary health care, including long-term care, is one of several measures being taken to handle future health care needs and budgets. There is limited and inconsistent evidence on the effect of long-term care on hospital use. We explored the relationship between the total use of long-term care within public primary health care in Norway and the use of hospital beds when adjusting for various effect modifiers and confounders. Methods This national population-based observational study consists of all Norwegians (59% women) older than 66 years (N = 605676) (13.2% of total population) in 2002-2006. The unit of analysis was defined by municipality, age and sex. The association between total number of recipients of long-term care per 1000 inhabitants (LTC-rate) and hospital days per 1000 inhabitants (HD-rate) was analysed in a linear regression model. Modifying and confounding effects of socioeconomic, demographic and geographic variables were included in the final model. We defined a difference in hospitalization rates of more than 1000 days per 1000 inhabitants as clinically important. Results Thirty-one percent of women and eighteen percent of men were long-term care users. Men had higher HD-rates than women. The crude association between LTC-rate and HD-rate was weakly negative. We identified two effect modifiers (age and sex) and two strong confounders (travel time to hospital and mortality). Age and sex stratification and adjustments for confounders revealed a positive statistically significant but not clinically important relationship between LTC-rates and hospitalization for women aged 67-79 years and all men. For women 80 years and over there was a weak but negative relationship which was neither statistically significant nor clinically important. Conclusions We found a weak positive adjusted association between LTC-rates and HD-rates. Opposite to common belief, we found that increased volume of LTC by itself did not reduce pressure on hospitals. There still is a need to study integrated care models for the elderly in the Norwegian setting and to explore further why municipalities far away from hospital achieve lower use of hospital beds. PMID:22029775
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High neuroticism at age 20 predicts history of mental disorders and low self-esteem at age 35.
Lönnqvist, Jan-Erik; Verkasalo, Markku; Mäkinen, Seppo; Henriksson, Markus
2009-07-01
The authors assessed whether neuroticism in emerging adulthood predicts mental disorders and self-esteem in early adulthood after controlling for possible confounding variables. A sample of 69 male military conscripts was initially assessed at age 20 and again as civilians at age 35. The initial assessment included a psychiatric interview, objective indicators of conscript competence, an intellectual performance test, and neuroticism questionnaires. The follow-up assessment included a Structured Clinical Interview for DSM-IV (SCID; First, Spitzer, Gibbon, & Williams, 1996) and the Rosenberg Self-Esteem Scale (Rosenberg, 1965). Neuroticism predicted future mental disorders and low self-esteem beyond more objective indicators of adjustment. The results support the use of neuroticism as a predictor of future mental disorders, even over periods of time when personality is subject to change.
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Psychopathology Differences between Batterers and Nonbatterers: Psychosocial Modifiers.
ERIC Educational Resources Information Center
Hamberger, L. Kevin; Hastings, James E.
Research attention on men who batter their female partners has focused on psychological and personality characteristics of the men. However, occupational status, educational attainment, and abuse history may have been confounded with the personality variables studied. This study made within-group and between-group comparisons of batterers and…
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Partial Identification of Treatment Effects: Applications to Generalizability
ERIC Educational Resources Information Center
Chan, Wendy
2016-01-01
Results from large-scale evaluation studies form the foundation of evidence-based policy. The randomized experiment is often considered the gold standard among study designs because the causal impact of a treatment or intervention can be assessed without threats of confounding from external variables. Policy-makers have become increasingly…
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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)
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Multimedia Learning: Are We Still Asking the Wrong Questions?
ERIC Educational Resources Information Center
Rey, Gunter Daniel
2010-01-01
The article discusses problems that arise from comparing different kinds of presentation modes such as texts, pictures or animations with regard to learning outcome. These comparisons are confounded with or depend on other variables like quality of the instructional design, learning content, familiarity with the presentation mode as well as…
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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.
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Design approaches to experimental mediation☆
Pirlott, Angela G.; MacKinnon, David P.
2016-01-01
Identifying causal mechanisms has become a cornerstone of experimental social psychology, and editors in top social psychology journals champion the use of mediation methods, particularly innovative ones when possible (e.g. Halberstadt, 2010, Smith, 2012). Commonly, studies in experimental social psychology randomly assign participants to levels of the independent variable and measure the mediating and dependent variables, and the mediator is assumed to causally affect the dependent variable. However, participants are not randomly assigned to levels of the mediating variable(s), i.e., the relationship between the mediating and dependent variables is correlational. Although researchers likely know that correlational studies pose a risk of confounding, this problem seems forgotten when thinking about experimental designs randomly assigning participants to levels of the independent variable and measuring the mediator (i.e., “measurement-of-mediation” designs). Experimentally manipulating the mediator provides an approach to solving these problems, yet these methods contain their own set of challenges (e.g., Bullock, Green, & Ha, 2010). We describe types of experimental manipulations targeting the mediator (manipulations demonstrating a causal effect of the mediator on the dependent variable and manipulations targeting the strength of the causal effect of the mediator) and types of experimental designs (double randomization, concurrent double randomization, and parallel), provide published examples of the designs, and discuss the strengths and challenges of each design. Therefore, the goals of this paper include providing a practical guide to manipulation-of-mediator designs in light of their challenges and encouraging researchers to use more rigorous approaches to mediation because manipulation-of-mediator designs strengthen the ability to infer causality of the mediating variable on the dependent variable. PMID:27570259
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Design approaches to experimental mediation.
Pirlott, Angela G; MacKinnon, David P
2016-09-01
Identifying causal mechanisms has become a cornerstone of experimental social psychology, and editors in top social psychology journals champion the use of mediation methods, particularly innovative ones when possible (e.g. Halberstadt, 2010, Smith, 2012). Commonly, studies in experimental social psychology randomly assign participants to levels of the independent variable and measure the mediating and dependent variables, and the mediator is assumed to causally affect the dependent variable. However, participants are not randomly assigned to levels of the mediating variable(s), i.e., the relationship between the mediating and dependent variables is correlational. Although researchers likely know that correlational studies pose a risk of confounding, this problem seems forgotten when thinking about experimental designs randomly assigning participants to levels of the independent variable and measuring the mediator (i.e., "measurement-of-mediation" designs). Experimentally manipulating the mediator provides an approach to solving these problems, yet these methods contain their own set of challenges (e.g., Bullock, Green, & Ha, 2010). We describe types of experimental manipulations targeting the mediator (manipulations demonstrating a causal effect of the mediator on the dependent variable and manipulations targeting the strength of the causal effect of the mediator) and types of experimental designs (double randomization, concurrent double randomization, and parallel), provide published examples of the designs, and discuss the strengths and challenges of each design. Therefore, the goals of this paper include providing a practical guide to manipulation-of-mediator designs in light of their challenges and encouraging researchers to use more rigorous approaches to mediation because manipulation-of-mediator designs strengthen the ability to infer causality of the mediating variable on the dependent variable.
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What is the association between wealth and mental health?
Carter, K N; Blakely, T; Collings, S; Imlach Gunasekara, F; Richardson, K
2009-03-01
Socioeconomic inequalities in mental health have been shown in a number of populations. This study aims to investigate the association between asset wealth and psychological distress in New Zealand and whether it is independent of other socioeconomic measures and baseline health status. Data for this study were from the first three waves of the Survey of Families, Income and Employment (SoFIE) conducted in New Zealand (2002-2004/05) (n = 15 340). The Kessler-10 was used as a measure of psychological distress. The association of quintiles of wealth with psychological distress was investigated using logistic regression, controlling for confounders, socioeconomic variables and prior health status. The odds ratio (OR) of reporting high psychological distress were greater in the lowest wealth quintile compared with the highest (OR 3.06, 95% CI 2.68 to 3.50). Adjusting for age and sex did not alter the relationship; however, adjusting for income and area deprivation attenuated the OR to 1.73 (95% CI 1.48 to 2.04). Further controlling for baseline health status reduced the OR to 1.45 (95% CI 1.23 to 1.71), although the confidence interval still excluded the null. Inequalities in wealth are strongly associated with psychological distress, over and above other confounding demographic variables and baseline health status. Much, but not all, of that association is confounded by adult socioeconomic position. This suggests that policy measures to improve asset wealth, through savings and home ownership, may have positive health implications and help to reduce health inequalities.
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Multisample adjusted U-statistics that account for confounding covariates.
Satten, Glen A; Kong, Maiying; Datta, Somnath
2018-06-19
Multisample U-statistics encompass a wide class of test statistics that allow the comparison of 2 or more distributions. U-statistics are especially powerful because they can be applied to both numeric and nonnumeric data, eg, ordinal and categorical data where a pairwise similarity or distance-like measure between categories is available. However, when comparing the distribution of a variable across 2 or more groups, observed differences may be due to confounding covariates. For example, in a case-control study, the distribution of exposure in cases may differ from that in controls entirely because of variables that are related to both exposure and case status and are distributed differently among case and control participants. We propose to use individually reweighted data (ie, using the stratification score for retrospective data or the propensity score for prospective data) to construct adjusted U-statistics that can test the equality of distributions across 2 (or more) groups in the presence of confounding covariates. Asymptotic normality of our adjusted U-statistics is established and a closed form expression of their asymptotic variance is presented. The utility of our approach is demonstrated through simulation studies, as well as in an analysis of data from a case-control study conducted among African-Americans, comparing whether the similarity in haplotypes (ie, sets of adjacent genetic loci inherited from the same parent) occurring in a case and a control participant differs from the similarity in haplotypes occurring in 2 control participants. Copyright © 2018 John Wiley & Sons, Ltd.
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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.
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Bilingualism and Cognitive Reserve: A Critical Overview and a Plea for Methodological Innovations
Calvo, Noelia; García, Adolfo M.; Manoiloff, Laura; Ibáñez, Agustín
2016-01-01
The decline of cognitive skills throughout healthy or pathological aging can be slowed down by experiences which foster cognitive reserve (CR). Recently, some studies on Alzheimer's disease have suggested that CR may be enhanced by life-long bilingualism. However, the evidence is inconsistent and largely based on retrospective approaches featuring several methodological weaknesses. Some studies demonstrated at least 4 years of delay in dementia symptoms, while others did not find such an effect. Moreover, various methodological aspects vary from study to study. The present paper addresses contradictory findings, identifies possible lurking variables, and outlines methodological alternatives thereof. First, we characterize possible confounding factors that may have influenced extant results. Our focus is on the criteria to establish bilingualism, differences in sample design, the instruments used to examine cognitive skills, and the role of variables known to modulate life-long cognition. Second, we propose that these limitations could be largely circumvented through experimental approaches. Proficiency in the non-native language can be successfully assessed by combining subjective and objective measures; confounding variables which have been distinctively associated with certain bilingual groups (e.g., alcoholism, sleep disorders) can be targeted through relevant instruments; and cognitive status might be better tapped via robust cognitive screenings and executive batteries. Moreover, future research should incorporate tasks yielding predictable patterns of contrastive performance between bilinguals and monolinguals. Crucially, these include instruments which reveal bilingual disadvantages in vocabulary, null effects in working memory, and advantages in inhibitory control and other executive functions. Finally, paradigms tapping proactive interference (which assess the disruptive effect of long-term memory on newly learned information) could also offer useful data, since this phenomenon seems to be better managed by bilinguals and it becomes conspicuous in early stages of dementia. Such considerations may shed light not just on the relationship between bilingualism and CR, but also on more general mechanisms of cognitive compensation. PMID:26793100
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Tessari, Ana Aparecida; Giehl, Maruí Weber Corseuil; Schneider, Ione Jayce Ceola; González-Chica, David Alejandro
2016-12-01
To analyze the effects of anthropometric measures change on quality of life (QoL) in elderly, using measured anthropometric data on body mass index (BMI) and waist circumference (WC). Population-based cohort study investigating a sample of elderly (≥60) assessed in 2009 (n = 1705) and followed up in 2013 (n = 1197). QoL was evaluated in 2013 using the CASP-19. Variables evaluated as exposure including BMI and WC in 2009 (both standardized), categories of anthropometric measures change from 2009 to 2013 (excess weight = BMI ≥ 25.0 kg/m 2 ; large WC = top quartile), and the absolute BMI and WC change in same period. Multivariate linear regressions adjusted for possible confounding factors and mediators were used. Both BMI and WC at baseline were associated with lower QoL scores, even after adjustment for confounding variables (β BMI = -0.9; 95 % CI -1.5; -0.3 and β WC = -1.0; 95 % CI -1.7; -0.4). Additionally, QoL scores were lower among elderly with excess weight (β = -1.4; 95 % CI -2.9; 0.0) or large WC (β = -3.3; 95 % CI -5.2; -1.4) in both waves than among those whose BMI and WC were always normal, but changes in anthropometric measures did not affect QoL. The presence of chronic diseases was a partial mediator of these associations, especially for effects of BMI change. Anthropometric measures change treated as a continuous variable was not associated with QoL. Having excess weight and large WC in both waves was associated with lower QoL scores in elderly, but changing the anthropometric measures did not affect this outcome. Maintaining weight and WC within normal limits during aging can help to preserve QoL.
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Legros, S.; Mialet-Serra, I.; Caliman, J.-P.; Siregar, F. A.; Clément-Vidal, A.; Dingkuhn, M.
2009-01-01
Background and Aims Oil palm flowering and fruit production show seasonal maxima whose causes are unknown. Drought periods confound these rhythms, making it difficult to analyse or predict dynamics of production. The present work aims to analyse phenological and growth responses of adult oil palms to seasonal and inter-annual climatic variability. Methods Two oil palm genotypes planted in a replicated design at two sites in Indonesia underwent monthly observations during 22 months in 2006–2008. Measurements included growth of vegetative and reproductive organs, morphology and phenology. Drought was estimated from climatic water balance (rainfall – potential evapotranspiration) and simulated fraction of transpirable soil water. Production history of the same plants for 2001–2005 was used for inter-annual analyses. Key Results Drought was absent at the equatorial Kandista site (0°55′N) but the Batu Mulia site (3°12′S) had a dry season with variable severity. Vegetative growth and leaf appearance rate fluctuated with drought level. Yield of fruit, a function of the number of female inflorescences produced, was negatively correlated with photoperiod at Kandista. Dual annual maxima were observed supporting a recent theory of circadian control. The photoperiod-sensitive phases were estimated at 9 (or 9 + 12 × n) months before bunch maturity for a given phytomer. The main sensitive phase for drought effects was estimated at 29 months before bunch maturity, presumably associated with inflorescence sex determination. Conclusion It is assumed that seasonal peaks of flowering in oil palm are controlled even near the equator by photoperiod response within a phytomer. These patterns are confounded with drought effects that affect flowering (yield) with long time-lag. Resulting dynamics are complex, but if the present results are confirmed it will be possible to predict them with models. PMID:19748909
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Bilingualism and Cognitive Reserve: A Critical Overview and a Plea for Methodological Innovations.
Calvo, Noelia; García, Adolfo M; Manoiloff, Laura; Ibáñez, Agustín
2015-01-01
The decline of cognitive skills throughout healthy or pathological aging can be slowed down by experiences which foster cognitive reserve (CR). Recently, some studies on Alzheimer's disease have suggested that CR may be enhanced by life-long bilingualism. However, the evidence is inconsistent and largely based on retrospective approaches featuring several methodological weaknesses. Some studies demonstrated at least 4 years of delay in dementia symptoms, while others did not find such an effect. Moreover, various methodological aspects vary from study to study. The present paper addresses contradictory findings, identifies possible lurking variables, and outlines methodological alternatives thereof. First, we characterize possible confounding factors that may have influenced extant results. Our focus is on the criteria to establish bilingualism, differences in sample design, the instruments used to examine cognitive skills, and the role of variables known to modulate life-long cognition. Second, we propose that these limitations could be largely circumvented through experimental approaches. Proficiency in the non-native language can be successfully assessed by combining subjective and objective measures; confounding variables which have been distinctively associated with certain bilingual groups (e.g., alcoholism, sleep disorders) can be targeted through relevant instruments; and cognitive status might be better tapped via robust cognitive screenings and executive batteries. Moreover, future research should incorporate tasks yielding predictable patterns of contrastive performance between bilinguals and monolinguals. Crucially, these include instruments which reveal bilingual disadvantages in vocabulary, null effects in working memory, and advantages in inhibitory control and other executive functions. Finally, paradigms tapping proactive interference (which assess the disruptive effect of long-term memory on newly learned information) could also offer useful data, since this phenomenon seems to be better managed by bilinguals and it becomes conspicuous in early stages of dementia. Such considerations may shed light not just on the relationship between bilingualism and CR, but also on more general mechanisms of cognitive compensation.
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Roll-Tilt Perception Using a Somatosensory Bar Task
NASA Technical Reports Server (NTRS)
Black, F. O.; Wade, S. W.; Arshi, A.
1999-01-01
Visual estimates of roll-tilt perception during static roll-tilt are confounded by an offset due to the ocular counterroll that simultaneously occurs. An alternative, non-visual ('somatosensory') measure of roll-tilt perception was developed which is not contaminated by this offset. The aims of this study were to determine: 1) inter-subject variability of somatosensory settings across test session in normal subjects and patients with unilateral or bilateral vestibular loss and 2) intra-subject variability of settings across test session in normal subjects.
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Saez, Marc; Barceló, Maria A; Farrerons, Mònica; López-Casasnovas, Guillem
2018-06-08
A number of factors contribute to attention deficit hyperactivity disorder (ADHD) and although they are not fully known, the occurrence of ADHD seems to be a consequence of an interaction between multiple genetic and environmental factors. However, apart from pesticides, the evidence is inadequate and inconsistent as it differs not only in the population and time period analysed, but also in the type of study, the control of the confounding variables and the statistical methods used. In the latter case, the studies also differ in the adjustment of spatial and temporal variability. Our objective here, is to provide evidence on an association between environmental factors and ADHD. In our study, we used a population-based retrospective cohort in which we matched cases and controls (children free of the disease) by sex and year of birth (n = 5193, 78.9% boys). The cases were children born between 1998 and 2012 and diagnosed with ADHD (n = 116). To evaluate whether there was a geographical pattern in the incidence of ADHD, we first represented the smoothed standardized incidence rates on a map of the region being studied. We then estimated the probability of being a case by using a generalized liner mixed model with a binomial link. As explanatory variables of interest, we included the following environmental variables: distance to agricultural areas, distance to roads (stratified into three categories according to traffic density and intensity), distance to petrol stations, distance to industrial estates, and land use. We control for both observed (individual and family specific variables and deprivation index) and unobserved confounders (in particular, individual and familial heterogeneity). In addition, we adjusted for spatial extra variability. We found a north-south pattern containing two clusters (one in the centre of the study region and another in the south) in relation to the risk of developing ADHD. The results from the multivariate model suggest that these clusters could be related to some of the environmental variables. Specifically, living within 100 m from an agricultural area or a residential street and/or living fewer than 300 m from a motorway, dual carriageway or one of the industrial estates analysed was associated (statistically significant) with an increased risk of ADHD. Our results indicate that some environmental factors could be associated with ADHD occurring, particularly those associated with exposure to pesticides, organochlorine compounds and air pollutants because of traffic. Copyright © 2018 Elsevier Inc. All rights reserved.
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Prenatal depression effects and interventions: a review.
Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria
2010-12-01
This review covers research on the negative effects of prenatal depression and cortisol on fetal growth, prematurity and low birthweight. Although prenatal depression and cortisol were typically measured at around 20 weeks gestation, other research suggests the stability of depression and cortisol levels across pregnancy. Women with Dysthymia as compared to Major Depression Disorder had higher cortisol levels, and their newborns had lower gestational age and birthweight. The cortisol effects in these studies were unfortunately confounded by low serotonin and low dopamine levels which in themselves could contribute to non-optimal pregnancy outcomes. The negative effects of depression and cortisol were also potentially confounded by comorbid anxiety, by demographic factors including younger age, less education and lower SES of the mothers and by the absence of a partner or a partner who was unhappy about the pregnancy or a partner who was depressed. Substance use (especially caffeine use) was still another risk factor. All of these problems including prenatal depression, elevated cortisol, prematurity and low birthweight and even postpartum depression have been reduced by prenatal massage therapy provided by the women's partners. Massage therapy combined with group interpersonal psychotherapy was also effective for reducing depression and cortisol levels. Several limitations of these studies were noted and suggestions for future research included exploring other predictor variables like progesterone/estriol ratios, immune factors and genetic determinants. Further research is needed both on the potential use of cortisol as a screening measure and the use of other therapies that might reduce prenatal depression and cortisol in the women and prematurity and low birthweight in their infants. Copyright © 2010 Elsevier Inc. All rights reserved.
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Iqbal, M. Bilal; Robinson, Simon D.; Ding, Lillian; Fung, Anthony; Aymong, Eve; Chan, Albert W.; Hodge, Steven; Della Siega, Anthony; Nadra, Imad J.
2016-01-01
Background Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased. Methods We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods. Results A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis. Conclusions In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data. PMID:26870950
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Obesity and the community food environment: a systematic review.
Holsten, Joanna E
2009-03-01
To examine the relationship between obesity and the community and/or consumer food environment. A comprehensive literature search of multiple databases was conducted and seven studies were identified for review. Studies were selected if they measured BMI and environmental variables related to food outlets. Environmental variables included the geographic arrangement of food stores or restaurants in communities and consumer conditions such as food price and availability within each outlet. The study designs, methods, limitations and results related to obesity and the food environment were reviewed, and implications for future research were synthesized. The reviewed studies used cross-sectional designs to examine the community food environment defined as the number per capita, proximity or density of food outlets. Most studies indirectly identified food outlets through large databases. The studies varied substantially in sample populations, outcome variables, units of measurement and data analysis. Two studies did not find any significant association between obesity rates and community food environment variables. Five studies found significant results. Many of the studies were subject to limitations that may have mitigated the validity of the results. Research examining obesity and the community or consumer food environment is at an early stage. The most pertinent gaps include primary data at the individual level, direct measures of the environment, studies examining the consumer environment and study designs involving a time sequence. Future research should directly measure multiple levels of the food environment and key confounders at the individual level.
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Social Conditions and High Levels of Dental Caries in Five-year-old Children in Brazil.
Dantas Cabral de Melo, Márcia M; de Souza, Wayner Vieira; Tavares, Maria Cristina; de Lima, Maria Luiza Carvalho; Jamelli, Silvia; Couto, Geraldo Bosco Lindoso
2015-01-01
To identify factors associated with dental caries experience in at least four primary teeth in five-year-old Brazilian children. This was a case-control study, part of a prior investigation of the prevalence of dental caries in the primary dentition of five-year-old children conducted in 2006 in public health services in Recife, Brazil. Study patients had a decayed, missing, and filled teeth [dmft] score ≥ 4 and controls had a dmft score ≤ 3. The cutoff point was based on the dmft scores mean value of the study population. Categories of independent variables were sociodemographic, family structure, oral health behavior, and use of oral health services. Crude odds ratios and 95% CI were calculated. Variables associated with dmft greater than or equal to four at a significance level of P≤.20 in univariate analyses were included in multivariate logistic regression models using a backward stepwise variable selection method and permanence criterion in the final model of P≤.10. The study included 479 children (171 study patients and 308 controls). After controlling for confounding variables, factors associated with a dmft score ≥ 4 were children living in households with at least six people, residence in a poor area, caregiver's low educational level, consumption of sweets between meals, and the reason for and location of oral health care seeking. Most factors associated with high levels of dental caries in five-year-old children were related to the social conditions in which they lived.
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Carroll, Robert; Metcalfe, Chris; Steeg, Sarah; Davies, Neil M; Cooper, Jayne; Kapur, Nav; Gunnell, David
2016-01-01
Clinical guidelines have recommended psychosocial assessment of self-harm patients for years, yet estimates of its impact on the risk of repeat self-harm vary. Assessing the association of psychosocial assessment with risk of repeat self-harm is challenging due to the effects of confounding by indication. We analysed data from a cohort study of 15,113 patients presenting to the emergency departments of three UK hospitals to investigate the association of psychosocial assessment with risk of repeat hospital presentation for self-harm. Time of day of hospital presentation was used as an instrument for psychosocial assessment, attempting to control for confounding by indication. Conventional regression analysis suggested psychosocial assessment was not associated with risk of repeat self-harm within 12 months (Risk Difference (RD) 0.00 95% confidence interval (95%CI) -0.01 to 0.02). In contrast, IV analysis suggested risk of repeat self-harm was reduced by 18% (RD -0.18, 95%CI -0.32 to -0.03) in those patients receiving a psychosocial assessment. However, the instrument of time of day did not remove all potential effects of confounding by indication, suggesting the IV effect estimate may be biased. We found that psychosocial assessments reduce risk of repeat self-harm. This is in-line with other non-randomised studies based on populations in which allocation to assessment was less subject to confounding by indication. However, as our instrument did not fully balance important confounders across time of day, the IV effect estimate should be interpreted with caution.
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Shen, Xia; De Jonge, Jennifer; Forsberg, Simon K. G.; Pettersson, Mats E.; Sheng, Zheya; Hennig, Lars; Carlborg, Örjan
2014-01-01
As Arabidopsis thaliana has colonized a wide range of habitats across the world it is an attractive model for studying the genetic mechanisms underlying environmental adaptation. Here, we used public data from two collections of A. thaliana accessions to associate genetic variability at individual loci with differences in climates at the sampling sites. We use a novel method to screen the genome for plastic alleles that tolerate a broader climate range than the major allele. This approach reduces confounding with population structure and increases power compared to standard genome-wide association methods. Sixteen novel loci were found, including an association between Chromomethylase 2 (CMT2) and temperature seasonality where the genome-wide CHH methylation was different for the group of accessions carrying the plastic allele. Cmt2 mutants were shown to be more tolerant to heat-stress, suggesting genetic regulation of epigenetic modifications as a likely mechanism underlying natural adaptation to variable temperatures, potentially through differential allelic plasticity to temperature-stress. PMID:25503602
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Evaluating disease management program effectiveness: an introduction to survival analysis.
Linden, Ariel; Adams, John L; Roberts, Nancy
2004-01-01
Currently, the most widely used method in the disease management industry for evaluating program effectiveness is 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 plausible rationale explaining the change from baseline. Survival analysis allows for the inclusion of data from censored cases, those subjects who either "survived" the program without experiencing the event (e.g., achievement of target clinical levels, hospitalization) or left the program prematurely, due to disenrollement from the health plan or program, or were lost to follow-up. Additionally, independent variables may be included in the model to help explain the variability in the outcome measure. In order to maximize the potential of this statistical method, validity of the model and research design must be assured. This paper reviews survival analysis as an alternative, and more appropriate, approach to evaluating DM program effectiveness than the current total population approach.
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Pediatric sleep problems and social-emotional problems. A population-based study.
Hysing, Mari; Sivertsen, Børge; Garthus-Niegel, Susan; Eberhard-Gran, Malin
2016-02-01
To examine the association between sleep and social-emotional development in two-year-old toddlers. The study is part of a longitudinal cohort study, the Akershus Birth Cohort Study, which targeted all women giving birth at Akershus University Hospital in Norway. The current study is from the fourth round of the study, including 2014 women two years after delivery. The Brief Infant Sleep Questionnaire (BISQ) and the Ages and Stages Questionnaire: Social Emotional (ASQ:SE) were filled out by the mothers and were used to assess toddler sleep, and social-emotional development, respectively. Other domains of development (communication problems, gross motor problems, and fine motor problems) were assessed with the Ages and Stages Questionnaire (ASQ). Confirmatory factor analysis was conducted on the ASQ:SE, and logistic regression analyses were used to examine both crude associations between sleep variables and social-emotional problems, and adjusting for potential confounders. The mean sleep duration of the toddlers was 12h and 27 min; the majority of the children (54%) had 1-2 awakenings per night, while 10% of the children had a sleep onset latency of more than 30 min. All sleep parameters, including short sleep duration, nocturnal awakenings and sleep onset problems, were significantly associated with social-emotional problems in a dose-response manner. For example, sleeping less than 11h per night was associated with a five-fold increase in the odds of social-emotional problems, compared to sleeping 13-14 h per night. Adjusting for potential confounders, including maternal age, maternal education, marital status, parity, gestational age, child birth-weight and other developmental problems, did not, or only slightly, attenuate the associations between any of the sleep variables and social-emotional problems. Short sleep duration, nocturnal awakenings and sleep onset problems were all associated with higher odds of social-emotional problems, even after accounting for developmental problems and demographic factors. Thus, a broad assessment of sleep and social-emotional problems when toddlers present with either can be useful. Copyright © 2016. Published by Elsevier Inc.
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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.
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Brunwasser, Steven M; Gebretsadik, Tebeb; Gold, Diane R; Turi, Kedir N; Stone, Cosby A; Datta, Soma; Gern, James E; Hartert, Tina V
2018-01-01
The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0-2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders. We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma.
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Maternal depressive symptoms and early childhood cognitive development: a meta-analysis.
Liu, Y; Kaaya, S; Chai, J; McCoy, D C; Surkan, P J; Black, M M; Sutter-Dallay, A-L; Verdoux, H; Smith-Fawzi, M C
2017-03-01
Previous findings have been mixed regarding the relationship between maternal depressive symptoms and child cognitive development. The objective of this study was to systematically review relevant literature and to perform a meta-analysis. Three electronic databases (PubMed, EMBASE, PsycINFO) were searched. Initial screening was conducted independently by two reviewers. Studies selected for detailed review were read in full and included based on a set of criteria. Data from selected studies were abstracted onto a standardized form. Meta-analysis using the inverse variance approach and random-effects models was conducted. The univariate analysis of 14 studies revealed that maternal depressive symptoms are related to lower cognitive scores among children aged ⩽56 months (Cohen's d = -0.25, 95% CI -0.39 to -0.12). The synthesis of studies controlling for confounding variables showed that the mean cognitive score for children 6-8 weeks post-partum whose mothers had high depressive symptoms during the first few weeks postpartum was approximately 4.2 units lower on the Mental Developmental Index (MDI) of the Bayley Scales of Infant and Toddler Development (BSID) compared with children with non-symptomatic mothers (B̂ = -4.17, 95% CI -8.01 to -0.32). The results indicated that maternal depressive symptoms are related to lower cognitive scores in early infancy, after adjusting for confounding factors. An integrated approach for supporting child cognitive development may include program efforts that promote maternal mental health in addition to family economic wellbeing, responsive caregiving, and child nutrition.
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Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST)
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
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Loneragan, Guy H.; Thomson, Daniel U.; Scott, H. Morgan
2014-01-01
The United States Food and Drug Administration (FDA) approved two β-adrenergic agonists (βAA) for in-feed administration to cattle fed in confinement for human consumption. Anecdotal reports have generated concern that administration of βAA might be associated with an increased incidence of cattle deaths. Our objectives, therefore, were to a) quantify the association between βAA administration and mortality in feedlot cattle, and b) explore those variables that may confound or modify this association. Three datasets were acquired for analysis: one included information from randomized and controlled clinical trials of the βAA ractopamine hydrochloride, while the other two were observational data on zilpaterol hydrochloride administration to large numbers of cattle housed, fed, and cared for using routine commercial production practices in the U.S. Various population and time at-risk models were developed to explore potential βAA relationships with mortality, as well as the extent of confounding and effect modification. Measures of effect were relatively consistent across datasets and models in that the cumulative risk and incidence rate of death was 75 to 90% greater in animals administered the βAA compared to contemporaneous controls. During the exposure period, 40 to 50% of deaths among groups administered the βAA were attributed to administration of the drug. None of the available covariates meaningfully confounded the relationship between βAA and increased mortality. Only month of slaughter, presumably a proxy for climate, consistently modified the effect in that the biological association was generally greatest during the warmer months of the year. While death is a rare event in feedlot cattle, the data reported herein provide compelling evidence that mortality is nevertheless increased in response to administration of FDA-approved βAA and represents a heretofore unquantified adverse drug event. PMID:24621596
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Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R
2017-06-05
Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. Published by Elsevier Ltd.
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Omar, Dashne; Ryan, Tracy; Carson, Alan; Bak, Thomas H; Torrens, Lorna; Whittle, Ian
2014-12-01
The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.
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Small and Large Number Processing in Infants and Toddlers with Williams Syndrome
ERIC Educational Resources Information Center
Van Herwegen, Jo; Ansari, Daniel; Xu, Fei; Karmiloff-Smith, Annette
2008-01-01
Previous studies have suggested that typically developing 6-month-old infants are able to discriminate between small and large numerosities. However, discrimination between small numerosities in young infants is only possible when variables continuous with number (e.g. area or circumference) are confounded. In contrast, large number discrimination…
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Using Learning Analytics to Characterize Student Experimentation Strategies in Engineering Design
ERIC Educational Resources Information Center
Vieira, Camilo; Goldstein, Molly Hathaway; Purzer, Senay; Magana, Alejandra J.
2016-01-01
Engineering design is a complex process both for students to participate in and for instructors to assess. Informed designers use the key strategy of conducting experiments as they test ideas to inform next steps. Conversely, beginning designers experiment less, often with confounding variables. These behaviours are not easy to assess in…
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Growth and physiology of aspen supplied with different fertilizer addition rates
Mark D. Coleman; Richard E. Dickson; J.G. Isebrands
1998-01-01
Variable internal plant nutrient content may confound plant response to environmental stress. Plant nutrient content may be controlled with relative addition rate techniques in solution culture. However, because raising large numbers of plants in flowing solution culture is difficult. we investieated the feasibility of raisine plants in soil mix using relative...
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Neighborhood Frequency Effect in Chinese Word Recognition: Evidence from Naming and Lexical Decision
ERIC Educational Resources Information Center
Li, Meng-Feng; Gao, Xin-Yu; Chou, Tai-Li; Wu, Jei-Tun
2017-01-01
Neighborhood frequency is a crucial variable to know the nature of word recognition. Different from alphabetic scripts, neighborhood frequency in Chinese is usually confounded by component character frequency and neighborhood size. Three experiments were designed to explore the role of the neighborhood frequency effect in Chinese and the stimuli…
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Impact of Trauma Work on Social Work Clinicians: Empirical Findings.
ERIC Educational Resources Information Center
Cunningham, Maddy
2003-01-01
Describes a study of social work clinicians working with two types of trauma: sexual abuse and cancer. The effect of clinician's cognitive schemas and the confounding variables of personal history of abuse and years' experience are described. Clinicians who worked primarily with clients who were sexually abused reported more disruptions in…
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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…
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Long-Term Positive Associations between Music Lessons and IQ
ERIC Educational Resources Information Center
Schellenberg, E. Glenn
2006-01-01
In Study 1 (N = 147), duration of music lessons was correlated positively with IQ and with academic ability among 6-to 11-year-olds, even when potential confounding variables (i.e., family income, parents' education, involvement in nonmusical activities) were held constant. In Study 2 (N = 150), similar but weaker associations between playing…
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Summary. Measures of health outcomes are collinear with meteorology and air quality, making analysis of connections between human health and air quality difficult. The purpose of this analysis was to determine time scales and periods shared by the variables of interest (and...
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Influences of Phonological Context on Tense Marking in Spanish-English Dual Language Learners
ERIC Educational Resources Information Center
Combiths, Philip N.; Barlow, Jessica A.; Potapova, Irina; Pruitt-Lord, Sonja
2017-01-01
Purpose: The emergence of tense-morpheme marking during language acquisition is highly variable, which confounds the use of tense marking as a diagnostic indicator of language impairment in linguistically diverse populations. In this study, we seek to better understand tense-marking patterns in young bilingual children by comparing phonological…
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International Business, Gender, and Training: Preparing for the Global Economy.
ERIC Educational Resources Information Center
Hugenberg, Lawrence W.; And Others
This paper deals with how to train employees in transnational companies to be more "global" in their understanding and awareness of different cultures. The paper defines as "target culture" where the employee or his family will be working and considers as a confounding variable in the international marketplace the role to be…
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The Sensitivity of the Right Hemisphere to Contextual Information in Sentences
ERIC Educational Resources Information Center
Gouldthorp, Bethanie; Coney, Jeffrey
2009-01-01
One explanation for the inconsistencies in research examining the sentence comprehension abilities of the right hemisphere (RH) is the presence of confounding variables that have generally served to disadvantage the processing capacities of the RH. As such, the present study aimed to investigate hemispheric differences in the use of message-level…
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Brasic, J R; Barnett, J Y; Kaplan, D; Sheitman, B B; Aisemberg, P; Lafargue, R T; Kowalik, S; Clark, A; Tsaltas, M O; Young, J G
1994-07-01
In an open, nonblind clinical trial, clomipramine reduced adventitious movements and compulsions in five previously medicated prepubertal boys with autistic disorder and severe mental retardation. Poorly adapted rating scales, interrater variability, subject heterogeneity, different treatment histories, and environmental stresses confounded the assessment of treatment effects.
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Gierthmühlen, Janne; Enax-Krumova, Elena K; Attal, Nadine; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Mainka, Tina; Rice, Andrew S C; Segerdahl, Märta; Sindrup, Søren H; Serra, Jordi; Tölle, Thomas; Treede, Rolf-Detlef; Baron, Ralf; Maier, Christoph
2015-11-01
Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.
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Wingenfeld, Katja; Schulz, Michael; Damkroeger, Annika; Philippsen, Christine; Rose, Matthias; Driessen, Martin
2010-09-01
In psychoneuroendocrinology research, salivary measures have become increasingly important. While several studies focus on determinants of salivary cortisol such as age, gender, and gynaecological variables, less research has focused on confounding variables of salivary alpha-amylase (sAA). In a large sample of nurses (N=215) we analyzed the impact of age, gender, intake of oral contraceptives, smoking, coffee consumption as well as psychological parameters, such as work stress and burnout, on basal diurnal sAA release. Saliva was collected at 07:00 h, 11:30 h, 17:30 h, and 20:00 h on a working day during early shift. Only gender could be identified to have an impact on sAA, with females having a more pronounced sAA increase over the course of the day. Whereas depression, anxiety, work stress and burnout were not associated with sAA, a small negative correlation between social difficulties, measured with the Chronic Stress Screening Scale, and sAA could be identified. Copyright (c) 2010 Elsevier B.V. All rights reserved.
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Age at immigration and crime in Stockholm using sibling comparisons.
Beckley, Amber L
2015-09-01
Past Swedish research has shown that immigrants arriving in the receiving country at an older age are less likely to commit crime than immigrants arriving at a younger age. Segmented assimilation theory argues that the family and neighborhood may be important factors affecting how age at immigration and crime are related to one another. This study used population-based register data on foreign-background males from Stockholm to test the effect of age at immigration on crime. Potential confounding from the family and neighborhood was addressed using variables and modeling strategies. Initial results, using variables to control for confounding, showed that people who immigrated around age 4 were the most likely to be suspected of a crime. When controlling for unmeasured family characteristics, it seemed that a later age at immigration was tied to a lower likelihood of crime, which does not corroborate past research findings. The effect of age at immigration, however, was not statistically significant. The results imply that future research on entire families may be a worthwhile endeavor. Copyright © 2015 Elsevier Inc. All rights reserved.
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Portugal, Liana Catarina L; Pereira, Mirtes Garcia; Alves, Rita de Cássia S; Tavares, Gisella; Lobo, Isabela; Rocha-Rego, Vanessa; Marques-Portella, Carla; Mendlowicz, Mauro V; Coutinho, Evandro S; Fiszman, Adriana; Volchan, Eliane; Figueira, Ivan; Oliveira, Letícia de
2012-03-01
Tonic immobility is a defensive reaction occurring under extreme life threats. Patients with posttraumatic stress disorder (PTSD) reporting peritraumatic tonic immobility show the most severe symptoms and a poorer response to treatment. This study investigated the predictive value of tonic immobility for posttraumatic stress symptoms in a non-clinical sample. One hundred and ninety-eight college students exposed to various life threatening events were selected to participate. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and tonic immobility questions were used. Linear regression models were fitted to investigate the association between peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation, peritraumatic panic reactions, negative affect, gender, type of trauma, and time since trauma were considered as confounding variables. We found significant association between peritraumatic tonic immobility and PTSD symptoms in a non-clinical sample exposed to various traumas, even after regression controlled for confounding variables (β = 1.99, p = 0.017). This automatic reaction under extreme life threatening stress, although adaptive for defense, may have pathological consequences as implied by its association with PTSD symptoms.
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Negative psychological aspects and survival in lung cancer patients.
Nakaya, Naoki; Saito-Nakaya, Kumi; Akechi, Tatsuo; Kuriyama, Shinichi; Inagaki, Masatoshi; Kikuchi, Nobutaka; Nagai, Kanji; Tsugane, Shoichiro; Nishiwaki, Yutaka; Tsuji, Ichiro; Uchitomi, Yosuke
2008-05-01
We conducted a prospective cohort study in Japan to investigate associations between negative psychological aspects and cancer survival. Between July 1999 and July 2004, a total of 1178 lung cancer patients were enrolled. The questionnaire asked about socioeconomic variables, smoking status, clinical symptoms, and psychological aspects after diagnosis. Negative psychological aspects were assessed for the subscales of helplessness/hopelessness and depression. Clinical stage, performance status (PS), and histologic type were obtained from medical charts. The subjects were followed up until December 2004, and 686 had died. A Cox regression model was used to estimate the hazards ratio (HR) of all-cause mortality. After adjustment for socioeconomic variables and smoking status in addition to sex, age, and histologic type, both helplessness/hopelessness and depression subscales showed significant linear positive associations with the risk of mortality (p for trend<0.001 for both). However, after adjustment for clinical state variables in addition to sex, age, and histologic type, these significant linear positive associations were no longer observed (p for trend=0.41 and 0.26, respectively). Our data supported the hypothesis that the association between helplessness/hopelessness and depression and the risk of mortality among lung cancer patients was largely confounded by clinical state variables including clinical stage, PS, and clinical symptoms. (c) 2007 John Wiley & Sons, Ltd.
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Burbach, D J; Peterson, L
1986-01-01
Cognitive-developmental studies relevant to children's concepts of physical illness are reviewed and critiqued. Although numerous methodological weaknesses make firm conclusions difficult, most data appear to suggest that children's concepts of illness do evolve in a systematic and predictable sequence consistent with Piaget's theory of cognitive development. Methodological weaknesses identified include poor description of samples, assessment instruments, and procedures; lack of control over potential observer bias, expectancy effects, and other confounding variables; and minimal attention to reliability and validity issues. Increased methodological rigor and a further explication of the specific and unique ways in which children's concepts of illness develop over the course of cognitive development could substantially increase the value of these studies for professionals in pediatric health care settings.
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Neonatal Neurobehavioral and Neuroanatomic Correlates of Prenatal Cocaine Exposure
FRANK, DEBORAH A.; AUGUSTYN, MARILYN; ZUCKERMAN, BARRY S.
2008-01-01
Complex methodologic challenges face researchers studying the effects of prenatal cocaine exposure on infant outcome. These include unavoidable imprecision in ascertaining the gestational timing and dose of cocaine to which the fetus was exposed and difficulties in identifying and quantifying the confounding, mediating, and moderating variables. Review of research on neonatal behavioral and cranial ultrasound findings following in utero cocaine exposure is used to illustrate these issues. We conclude that there are measurable but not dramatic dose-related effects of prenatal cocaine exposure on infant central nervous system structure and function. The effects of dose of prenatal cocaine exposure on later child development remain to be determined. Such research would be facilitated by a scientific consensus delineating relative doses of prenatal cocaine exposure. PMID:9668396
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NASA Technical Reports Server (NTRS)
Seeley, M. W.; Ruschy, D. L.; Linden, D. R.
1983-01-01
A cooperative research project was initiated in 1982 to study differences in thematic mapper spectral characteristics caused by variable tillage and crop residue practices. Initial evaluations of radiometric data suggest that spectral separability of variably tilled soils can be confounded by moisture and weathering effects. Separability of bare tilled soils from those with significant amounts of corn residue is enhanced by wet conditions, but still possible under dry conditions when recent tillage operations have occurred. In addition, thematic mapper data may provide an alternative method to study the radiant energy balance at the soil surface in conjunction with variable tillage systems.
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Domingues, Érica Prado; Silva, Guilherme Gomes; Oliveira, Andrei Barbassa; Mota, Lorrany Marins; Santos, Vanessa Santana Vieira; de Campos, Edimar Olegário; Pereira, Boscolli Barbosa
2018-03-14
Workers in several occupational environments are exposed to pollutants. Street vendors, for example, typically work in a high-traffic urban environment and are exposed to numerous air pollutants, including genotoxic substances emitted by motor vehicles. This study examined the genotoxic effects of exposure to air pollution. We conducted cytological analyses to assess frequencies of micronucleated (MN) and binucleated (BN) cells in a sample of exfoliated oral mucosa cells. We compared street vendors and control subjects in the city of Uberlândia, Minas Gerais, Brazil, and also collected quantitative information on exposure conditions of all test subjects, including concentrations of particulate matter. We found street vendors to exhibit higher frequencies of MN cells compared to the control group. We evaluated the effects of possible confounding variables on MN frequencies, namely the body mass index (BMI), age, as well as smoking and alcohol habits. Multiple linear regression analysis found no significant effects of any of those variables. Our results suggest that continued exposure to air pollution from traffic represents a major source of genotoxicity and raises concerns regarding disease prevention not only in street vendors but also other groups of people working in urban environments.
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The Association of Visual Impairment With Clinical Outcomes in Hemodialysis Patients.
Hong, Yu Ah; Kim, Suk Young; Kim, Su-Hyun; Kim, Young Ok; Jin, Dong Chan; Song, Ho Chul; Choi, Euy Jin; Kim, Yong-Lim; Kim, Yon-Su; Kang, Shin-Wook; Kim, Nam-Ho; Yang, Chul Woo; Kim, Yong Kyun
2016-05-01
Visual impairment limits people's ability to perform daily tasks and affects their quality of life. We evaluated the impact of visual impairment on clinical outcomes in hemodialysis (HD) patients.HD patients were selected from the Clinical Research Center registry a prospective cohort study on dialysis patients in Korea. Visual impairment was defined as difficulty in daily life due to decreased visual acuity or blindness. The primary outcome was all-cause mortality and the secondary outcomes were cardiovascular and infection-related hospitalization.A total of 3250 patients were included. Seven hundred thirty (22.5%) of the enrolled patients had visual impairment. The median follow-up period was 30 months. The Kaplan-Meier curve and log-rank test showed that all-cause mortality rates (P < 0.001) as well as cardiovascular and infection-related hospitalization rates (P < 0.001 and P < 0.001) were significantly higher in patients with visual impairment than in patients without visual impairment. In the multivariable analysis, visual impairment had significant predictive power for all-cause mortality (Hazard ratio [HR], 1.77, 95% confidence interval [CI], 1.21-2.61, P = 0.004) and cardiovascular hospitalization (HR 1.45 [1.00-1.90], P = 0.008) after adjusting for confounding variables. Of these 3250 patients, 634 patients from each group were matched by propensity scores. In the propensity score matched analysis, patients with visual impairment had independently significant associations with increased all-cause mortality (HR 1.69 [1.12-2.54], P = 0.01) and cardiovascular hospitalization (HR 1.48 [1.08-2.02], P = 0.01) compared with patients without visual impairment after adjustment for confounding variables.Our data demonstrated that visual impairment was an independent risk factor for clinical adverse outcomes in HD patients.
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Vickers, Andrew J; Savage, Caroline J; Bianco, Fernando J; Klein, Eric A; Kattan, Michael W; Secin, Fernando P; Guilloneau, Bertrand D; Scardino, Peter T
2011-04-01
Statistical models predicting cancer recurrence after surgery are based on biologic variables. We have shown previously that prostate cancer recurrence is related to both tumor biology and to surgical technique. Here, we evaluate the association between several biological predictors and biochemical recurrence across varying surgical experience. The study included two separate cohorts: 6,091 patients treated by open radical prostatectomy and an independent replication set of 2,298 patients treated laparoscopically. We calculated the odds ratios for biological predictors of biochemical recurrence-stage, Gleason grade and prostate-specific antigen (PSA)-and also the predictive accuracy (area under the curve, AUC) of a multivariable model, for subgroups of patients defined by the experience of their surgeon. In the open cohort, the odds ratio for Gleason score 8+ and advanced pathologic stage, though not PSA or Gleason score 7, increased dramatically when patients treated by surgeons with lower levels of experience were excluded (Gleason 8+: odds ratios 5.6 overall vs. 13.0 for patients treated by surgeons with 1,000+ prior cases; locally advanced disease: odds ratios of 6.6 vs. 12.2, respectively). The AUC of the multivariable model was 0.750 for patients treated by surgeons with 50 or fewer cases compared to 0.849 for patients treated by surgeons with 500 or more. Although predictiveness was lower overall for the independent replication set cohort, the main findings were replicated. Surgery confounds biology. Although our findings have no direct clinical implications, studies investigating biological variables as predictors of outcome after curative resection of cancer should consider the impact of surgeon-specific factors. Copyright © 2010 UICC.
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Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.
Plessinger, M A
1998-03-01
Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and the effects of amphetamine and methamphetamine in general.
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Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.
2014-01-01
Background Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results Included were 7688 participants of the PREVEND Study, an observational, general population‐based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100−fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross‐sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both P<0.001). Albuminuria was found to be associated positively with tubular uric acid reabsorption, again both crude and after adjustment for potential confounders (both P<0.001). In longitudinal analyses during a median follow‐up of 10.5 years, 702 cardiovascular events occurred. After adjusting for cardiovascular risk factors, both albuminuria and serum uric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], P<0.001, respectively). A significant interaction between these variables was present (P<0.001), consistent with high serum uric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa. Conclusions Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome. PMID:24772520
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Lisboa, Renato; Chun, Yeoun Sook; Zangwill, Linda M.; Weinreb, Robert N.; Rosen, Peter N.; Liebmann, Jeffrey M.; Girkin, Christopher A.; Medeiros, Felipe A.
2013-01-01
Objective To evaluate the relationship between binocular rates of visual field change and vision-related quality of life (VRQOL) in glaucoma. Methods The study included 796 eyes of 398 participants that had diagnosed or suspected glaucoma followed for an average of 7.3 ± 2.0 years. Subjects were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). VRQOL was evaluated using the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at the last follow-up visit. Integrated binocular visual fields (BVF) were calculated from the monocular fields of each patient. Linear regression of mean deviation (MD) values was used to evaluate rates of visual field change during the follow-up period. Logistic regression models were used to investigate the relationship between abnormal VRQOL and rates of visual field change, while adjusting for potentially confounding socio-economic and demographic variables. Results Thirty-two patients (8.0%) had abnormal VRQOL as determined by the results of the NEI VFQ-25 questionnaire. Subjects with abnormal VRQOL had significantly faster rates of BVF change than those with normal VRQOL (−0.18 db/year vs. −0.06 dB/year, respectively; P < 0.001). Rates of BVF change were significantly associated with abnormality in VRQOL (OR = 1.31 per 0.1dB/year faster; P = 0.038), after adjustment for confounding variables. Conclusions Patients with faster rates of BVF change were at higher risk of reporting abnormal VRQOL. Assessment of rates of BVF change may provide useful information in determining risk of functional impairment in glaucoma. PMID:23450425
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2013-01-01
Background The current experiment investigated the impact of two potential confounding variables on the postural balance in young participants: the induced-experimental activity prior to the static postural measurements and the well-documented time-of-day effects. We mainly hypothesized that an exhaustive exercise and a high attention-demanding task should result in alterations of postural control. Methods Ten participants performed three experimental sessions (differentiated by the activity – none, cognitive or physical – prior of the assessment of postural stability), separated by one day at least. Each session included postural balance assessments around 8 a.m., 12.00 p.m. and 5 p.m. ± 30 min. The physical and cognitive activities were performed only before the 12 o’clock assessment. The postural tests consisted of four conditions of quiet stance: stance on a firm surface with eyes open; stance on a firm surface with eyes closed; stance on a foam surface with eyes open and stance on a foam surface with eyes closed. Postural performance was assessed by various center of pressure (COP) parameters. Results Overall, the COP findings indicated activity-related postural impairment, with an increase in body sway in the most difficult conditions (with foam surface), especially when postural measurements are recorded just after the running exercise (physical session) or the psychomotor vigilance test (cognitive session). Conclusions Even if no specific influence of time-of-day on static postural control is demonstrated, our results clearly suggest that the activities prior to balance tests could be a potential confounding variable to be taken into account and controlled when assessing clinical postural balance. PMID:23452958
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Doughty, Michael J; Blades, Kenneth A; Ibrahim, Nassim
2002-03-01
The goal of this study was both to assess the frequency of self-reported eye symptoms for employees in a non-air-conditioned office building complex, and to specifically assess whether confounding variables (contact lens wear, medicines use, and provoking stimuli) had a discernible impact on the characteristics of this reporting. A questionnaire was distributed, in the winter months, to office employees in a building complex within a city-located University site, consisting of non-air-conditioned rooms with some mechanical ventilation. The questionnaire asked respondents to identify any eye symptoms experienced (foreign body sensation, soreness, dryness, grittiness, itchiness, stinging, intense burning), the frequency of their occurrence, details of any conditions provoking eye symptoms (such as changes in the microenvironment), their medication use and if they were contact lens wearers. The proportion of respondents for various categories was calculated, along with the total number of symptoms. If 'eye irritation' is considered as reporting any symptoms experienced at any time, then 63% of 292 respondents (median age 42.5 years) reported an average of 1.83 symptoms. However, the identification of contact lens wearers, medication use (especially for seasonal allergies) and provoking stimuli reduced this prevalence to just 29% (with the average number of symptoms being 1.51). If the frequency of experiencing symptoms was also taken into account (never, sometimes, often, and constantly), then only 12.3% of the respondents indicated symptoms often or constantly, i.e. could be considered to have significant symptoms. In all categories, men were more likely to report eye symptoms compared with women. The results confirm that office employees are likely to have some ocular symptoms, but that even a simple consideration of possible confounding variables can greatly change the reported prevalence of eye irritation that might be specifically associated with the workplace environment.
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Differential expression analysis for RNAseq using Poisson mixed models
Sun, Shiquan; Hood, Michelle; Scott, Laura; Peng, Qinke; Mukherjee, Sayan; Tung, Jenny
2017-01-01
Abstract Identifying differentially expressed (DE) genes from RNA sequencing (RNAseq) studies is among the most common analyses in genomics. However, RNAseq DE analysis presents several statistical and computational challenges, including over-dispersed read counts and, in some settings, sample non-independence. Previous count-based methods rely on simple hierarchical Poisson models (e.g. negative binomial) to model independent over-dispersion, but do not account for sample non-independence due to relatedness, population structure and/or hidden confounders. Here, we present a Poisson mixed model with two random effects terms that account for both independent over-dispersion and sample non-independence. We also develop a scalable sampling-based inference algorithm using a latent variable representation of the Poisson distribution. With simulations, we show that our method properly controls for type I error and is generally more powerful than other widely used approaches, except in small samples (n <15) with other unfavorable properties (e.g. small effect sizes). We also apply our method to three real datasets that contain related individuals, population stratification or hidden confounders. Our results show that our method increases power in all three data compared to other approaches, though the power gain is smallest in the smallest sample (n = 6). Our method is implemented in MACAU, freely available at www.xzlab.org/software.html. PMID:28369632
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Becker, Betsy Jane; Aloe, Ariel M; Duvendack, Maren; Stanley, T D; Valentine, Jeffrey C; Fretheim, Atle; Tugwell, Peter
2017-09-01
To outline issues of importance to analytic approaches to the synthesis of quasi-experiments (QEs) and to provide a statistical model for use in analysis. We drew on studies of statistics, epidemiology, and social-science methodology to outline methods for synthesis of QE studies. The design and conduct of QEs, effect sizes from QEs, and moderator variables for the analysis of those effect sizes were discussed. Biases, confounding, design complexities, and comparisons across designs offer serious challenges to syntheses of QEs. Key components of meta-analyses of QEs were identified, including the aspects of QE study design to be coded and analyzed. Of utmost importance are the design and statistical controls implemented in the QEs. Such controls and any potential sources of bias and confounding must be modeled in analyses, along with aspects of the interventions and populations studied. Because of such controls, effect sizes from QEs are more complex than those from randomized experiments. A statistical meta-regression model that incorporates important features of the QEs under review was presented. Meta-analyses of QEs provide particular challenges, but thorough coding of intervention characteristics and study methods, along with careful analysis, should allow for sound inferences. Copyright © 2017 Elsevier Inc. All rights reserved.
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Specific Impairments in the Recognition of Emotional Facial Expressions in Parkinson’s Disease
Clark, Uraina S.; Neargarder, Sandy; Cronin-Golomb, Alice
2008-01-01
Studies investigating the ability to recognize emotional facial expressions in non-demented individuals with Parkinson’s disease (PD) have yielded equivocal findings. A possible reason for this variability may lie in the confounding of emotion recognition with cognitive task requirements, a confound arising from the lack of a control condition using non-emotional stimuli. The present study examined emotional facial expression recognition abilities in 20 non-demented patients with PD and 23 control participants relative to their performances on a non-emotional landscape categorization test with comparable task requirements. We found that PD participants were normal on the control task but exhibited selective impairments in the recognition of facial emotion, specifically for anger (driven by those with right hemisphere pathology) and surprise (driven by those with left hemisphere pathology), even when controlling for depression level. Male but not female PD participants further displayed specific deficits in the recognition of fearful expressions. We suggest that the neural substrates that may subserve these impairments include the ventral striatum, amygdala, and prefrontal cortices. Finally, we observed that in PD participants, deficiencies in facial emotion recognition correlated with higher levels of interpersonal distress, which calls attention to the significant psychosocial impact that facial emotion recognition impairments may have on individuals with PD. PMID:18485422
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Racial and ethnic differences in utilization of mental health services among high-risk youths.
Garland, Ann F; Lau, Anna S; Yeh, May; McCabe, Kristen M; Hough, Richard L; Landsverk, John A
2005-07-01
Racial and ethnic disparities in mental health service use have been identified as a major public health problem. However, the extent to which these disparities may be accounted for by other confounding sociodemographic or clinical predictors of service use (e.g., family income, functional impairment, caregiver strain) is relatively unexplored, especially for youth services. The goal of this study was to test for racial/ethnic disparities in use of a variety of outpatient, inpatient, and informal mental health services among high-risk youths, with the effects of other predictive factors controlled. Participants were 1,256 youths ages 6-18 years who received services in a large, publicly funded system of care (including the child welfare, juvenile justice, special education, alcohol and drug abuse, and mental health service sectors). Youths and caregivers were interviewed with established measures of mental health service use, psychiatric diagnoses, functional impairment, caregiver strain, and parental depression. Significant racial/ethnic group differences in likelihood of receiving any mental health service and, specifically, formal outpatient services were found after the effects of potentially confounding variables were controlled. Race/ethnicity did not exert a significant effect on the use of informal or 24-hour-care services. Racial/ethnic disparities in service use remain a public health problem.
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Bárbara Pereira Costa, Aline; Andrade Carneiro Machado, Luciana; Marcos Domingues Dias, João; Keller Coelho de Oliveira, Adriana; Ude Viana, Joana; da Silva, Sílvia Lanziotti Azevedo; Gonçalves Pereira Couto, Flávia; Lustosa Torres, Juliana; Mendes, Liliane P; Correa Dias, Rosangela
2016-01-01
Malnutrition is a risk factor for noncommunicable diseases related to ageing, and it can also contribute to musculoskeletal health. This study investigated whether nutritional risk is associated with chronic musculoskeletal pain in community-dwelling older persons. Nutritional risk was assessed by the DETERMINE Checklist. Chronic musculoskeletal pain was defined as the presence of pain in the past six months that did not disappear for at least 30 consecutive days. Multivariate logistic regression including confounding variables was used for the analysis. The sample was comprised of 383 participants (age 75.6 ± SD 6.1); the majority were at moderate-to-high nutritional risk (69%) and approximately one third presented chronic musculoskeletal pain (30%). The nutritional risk score was independently associated with chronic musculoskeletal pain: adding one unit in the risk score produces an 11% increment in the odds of presenting pain (OR 1.109, 95% CI 1.022-1.204). Individuals classified into moderate- or high-risk categories also had substantially higher odds (∼90%) of presenting chronic musculoskeletal pain when compared to those in the low-risk category, although our findings were only marginally significant. This is the first study to demonstrate the association between nutritional risk and chronic musculoskeletal pain above and beyond the contributed effects from relevant confounders.
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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.
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Adolescent Support Seeking as a Path to Adult Functional Independence
Szwedo, David E.; Hessel, Elenda T.; Loeb, Emily L.; Hafen, Christopher A.; Allen, Joseph P.
2017-01-01
The potential importance of depending on others during adolescence in order to establish independence in young adulthood was examined across adolescence to emerging adulthood. Participants included 184 teens (46% male; 42% non-White), their mothers, best friends, and romantic partners, assessed at ages 13–14, 18, 21–22, and 25. Path analyses showed that associations were both partner and age specific: markers of independence were predicted by participants’ efforts to seek support from mothers at age 13, best friends at 18, and romantic partners at 21. Importantly, analyses controlled for support seeking from these partners at other ages, as well as for other potentially confounding variables including attachment security, scholastic/job competence, and physical attractiveness over time. Moreover, analyses suggested the transfer of support seeking behavior from mothers to best friends to romantic partners over time based on support given by the previous partner at an earlier age. PMID:28358534
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Frailty among rural elderly adults
2014-01-01
Background This study aimed to estimate the prevalence and associated factors related to frailty, by Fried criteria, in the elderly population in a rural area in the Andes Mountains, and to analyze the relationship of these with comorbidity and disability. Methods A cross-sectional study was undertaken involving 1878 participants 60 years of age and older. The frailty syndrome was diagnosed based on the Fried criteria (weakness, low speed, low physical activity, exhaustion, and weight loss). Variables were grouped as theoretical domains and, along with other potential confounders, were placed into five categories: (a) demographic and socioeconomic status, (b) health status, (c) self-reported functional status, (d) physical performance-based measures, and (e) psychosocial factors. Chi-square, ANOVA, and multinomial logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest. Results The prevalence of frailty was 12.2%. Factors associated with frailty were age, gender, health status variables that included self-perceived health and number of chronic conditions, functional covariate variables that included disability in activities in daily living (ADL), disabilities in instrumental ADL, chair stand time, and psychosocial variables that included depressive symptoms and cognitive impairment. Higher comorbidity and disability was found in frail elderly people. Only a subset of frail elderly people (10%) reported no disease or disability. Conclusions A relevant number of elderly persons living in rural areas in the Andes Mountains are frail. The prevalence of frailty is similar to that reported in other populations in the Latin American region. Our results support the use of modified Cardiovascular Health Study criteria to measure frailty in communities other than urban settings. Frailty in this study was strongly associated with comorbidities, and frailty and comorbidity predicted disability. PMID:24405584
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Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn
2016-11-01
It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up. © 2016 The British Psychological Society.
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Haslam, N; Holland, E; Kuppens, P
2012-05-01
Taxometric research methods were developed by Paul Meehl and colleagues to distinguish between categorical and dimensional models of latent variables. We have conducted a comprehensive review of published taxometric research that included 177 articles, 311 distinct findings and a combined sample of 533 377 participants. Multilevel logistic regression analyses have examined the methodological and substantive variables associated with taxonic (categorical) findings. Although 38.9% of findings were taxonic, these findings were much less frequent in more recent and methodologically stronger studies, and in those reporting comparative fit indices based on simulated comparison data. When these and other possible confounds were statistically controlled, the true prevalence of taxonic findings was estimated at 14%. The domains of normal personality, mood disorders, anxiety disorders, eating disorders, externalizing disorders, and personality disorders (PDs) other than schizotypal yielded little persuasive evidence of taxa. Promising but still not definitive evidence of psychological taxa was confined to the domains of schizotypy, substance use disorders and autism. This review indicates that most latent variables of interest to psychiatrists and personality and clinical psychologists are dimensional, and that many influential taxonic findings of early taxometric research are likely to be spurious.
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Rodríguez-Colón, Sol M.; He, Fan; Bixler, Edward O.; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N.; Calhoun, Susan; Zheng, Zhi-Jie; Liao, Duanping
2015-01-01
Objective To investigate the effects of objectively measured habitual sleep patterns on cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods We used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. CAM was assessed by heart rate (HR) variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-h electrocardiogram, on a 30-min basis. The HRV indices included frequency domain (HF, LF, and LF/HF ratio), and time domain (SDNN, RMSSD, and heart rate or HR) variables. Actigraphy was used for seven consecutive nights to estimate nightly sleep duration and time in bed. The seven-night mean (SD) of sleep duration and sleep efficiency were used to represent sleep duration, duration variability, sleep efficiency, and efficiency variability, respectively. HF and LF were log-transformed for statistical analysis. Linear mixed-effect models were used to analyze the association between sleep patterns and CAM. Results After adjusting for major confounders, increased sleep duration variability and efficiency variability were significantly associated with lower HRV and higher HR during the 39-h, as well as separated by daytime and nighttime. For instance, a 1-h increase in sleep duration variability is associated with −0.14(0.04), −0.12(0.06), and −0.16(0.05) ms2 decrease in total, daytime, and nighttime HF, respectively. No associations were found between sleep duration, or sleep efficiency and HRV. Conclusion Higher habitual sleep duration variability and efficiency variability are associated with lower HRV and higher HR, suggesting that an irregular sleep pattern has an adverse impact on CAM, even in healthy adolescents. PMID:25555635
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Khan, Jenna; Lieberman, Joshua A; Lockwood, Christina M
2017-05-01
microRNAs (miRNAs) hold promise as biomarkers for a variety of disease processes and for determining cell differentiation. These short RNA species are robust, survive harsh treatment and storage conditions and may be extracted from blood and tissue. Pre-analytical variables are critical confounders in the analysis of miRNAs: we elucidate these and identify best practices for minimizing sample variation in blood and tissue specimens. Pre-analytical variables addressed include patient-intrinsic variation, time and temperature from sample collection to storage or processing, processing methods, contamination by cells and blood components, RNA extraction method, normalization, and storage time/conditions. For circulating miRNAs, hemolysis and blood cell contamination significantly affect profiles; samples should be processed within 2 h of collection; ethylene diamine tetraacetic acid (EDTA) is preferred while heparin should be avoided; samples should be "double spun" or filtered; room temperature or 4 °C storage for up to 24 h is preferred; miRNAs are stable for at least 1 year at -20 °C or -80 °C. For tissue-based analysis, warm ischemic time should be <1 h; cold ischemic time (4 °C) <24 h; common fixative used for all specimens; formalin fix up to 72 h prior to processing; enrich for cells of interest; validate candidate biomarkers with in situ visualization. Most importantly, all specimen types should have standard and common workflows with careful documentation of relevant pre-analytical variables.
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To Cull or Not To Cull? Considerations for Studies of Endocrine-Disrupting Chemicals.
Suvorov, Alexander; Vandenberg, Laura N
2016-07-01
The power of animal models is derived from the ability to control experimental variables so that observed effects may be unequivocally attributed to the factor that was changed. One variable that is difficult to control in animal experiments is the number and composition of offspring in a litter. To account for this variability, artificial equalization of the number of offspring in a litter (culling) is often used. The rationale for culling, however, has always been controversial. The Developmental Origins of Health and Disease concept provides a new context to evaluate the pros and cons of culling in laboratory animal studies, especially in the context of endocrine-disrupting chemicals. Emerging evidence indicates that culling, especially of large litters, can drastically change the feeding status of a pup, which can result in compensatory growth with long-term consequences for the animal, including increased risk of cardio-metabolic diseases. Similarly, culling of litters to intentionally bias sex ratios can alter the animal's behavior and physiology, with effects observed on a wide range of outcomes. Thus, in an attempt to control for variability in developmental rates, culling introduces an uncontrolled or confounding variable, which itself may affect a broad spectrum of health-related consequences. Variabilities in culling protocols could be responsible for differences in responses to endocrine-disrupting chemicals reported across studies. Because litter sex composition and size are vectors that can influence both prenatal and postnatal growth, they are essential considerations for the interpretation of results from laboratory animal studies.
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Prenatal Maternal Stress Associated with ADHD and Autistic Traits in early Childhood
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
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Prenatal, perinatal, and adolescent exposure to marijuana: Relationships with aggressive behavior.
Barthelemy, Olivier J; Richardson, Mark A; Cabral, Howard J; Frank, Deborah A
This manuscript reviews research exploring the relationship between prenatal, perinatal, and adolescent exposure to marijuana and aggressive behavior, including physical aggression. Areas of inquiry include animal research, as well as human research, on prenatal exposure and on marijuana use during adolescence. Potential psychosocial and psychopharmacological mechanisms are identified, as well as relevant confounds. The prenatal marijuana exposure literature provides minimal support for a direct relationship with aggressive behavior in childhood. The adolescent use literature suggests a marginal (at best) association between acute intoxication and aggressive behavior, and an association between chronic use and aggressive behavior heavily influenced by demographic variables, rather than direct, psychopharmacological mechanisms. Cannabis withdrawal symptoms also may include aggression and anger, but there is little evidence to suggest that these effects are large or specific to withdrawal from marijuana compared to other substances. This review will offer recommendations for clinical care and public policy, as well as important questions for future research. Copyright © 2016 Elsevier Inc. All rights reserved.
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ERIC Educational Resources Information Center
An, Brian P.; Loes, Chad N.; Trolian, Teniell L.
2017-01-01
Using longitudinal data from multiple institutions, we focused on the relation between binge drinking and academic performance. Binge drinking exerts a negative influence on grade point average, even after accounting for a host of precollege confounding variables. Furthermore, the number of times a student binge drinks in college is less…
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Root disease and other unforeseen variables that confound restoration efforts
William J. Otrosina; Shi-Jean S. Sung; Stanley J. Zarnoch; Brian T. Sullivan; Charles H. Walkinshaw
2002-01-01
Unanticipated disease problems thwarting restoration efforts can emerge in forest ecosystems. An example is the longleaf pine (Pinus palustris Mill.) ecosystem. This species once occupied nearly 30 million ha but now its range is reduced to approximately 1.5 million ha. Restoring longleaf pine to many sites in its former range is an important goal...
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Gender Bias in the Diagnosis of a Geriatric Standardized Patient: A Potential Confounding Variable
ERIC Educational Resources Information Center
Lewis, Roya; Lamdan, Ruth M.; Wald, David; Curtis, Michael
2006-01-01
Background: Gender bias has been reported in the diagnosis and treatment of patients with a variety of illnesses. In the context of our 10-station fourth year Objective Structured Clinical Evaluation, we queried whether this could influence diagnosis in a geriatric case. Case writers hypothesized that, due to this bias, the female standardized…
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Typing Speed as a Confounding Variable and the Measurement of Quality in Divergent Thinking
ERIC Educational Resources Information Center
Forthmann, Boris; Holling, Heinz; Çelik, Pinar; Storme, Martin; Lubart, Todd
2017-01-01
The need to control for writing or typing speed when assessing divergent-thinking performance has been recognized since the early '90s. An even longer tradition in divergent-thinking research has the issue of scoring the responses for quality. This research addressed both issues within structural equation modeling. Three dimensions of…
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Chao, Linda L; Abadjian, Linda R; Esparza, Iva L; Reeb, Rosemary
2016-09-01
Despite the fact that sleep disturbances are common in veterans with Gulf War Illness (GWI), there has been a paucity of published sleep studies in this veteran population to date. Therefore, the present study examined subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia severity (assessed with the Insomnia Severity Index), and risk for obstructive sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans. Veterans with GWI, defined either by the Kansas or Centers for Disease Control and Prevention criteria, had greater risk for obstructive sleep apnea (i.e., higher STOP scores) than veterans without GWI. This difference persisted even after accounting for potentially confounding demographic (e.g., age, gender) and clinical variables. Veterans with GWI, defined by either the Kansas or Centers for Disease Control and Prevention criteria, also had significantly greater insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05), even after accounting for potentially confounding variables. Furthermore, there were significant, positive correlations between insomnia severity, subjective sleep quality, and GWI symptom severity (p ≤ 0.01). In stepwise linear regression models, insomnia severity significantly predicted GWI status over and above demographic and clinical variables. Together these findings provide good rationale for treating sleep disturbances in the management of GWI. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.
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Coping strategies and quality of life in caregivers of dependent elderly relatives.
Rodríguez-Pérez, Margarita; Abreu-Sánchez, Ana; Rojas-Ocaña, María Jesús; Del-Pino-Casado, Rafael
2017-04-14
Despite the importance of coping in caregiving, there are few studies on the relationship between coping and quality of life in caregivers of the frail dependent elderly. Thus, this study aims to analyze the relationship between coping strategies and quality of life dimensions in primary caregivers of dependent elderly relatives. A cross-sectional study was conducted from 86 caregivers. Predictive variables were coping strategies (problem-focused, emotion-focused, socially-supported, and dysfunctional); dependent variables were quality of life dimensions (psychological, physical, relational, and environmental); and potential confounding variables were age, gender, perceived health and burden of caregiver, and functional capacity of care receiver. Correlation coefficients were calculated and multiple linear regression analysis was performed. After controlling for potential confounders, dysfunctional coping was related to worse quality of life in the psychological dimension, while emotion-focused and socially-supported coping were related to superior psychological and environmental dimensions of quality of life. The physical and relational dimensions of quality of life were not related to coping strategies. 1) it is important to consider coping strategies in the assessment of primary caregivers of dependent elderly relatives; 2) the quality of life of caregivers is related to their coping strategies, 3) their quality of life can be worsened by avoidance-type coping, and 4) their quality of life can be improved by active emotion-focused coping and socially-supported coping.
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Complex Causal Process Diagrams for Analyzing the Health Impacts of Policy Interventions
Joffe, Michael; Mindell, Jennifer
2006-01-01
Causal diagrams are rigorous tools for controlling confounding. They also can be used to describe complex causal systems, which is done routinely in communicable disease epidemiology. The use of change diagrams has advantages over static diagrams, because change diagrams are more tractable, relate better to interventions, and have clearer interpretations. Causal diagrams are a useful basis for modeling. They make assumptions explicit, provide a framework for analysis, generate testable predictions, explore the effects of interventions, and identify data gaps. Causal diagrams can be used to integrate different types of information and to facilitate communication both among public health experts and between public health experts and experts in other fields. Causal diagrams allow the use of instrumental variables, which can help control confounding and reverse causation. PMID:16449586
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Relationship of suicide rates with climate and economic variables in Europe during 2000-2012.
Fountoulakis, Konstantinos N; Chatzikosta, Isaia; Pastiadis, Konstantinos; Zanis, Prodromos; Kawohl, Wolfram; Kerkhof, Ad J F M; Navickas, Alvydas; Höschl, Cyril; Lecic-Tosevski, Dusica; Sorel, Eliot; Rancans, Elmars; Palova, Eva; Juckel, Georg; Isacsson, Goran; Jagodic, Helena Korosec; Botezat-Antonescu, Ileana; Rybakowski, Janusz; Azorin, Jean Michel; Cookson, John; Waddington, John; Pregelj, Peter; Demyttenaere, Koen; Hranov, Luchezar G; Stevovic, Lidija Injac; Pezawas, Lucas; Adida, Marc; Figuera, Maria Luisa; Jakovljević, Miro; Vichi, Monica; Perugi, Giulio; Andreassen, Ole A; Vukovic, Olivera; Mavrogiorgou, Paraskevi; Varnik, Peeter; Dome, Peter; Winkler, Petr; Salokangas, Raimo K R; From, Tiina; Danileviciute, Vita; Gonda, Xenia; Rihmer, Zoltan; Forsman, Jonas; Grady, Anne; Hyphantis, Thomas; Dieset, Ingrid; Soendergaard, Susan; Pompili, Maurizio; Bech, Per
2016-01-01
It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. Data from 29 European countries covering the years 2000-2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north-east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.
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Adolescent sleep disturbance and school performance: the confounding variable of socioeconomics.
Pagel, James F; Forister, Natalie; Kwiatkowki, Carol
2007-02-15
To assess how selected socioeconomic variables known to affect school performance alter the association between reported sleep disturbance and poor school performance in a contiguous middle school/high school population. A school district/college IRB approved questionnaire was distributed in science and health classes in middle school and high school. This questionnaire included a frequency scaled pediatric sleep disturbance questionnaire for completion by students and a permission and demographic questionnaire for completion by parents (completed questionnaires n = 238 with 69.3% including GPA). Sleep complaints occur at high frequency in this sample (sleep onset insomnia 60% > 1 x /wk.; 21.2% every night; sleepiness during the day (45.7% > 1 x /wk.; 15.2 % every night), and difficulty concentrating (54.6% > 1 x /wk.; 12.9% always). Students with lower grade point averages (GPAs) were more likely to have restless/aching legs when trying to fall asleep, difficulty concentrating during the day, snoring every night, difficulty waking in the morning, sleepiness during the day, and falling asleep in class. Lower reported GPAs were significantly associated with lower household incomes. After statistically controlling for income, restless legs, sleepiness during the day, and difficulty with concentration continued to significantly affect school performance. This study provides additional evidence indicating that sleep disturbances occur at high frequencies in adolescents and significantly affect daytime performance, as measured by GPA. The socioeconomic variable of household income also significantly affects GPA. After statistically controlling for age and household income, the number and type of sleep variables noted to significantly affect GPA are altered but persistent in demonstrating significant effects on school performance.
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Vandasova, Zdenka; Vencálek, Ondřej; Puklová, Vladimíra
2016-01-01
Noise is one of the most extensive environmental factors affecting the general population. The present study is focused on the association between discomfort caused by noise and the incidence of certain diseases (ischaemic heart disease, stroke and hypertension). This cross-sectional questionnaire study, conducted in 10 cities in the Czech Republic, comprises two stages with 3592 obtained questionnaires in the first phase and 762 in the second phase. Twelve variables describe subjective responses to noise from different sources at different times of day. The intensity of the associations between variables was measured by correlation coefficient. Logistic regression was used for fitting models of morbidity, and confounders such as age and socio-economic status were included. The hypotheses from the first phase were independently validated using data from the second phase. The general rates of noise annoyance/sleep disturbance had greater correlation with traffic noise variables than with neighbourhood noise variables. Factors significantly associated with diseases are: for hypertension - annoyance by traffic noise (the elderly, odds ratio (OR) 1.4) and sleep disturbance by traffic and neighbourhood noise (the elderly, OR 1.6); for ischaemic heart disease - the general rate of noise annoyance (all respondents, OR 1.5 and the adults 30-60 years, OR 1.8) and the general rate of annoyance and sleep disturbance (all respondents, OR 1.3); for stroke - annoyance and sleep disturbance by traffic and neighbourhood noise (all respondents, OR 1.8). Factors that include multiple sources of noise or non-specific noise are associated with the studied diseases more frequently than the source-specific factors.
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MacInnis, Martin J; McGlory, Chris; Gibala, Martin J; Phillips, Stuart M
2017-06-01
Direct sampling of human skeletal muscle using the needle biopsy technique can facilitate insight into the biochemical and histological responses resulting from changes in exercise or feeding. However, the muscle biopsy procedure is invasive, and analyses are often expensive, which places pragmatic restraints on sample sizes. The unilateral exercise model can serve to increase statistical power and reduce the time and cost of a study. With this approach, 2 limbs of a participant are randomized to 1 of 2 treatments that can be applied almost concurrently or sequentially depending on the nature of the intervention. Similar to a typical repeated measures design, comparisons are made within participants, which increases statistical power by reducing the amount of between-person variability. A washout period is often unnecessary, reducing the time needed to complete the experiment and the influence of potential confounding variables such as habitual diet, activity, and sleep. Variations of the unilateral exercise model have been employed to investigate the influence of exercise, diet, and the interaction between the 2, on a wide range of variables including mitochondrial content, capillary density, and skeletal muscle hypertrophy. Like any model, unilateral exercise has some limitations: it cannot be used to study variables that potentially transfer across limbs, and it is generally limited to exercises that can be performed in pairs of treatments. Where appropriate, however, the unilateral exercise model can yield robust, well-controlled investigations of skeletal muscle responses to a wide range of interventions and conditions including exercise, dietary manipulation, and disuse or immobilization.
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Capacity for Physical Activity Predicts Weight Loss After Roux-en-Y Gastric Bypass
Hatoum, Ida J.; Stein, Heather K.; Merrifield, Benjamin F.; Kaplan, Lee M.
2014-01-01
Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for univariate analysis, 9 with univariate P values ≤ 0.15 were entered into a multivariable regression analysis. Using backward selection, covariates with P < 0.05 were retained. Potential confounders were added back into the model and assessed for effect on all model variables. Complete records were available for 246 of the 300 patients (82%). The patient characteristics were 75% female, 93% white, mean age of 45 years, and mean initial BMI of 52.3 kg/m2. One year after surgery, patients lost an average of 64.8% of their excess weight (s.d. = 20.5%). The multivariable regression analysis revealed that limited physical activity, higher initial BMI, lower educational level, diabetes, and decreased attendance at postoperative appointments had an adverse effect on weight loss after RYGB. A model including these five factors accounts for 41% of the observed variability in weight loss (adjusted r2 = 0.41). In this cohort, higher initial BMI and limited physical activity were the strongest predictors of decreased excess weight loss following RYGB. Limited physical activity may be particularly important because it represents an opportunity for potentially meaningful pre- and postsurgical intervention to maximize weight loss following RYGB. PMID:18997674
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Aschengrau, Ann; Janulewicz, Patricia A; White, Roberta F; Vieira, Veronica M; Gallagher, Lisa G; Getz, Kelly D; Webster, Thomas F; Ozonoff, David M
2016-01-01
Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical nature of the exposure assessments. The Cape Cod Health Study demonstrates how scientists can take advantage of unique "natural experiments" to learn about the health effects of environmental pollution. This body of work has improved our understanding of the long-term health effects of early-life exposure to this common environmental contaminant and will help risk assessors and policymakers ensure that drinking water supplies in the United States are safe for vulnerable populations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Metabolic syndrome and shift work: a systematic review.
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.
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Stürmer, Til; Wyss, Richard; Glynn, Robert J.; Brookhart, M. Alan
2014-01-01
Treatment effects, especially when comparing two or more therapeutic alternatives as in comparative effectiveness research, are likely to be heterogeneous across age, gender, co-morbidities, and co-medications. Propensity scores (PSs), an alternative to multivariable outcome models to control for measured confounding, have specific advantages in the presence of heterogeneous treatment effects. Implementing PSs using matching or weighting allows us to estimate different overall treatment effects in differently defined populations. Heterogeneous treatment effects can also be due to unmeasured confounding concentrated in those treated contrary to prediction. Sensitivity analyses based on PSs can help to assess such unmeasured confounding. PSs should be considered a primary or secondary analytic strategy in non-experimental medical research, including pharmacoepidemiology and non-experimental comparative effectiveness research. PMID:24520806
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Solomon, Daniel H; Shadick, Nancy A; Weinblatt, Michael E; Zak, Agnes; Frits, Michelle; Franklin, Jessica M
2017-06-13
Patient registry data serves an increasing role in drug safety and comparative effectiveness research, but registry databases often do not contain confounder information measured at the same time that treatments begin. This study evaluated a set of approaches for estimating confounder values at treatment initiation using actual data from a rheumatoid arthritis (RA) registry to examine the risk of infection associated with different biologic DMARDs (bDMARDs). We examined the risk of infection associated with starting a TNF inhibitor (TNFi) versus any of the other non-TNFi bDMARDs. Different confounder assessment approaches were tested. All approaches were tested in Cox proportional hazard regression models that used a propensity score (PS). The confounder of interest was the disease activity score (DAS28-CRP). The confounder assessment approaches utilized different temporal relationships between the DAS28-CRP measurement and the start of the treatments of interest. We included 219 subjects with RA with 269 initiations of either a TNFi or a different bDMARD or both. Among this group, 305 infections were reported and confirmed through chart review. The hazard ratio (HR) for the risk of infection associated with use of a non-TNFi bDMARD ranged from 1.17 to 3.03 using 13 different approaches; only the approach with the highest HR produced results significantly different than one, but this approach included the fewest subjects and infections. The relative risk of infection for TNFi and other non-TNFi bDMARDs was similar using various approaches regarding which DAS28-CRP score should be used as the baseline measure in adjusted analyses.
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The Association Between School Bonding and Smoking Amongst Chilean Adolescents.
Gaete, Jorge; Montgomery, Alan; Araya, Ricardo
2015-01-01
The objective of the research was to study the association between school bonding dimensions (school commitment and school attachment) and current adolescent smoking in Chile, controlling for confounding variables using the fifth Chilean School Population National Substance Use Survey, 2003 (CHSS-2003) data set. The CHSS-2003 is a stratified cross-sectional survey that gathers information about personal, familial, peer, and school factors and cigarette use using a self-reported questionnaire. Complete data from 21,956 adolescent students for all the variables of interest were used in the analyses. An exploratory factor analysis (EFA) was performed in order to explore the construct validity of the questionnaire and create the main exposure and potential confounding variables. Multivariable logistic regression analyses were undertaken to study the association between school bonding and smoking. The construct validity of the school attachment and school commitment scales was mainly supported by the EFA. Multivariable analyses showed strong evidence that, after adjusting for factors from different domains, school commitment (student's good grades and school attendance) appears to have a clear inverse association with current smoking (odds ratio [OR]=0.46, 95% confidence interval [CI]: 0.38-0.56). On the other hand, school attachment (their feelings towards their school and their teachers) was not associated with adolescent smoking (OR=1.16, 95% CI: 0.88-1.53). School commitment was strongly associated with current smoking. It is important to further study this variable with the aim of ascertaining whether or not interventions that improve school commitment may prevent or reduce smoking amongst adolescent students.
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Pretest online discussion groups to augment teaching and learning.
Kuhn, Jonathan; Hasbargen, Barbara; Miziniak, Halina
2010-01-01
Tests and final examination scores of three semesters of control students in a nursing foundation course were compared with tests and final examination scores of three semesters of participating students. Participating students were offered access to an asynchronous pretest online discussion activity with a faculty e-moderator. While the simplified Bloom's revised taxonomy assisted in creating appropriate preparatory test and final examination questions for pretest online discussion, Salmon's five-stage online method provided direction to the e-moderator on how to encourage students to achieve Bloom's higher-order thinking skills during the pretest online discussions. Statistical analysis showed the pretest online discussion activity had a generally positive impact on tests and final examination scores, when controlling for a number of possible confounding variables, including instructor, cumulative grade point average, age, and credit hours.
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Bellera, Carine; Proust-Lima, Cécile; Joseph, Lawrence; Richaud, Pierre; Taylor, Jeremy; Sandler, Howard; Hanley, James; Mathoulin-Pélissier, Simone
2018-04-01
Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was not accounted for in the survival model. Conclusion Our modeling strategy was particularly flexible and accounted for multiple complex features of longitudinal and survival data, including the presence of a random changepoint and a time-dependent covariate.
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Causal Methods for Observational Research: A Primer.
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.
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Nelson, Jennifer Clark; Marsh, Tracey; Lumley, Thomas; Larson, Eric B; Jackson, Lisa A; Jackson, Michael L
2013-08-01
Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased owing to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias. We applied two such methods, namely imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method's ability to reduce bias using the control time period before influenza circulation. Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not use the validation sample confounders. Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from health care database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which the data can be imputed or reweighted using the additional validation sample information. Copyright © 2013 Elsevier Inc. All rights reserved.
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Nelson, Jennifer C.; Marsh, Tracey; Lumley, Thomas; Larson, Eric B.; Jackson, Lisa A.; Jackson, Michael
2014-01-01
Objective Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased due to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias. Study Design and Setting We applied two such methods, imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method’s ability to reduce bias using the control time period prior to influenza circulation. Results Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not utilize the validation sample confounders. Conclusion Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from healthcare database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which data can be imputed or reweighted using the additional validation sample information. PMID:23849144
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Antidepressant sales and regional variations of suicide mortality in Germany.
Blüml, Victor; Helbich, Marco; Mayr, Michael; Turnwald, Roland; Vyssoki, Benjamin; Lewitzka, Ute; Hartung, Sebastian; Plener, Paul L; Fegert, Jörg M; Kapusta, Nestor D
2017-04-01
Suicides account for over one million deaths per year worldwide with depression among the most important risk factors. Epidemiological research into the relationship between antidepressant utilization and suicide mortality has shown heterogeneous and contradictory results. Different methodological approaches and limitations could at least partially explain varying results. This is the first study assessing the association of suicide mortality and antidepressant sales across Germany using complex statistical approaches in order to control for possible confounding factors including spatial dependency of data. German suicide counts were analyzed on a district level (n = 402) utilizing ecological Poisson regressions within a hierarchical Bayesian framework. Due to significant spatial effects between adjacent districts spatial models were calculated in addition to a baseline non-spatial model. Models were adjusted for several confounders including socioeconomic variables, quality of psychosocial care, and depression prevalence. Separate analyses were performed for Eastern and Western Germany and for different classes of antidepressants (SSRIs and TCAs). Overall antidepressant sales were significantly negatively associated with suicide mortality in the non-spatial baseline model, while after adjusting for spatially structured and unstructured effects the association turned out to be insignificant. In sub-analyses, analogue results were found for SSRIs and TCAs separately. Suicide risk shows a distinct heterogeneous pattern with a pronounced relative risk in Southeast Germany. In conclusion, the results reflect the heterogeneous findings of previous studies on the association between suicide mortality and antidepressant sales and point to the complexity of this hypothesized link. Furthermore, the findings support tailored suicide preventive efforts within high risk areas. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Antipsychotic Response Worsens With Postmenopausal Duration in Women With Schizophrenia.
González-Rodríguez, Alexandre; Catalán, Rosa; Penadés, Rafael; Ruiz Cortés, Victoria; Torra, Mercè; Seeman, Mary V; Bernardo, Miquel
2016-12-01
The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia. Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response. Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms. Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.
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Yoon, Kyung Jae; Park, Jung Ho; Park, Jung Hwan; Jung, Il Seok
2014-01-01
Background/Aims The purpose of this study was to determine important manometric metrics for the analysis of pharyngeal and upper esophageal sphincter (UES) function and to investigate the effect of viscosity and other confounding factors on manometric results. Methods Manometric studies were performed on 26 asymptomatic volunteers (12 men and 14 women; age, 19–81 years). The manometric protocol included 5 water swallows (5 mL), 5 barium swallows (5 mL) and 5 yogurt swallows (5 mL). Evaluation of high-resolution manometry parameters including basal pressure of the UES, mesopharyngeal contractile integral (mesopharyngeal CI, mmHg · cm · sec), CI of the hypopharynx and UES (hypopharyngeal CI), relaxation interval of UES, median intrabolus pressure and nadir pressure at UES was performed using MATLAB. Results Mesopharyngeal CIs for barium and yogurt swallows were significantly lower than those for water swallows (both P < 0.05). Hypopharyngeal CIs for water swallows were significantly lower than those for barium swallows (P = 0.004), and median bolus pressure at UES for barium swallows was significantly higher than that for water and yogurt swallows (both P < 0.05). Furthermore, hypopharyngeal CI and median intrabolus pressure at UES were significantly related to age for 3 swallows (all P < 0.01 and P < 0.05, respectively). A significant negative correlation was also noted between nadir pressure at UES and age for water and yogurt swallows (all P < 0.05). Conclusions Manometric measurement of the pharynx and UES varies with respect to viscosity. Moreover, age could be a confounding variable in the interpretation of pharyngeal manometry. PMID:24847841
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Drosophila melanogaster as a model system for the evaluation of anti-aging compounds.
Jafari, Mahtab
2010-01-01
Understanding the causes of aging is a complex problem due to the multiple factors that influence aging, which include genetics, environment, metabolism and reproduction, among others. These multiple factors create logistical difficulties in the evaluation of anti-aging agents. There is a need for good model systems to evaluate potential anti-aging compounds. The model systems used should represent the complexities of aging in humans, so that the findings may be extrapolated to human studies, but they should also present an opportunity to minimize the variables so that the experimental results can be accurately interpreted. In addition to positively affecting lifespan, the impact of the compound on the physiologic confounders of aging, including fecundity and the health span--the period of life where an organism is generally healthy and free from serious or chronic illness--of the model organism needs to be evaluated. Fecundity is considered a major confounder of aging in fruit flies. It is well established that female flies that are exposed to toxic substances typically reduce their dietary intake and their reproductive output and display an artifactual lifespan extension. As a result, drugs that achieve longevity benefits by reducing fecundity as a result of diminished food intake are probably not useful candidates for eventual treatment of aging in humans and should be eliminated during the screening process. Drosophila melanogaster provides a suitable model system for the screening of anti-aging compounds as D. melanogaster and humans have many conserved physiological and biological pathways. In this paper, I propose an algorithm to screen anti-aging compounds using Drosophila melanogaster as a model system.
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Jiang, Jing; Zhao, You-Jin; Hu, Xin-Yu; Du, Ming-Ying; Chen, Zi-Qi; Wu, Min; Li, Kai-Ming; Zhu, Hong-Yan; Kumar, Poornima; Gong, Qi-Yong
2017-01-01
Background Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD. PMID:27780031
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Esteban-Cornejo, I; Tejero-González, C M; Castro-Piñero, J; Conde-Caveda, J; Cabanas-Sanchez, V; Sallis, J F; Veiga, Óscar L
2015-06-01
Unhealthy body composition is a cause for concern across the lifespan. The objective of this study was to examine the independent and combined associations between neonatal and current body composition with academic performance among youth. This cross-sectional study was conducted with a total of 1557 youth (745 girls) aged 10.4 ± 3.4 years. Birth weight and length at birth were self-reported. Current body composition was assessed by body mass index (BMI), waist circumference (WC) and percentage of body fat (BF%). Academic performance was assessed through schools records. Birth weight was related to all academic variables in boys, independent of potential confounders, including BMI; whereas WC, BMI and BF% were related to all academic performance indicators in both boys and girls, independent of potential confounders, including birth weight (all P < 0.05). In addition, the combined adverse effects of low birth weight and current overweight on academic performance were observed in both boys and girls for grade point average (GPA) indicator. Boys in the group with none adverse effect had significantly higher scores in GPA (score +0.535; 95% confidence interval, 0.082-0.989) than boys in the group of both adverse effects (P < 0.007); among girls, GPA score was higher in the group with none adverse effect than in the groups with one or two adverse effects (P for trend = 0.029). Neonatal and current body composition, both independently and combined, may influence academic performance in youth. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.
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Romo-Romo, Alonso; Aguilar-Salinas, Carlos A.; Brito-Córdova, Griselda X.; Gómez Díaz, Rita A.; Vilchis Valentín, David
2016-01-01
Background The effects of non-nutritive sweeteners (NNS) on glucose metabolism and appetite regulating hormones are not clear. There is an ongoing debate concerning NNS use and deleterious changes in metabolism. Objectives The aim of this review is to analyze the scientific available evidence regarding the effects of NNS on glucose metabolism and appetite regulating hormones. Data Sources and Study Eligibility Criteria We identified human observational studies evaluating the relation between NNS consumption and obesity, diabetes, and metabolic syndrome, in addition to clinical trials evaluating the effects of NNS in glucose metabolism and appetite regulating hormones. Results Fourteen observational studies evaluating the association between NNS consumption and the development of metabolic diseases and twenty-eight clinical trials studying the effects of NNS on metabolism were included. Finally, two meta-analyses evaluating the association between the consumption of NNS-containing beverages and the development of type 2 diabetes were identified. Conclusions Some observational studies suggest an association between NNS consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in observational studies. The effects of the NNS on glucose metabolism are not clear. The results of the identified clinical trials are contradictory and are not comparable because of the major existing differences between them. Studies evaluating specific NNS, with an adequate sample size, including a homogeneous study group, identifying significant comorbidities, with an appropriate control group, with an appropriate exposure time, and considering adjustment for confounder variables such as adiposity are needed. PMID:27537496
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Puopolo, Maria; Ladogana, Anna; Vetrugno, Vito; Pocchiari, Maurizio
2011-07-01
The occurrence of transfusion transmissions of variant Creutzfeldt-Jakob disease (CJD) cases has reawakened attention to the possible similar risk posed by other forms of CJD. CJD with a definite or probable diagnosis (sporadic CJD, n = 741; genetic CJD, n = 175) and no-CJD patients with definite alternative diagnosis (n = 482) with available blood transfusion history were included in the study. The risk of exposure to blood transfusion occurring more than 10 years before disease onset and for some possible confounding factors was evaluated by calculating crude odds ratios (ORs). Variables with significant ORs in univariate analyses were included in multivariate logistic regression analyses. In the univariate model, blood transfusion occurring more than 10 years before clinical onset is 4.1-fold more frequent in sporadic CJD than in other neurologic disorders. This significance is lost when the 10-year lag time was not considered. Multivariate analyses show that the risk of developing sporadic CJD after transfusion increases (OR, 5.05) after adjusting for possible confounding factors. Analysis conducted on patients with genetic CJD did not reveal any significant risk factor associated with transfusion. This is the first case-control study showing a significant risk of transfusion occurring more than 10 years before clinical onset in sporadic CJD patients. It remains questionable whether the significance of these data is biologically plausible or the consequence of biases in the design of the study, but they counterbalance previous epidemiologic negative reports that might have overestimated the assessment of blood safety in sporadic CJD. © 2010 American Association of Blood Banks.
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ERIC Educational Resources Information Center
Soh, Kay Cheng
2012-01-01
University ranking has become ritualistic in higher education. Ranking results are taken as bona fide by rank users. Ranking systems usually use large data sets from highly heterogeneous universities of varied backgrounds. This poses the problem of Simpson's Paradox and the lurking variables causing it. Using QS 2011-2012 Ranking data, the dual…
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ERIC Educational Resources Information Center
Van Lieshout, Ryan J.; Schmidt, Louis A.; Robinson, Monique; Niccols, Alison; Boyle, Michael H.
2013-01-01
Recent research suggests that fetal exposure to increased maternal body mass index (BMI) during pregnancy may be associated with psychopathology later in life. When this link first emerges, and if it is due to intrauterine exposures or confounding variables is not known. We therefore assessed associations between maternal pre-pregnancy BMI and:…
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Reduced streamflow lowers dry-season growth of rainbow trout in a small stream
Bret C. Harvey; Rodney J. Nakamoto; Jason L. White
2006-01-01
A wide variety of resource management activities can affect surface discharge in small streams. Often, the effects of variation in streamflow on fish survival and growth can be difficult to estimate because of possible confounding with the effects of other variables, such as water temperature and fish density. We measured the effect of streamflow on survival and growth...
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John R. Donnelly
1971-01-01
Softwood stem cuttings from three mature sugar maple trees were treated with several types and concentrations of growth regulators. Lack of statistical significance was due to extreme variability in tree response: low levels of auxin stimulated rooting in two study trees, while auxins inhibited rooting in the other tree. It is postulated that variations in rooting...
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ERIC Educational Resources Information Center
Licht, Carolyn; Chabot, David
2006-01-01
Bowen's theory (1978) of differentiation is the personality variable most critical to mature development and the attainment of psychological health. The study of psychological differentiation has been confounded by confusion regarding the constructs being studied and the measurement tools used to assess them. The purpose of this review is to…
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ERIC Educational Resources Information Center
Hevel, Michael S.; Martin, Georgianna L.; Pascarella, Ernest T.
2014-01-01
We use a longitudinal national dataset to explore the effects of fraternity and sorority membership on students' socially responsible leadership in the fourth year of college. Controlling for a variety of potentially confounding variables, we find no net effect. These findings run counter to an earlier study based on the same students that found…
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ERIC Educational Resources Information Center
Boniface, Russell; Protheroe, Nancy
Class-size reduction (CSR) has been a complex and contentious issue for the last quarter century. Although the small-class concept was adopted because it appealed to common sense, research over time has revealed a mix of confounding variables, instead of a definitive conclusion. Some CSR efforts, such as Tennessee's Project STAR and Wisconsin's…
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Kaptein, Maurits; van Emden, Robin; Iannuzzi, Davide
2017-01-01
Due to the ubiquitous presence of treatment heterogeneity, measurement error, and contextual confounders, numerous social phenomena are hard to study. Precise control of treatment variables and possible confounders is often key to the success of studies in the social sciences, yet often proves out of the realm of control of the experimenter. To amend this situation we propose a novel approach coined "lock-in feedback" which is based on a method that is routinely used in high-precision physics experiments to extract small signals out of a noisy environment. Here, we adapt the method to noisy social signals in multiple dimensions and evaluate it by studying an inherently noisy topic: the perception of (subjective) beauty. We show that the lock-in feedback approach allows one to select optimal treatment levels despite the presence of considerable noise. Furthermore, through the introduction of an external contextual shock we demonstrate that we can find relationships between noisy variables that were hitherto unknown. We therefore argue that lock-in methods may provide a valuable addition to the social scientist's experimental toolbox and we explicitly discuss a number of future applications.
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Belek, I
2000-02-01
The aim of this study is to determine the separate effects of social class, income, education and area of residence on psychological distress. The study also assesses whether the association between prevalence of high score on the 12-item General Health Questionnaire (GHQ 12) and social class is independent of other variables. Psychological distress was assessed by means of the GHQ 12. The study covered 1,092 adults aged 15 years or more living in two different quarters of Antalya. Social class status was defined by occupational position, with income, education and area of residence treated as confounders. Chi-square and logistic regression analyses were used to evaluate the data. Large inequalities in psychological distress by all variables were observed. Psychological distress was significantly associated with class status, after adjusting for income, education, area of residence and other potential confounders (age, sex and marital status). Class inequalities in psychological distress were observed between blue-collar workers/unqualified employees and bourgeoisie. These findings support the view that the recent widening of inequalities among social classes in Turkey pose a substantial threat to health.
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Santos, Daniela M; Lage, Laís V; Jabur, Eleonora K; Kaziyama, Helena H S; Iosifescu, Dan V; De Lucia, Mara Cristina S; Fráguas, Renério
2017-01-01
We developed this study to investigate the association of fibromyalgia with personality traits, controlling for depression and other potential confounders. We assessed personality traits using the Cloninger's Temperament and Character Inventory (TCI) in 78 female patients with fibromyalgia and in a control group of 78 subjects without fibromyalgia. The Mini-International Neuropsychiatric Interview was used to assess depression and anxiety diagnoses. To investigate the association between fibromyalgia and the Cloninger's Temperament and Character Inventory we performed unadjusted and adjusted analyses of covariance, using the TCI score as dependent variable and adjusting the model for depression, anxiety and for clinical and socio-demographic variables. We used a backward selection method to choose the final model. In the unadjusted analysis, fibromyalgia was associated with all personality traits, except persistency. After adjusting for depression and anxiety, patients with fibromyalgia presented decreased novelty seeking compared to controls; the differences in other personality traits were no longer significant. Novelty seeking was also correlated with the length of history of fibromyalgia and pain intensity. Decreased novelty seeking may be a personality trait associated with fibromyalgia. Depression and anxiety should be considered potential confounders in the evaluation of personality traits in this population.
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2017-01-01
Due to the ubiquitous presence of treatment heterogeneity, measurement error, and contextual confounders, numerous social phenomena are hard to study. Precise control of treatment variables and possible confounders is often key to the success of studies in the social sciences, yet often proves out of the realm of control of the experimenter. To amend this situation we propose a novel approach coined “lock-in feedback” which is based on a method that is routinely used in high-precision physics experiments to extract small signals out of a noisy environment. Here, we adapt the method to noisy social signals in multiple dimensions and evaluate it by studying an inherently noisy topic: the perception of (subjective) beauty. We show that the lock-in feedback approach allows one to select optimal treatment levels despite the presence of considerable noise. Furthermore, through the introduction of an external contextual shock we demonstrate that we can find relationships between noisy variables that were hitherto unknown. We therefore argue that lock-in methods may provide a valuable addition to the social scientist’s experimental toolbox and we explicitly discuss a number of future applications. PMID:28306728
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Lee, Sunmin; Zhai, Shumenghui; Zhang, Guo (Yolanda); Ma, Xiang S; Lu, Xiaoxiao; Tan, Yin; Siu, Philip; Seals, Brenda; Ma, Grace X
2015-01-01
BACKGROUND Hepatitis C virus (HCV) is a major cause of chronic liver disease and cancer. Vietnamese Americans are at high risk of HCV infection, with men having the highest US incidence of liver cancer. This study examines an intervention to improve HCV knowledge among Vietnamese Americans. STUDY Seven Vietnamese community-based organizations in Pennsylvania and New Jersey recruited a total of 306 Vietnamese participants from 2010 to 2011. RESULTS Average knowledge scores for pretest and posttest were 3.32 and 5.88, respectively (maximum 10). After adjusting for confounding variables, age and higher education were positively associated with higher pretest scores and having a physician who spoke English or Vietnamese was negatively associated with higher pretest scores. Additionally, after adjusting for confounding variables, household income, education, and having an HCV-infected family member significantly increased knowledge scores. CONCLUSIONS Promotion and development of HCV educational programs can increase HCV knowledge among race and ethnic groups, such as Vietnamese Americans. Giving timely information to at-risk groups provides the opportunity to correct misconceptions, decrease HCV risk behaviors, and encourage testing that might improve timely HCV diagnosis and treatment. PMID:26561280
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Genetic Instrumental Variable Studies of Effects of Prenatal Risk Factors
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
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Confounder summary scores when comparing the effects of multiple drug exposures.
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.
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Sources of Variance in Baseline Gene Expression in the Rodent Liver
Corton, J. Christopher; Bushel, Pierre R.; Fostel, Jennifer; O'Lone, Raegan B.
2012-01-01
The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variation due to individual, environmental, and technical factors. Analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in liver gene expression in the rodent. Here, studies which highlight contributions of different factors to gene expression variability in the rodent liver are discussed including a large meta-analysis of rat liver, which identified genes that vary in control animals in the absence of chemical treatment. Genes and their pathways that are the most and least variable were identified in a number of these studies. Life stage, fasting, sex, diet, circadian rhythm and liver lobe source can profoundly influence gene expression in the liver. Recognition of biological and technical factors that contribute to variability of background gene expression can help the investigator in the design of an experiment that maximizes sensitivity and reduces the influence of confounders that may lead to misinterpretation of genomic changes. The factors that contribute to variability in liver gene expression in rodents are likely analogous to those contributing to human interindividual variability in drug response and chemical toxicity. Identification of batteries of genes that are altered in a variety of background conditions could be used to predict responses to drugs and chemicals in appropriate models of the human liver. PMID:22230429
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Methodological concerns for meta-analyses of meditation: Comment on Sedlmeier et al. (2012).
Orme-Johnson, David W; Dillbeck, Michael C
2014-03-01
We commend Sedlmeier et al. (2012) for their significant undertaking of meta-analysis of all meditation types on all psychological variables, but additional analyses may modify some of their conclusions. Whereas they suggest from visual inspection of funnel diagrams that there may be publication bias of underreporting low-effect studies on the Transcendental Meditation (TM) technique, quantitative tests do not indicate the presence of bias for any type of meditation. We additionally found that there was no significant difference in effect sizes between studies originating from researchers affiliated with a TM organization and studies from other universities. We found that comparison of different types of meditation on their global index was confounded because their global index aggregated different sets of variables for the different groups. That is, using composite indices that only aggregated variables for which each group had at least 3 studies confirmed the authors' conclusion that effect sizes for different research designs were not different, but found that effect sizes for the TM technique were significantly larger than effect sizes for mindfulness meditation or other meditations. We also located 35 studies on the TM technique that appear to meet the authors' inclusion criteria that were missed by their meta-analysis, and several others on important psychosocial behavioral variables, such as job performance, substance abuse, and prison recidivism that were not reviewed. In addition, we suggest that future meta-analyses on psychological variables include cross-validating physiological studies.
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Do, D. Phuong; Wang, Lu; Elliott, Michael R.
2013-01-01
Extant observational studies generally support the existence of a link between neighborhood context and health. However, estimating the causal impact of neighborhood effects from observational data has proven to be a challenge. Omission of relevant factors may lead to overestimating the effects of neighborhoods on health while inclusion of time-varying confounders that may also be mediators (e.g., income, labor force status) may lead to underestimation. Using longitudinal data from the 1990 to 2007 years of the Panel Study of Income Dynamics, this study investigates the link between neighborhood poverty and overall mortality risk. A marginal structural modeling strategy is employed to appropriately adjust for simultaneous mediating and confounding factors. To address the issue of possible upward bias from the omission of key variables, sensitivity analysis to assess the robustness of results against unobserved confounding is conducted. We examine two continuous measures of neighborhood poverty – single-point and a running average. Both were specified as piece-wise linear splines with a knot at 20 percent. We found no evidence from the traditional naïve strategy that neighborhood context influences mortality risk. In contrast, for both the single-point and running average neighborhood poverty specifications, the marginal structural model estimates indicated a statistically significant increase in mortality risk with increasing neighborhood poverty above the 20 percent threshold. For example, below 20 percent neighborhood poverty, no association was found. However, after the 20 percent poverty threshold is reached, each 10 percentage point increase in running average neighborhood poverty was found to increase the odds for mortality by 89 percent [95% CI = 1.22, 2.91]. Sensitivity analysis indicated that estimates were moderately robust to omitted variable bias. PMID:23849239
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Shakiba, Maryam; Mansournia, Mohammad Ali; Salari, Arsalan; Soori, Hamid; Mansournia, Nasrin; Kaufman, Jay S
2018-06-01
In longitudinal studies, standard analysis may yield biased estimates of exposure effect in the presence of time-varying confounders that are also intermediate variables. We aimed to quantify the relationship between obesity and coronary heart disease (CHD) by appropriately adjusting for time-varying confounders. This study was performed in a subset of participants from the Atherosclerosis Risk in Communities (ARIC) Study (1987-2010), a US study designed to investigate risk factors for atherosclerosis. General obesity was defined as body mass index (weight (kg)/height (m)2) ≥30, and abdominal obesity (AOB) was defined according to either waist circumference (≥102 cm in men and ≥88 cm in women) or waist:hip ratio (≥0.9 in men and ≥0.85 in women). The association of obesity with CHD was estimated by G-estimation and compared with results from accelerated failure-time models using 3 specifications. The first model, which adjusted for baseline covariates, excluding metabolic mediators of obesity, showed increased risk of CHD for all obesity measures. Further adjustment for metabolic mediators in the second model and time-varying variables in the third model produced negligible changes in the hazard ratios. The hazard ratios estimated by G-estimation were 1.15 (95% confidence interval (CI): 0.83, 1.47) for general obesity, 1.65 (95% CI: 1.35, 1.92) for AOB based on waist circumference, and 1.38 (95% CI: 1.13, 1.99) for AOB based on waist:hip ratio, suggesting that AOB increased the risk of CHD. The G-estimated hazard ratios for both measures were further from the null than those derived from standard models.
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Harvey, Samuel B; Sellahewa, Dilan A; Wang, Min-Jung; Milligan-Saville, Josie; Bryan, Bridget T; Henderson, Max; Hatch, Stephani L; Mykletun, Arnstein
2018-06-01
Long-standing concerns exist about reverse causation and residual confounding in the prospective association between job strain and risk of future common mental disorders. We aimed to address these concerns through analysis of data collected in the UK National Child Development Study, a large British cohort study. Data from the National Child Development Study (n=6870) were analysed by use of multivariate logistic regression to investigate the prospective association between job strain variables at age 45 years and risk of future common mental disorders at age 50 years, controlling for lifetime psychiatric history and a range of other possible confounding variables across the lifecourse. Population attributable fractions were calculated to estimate the public health effect of job strain on midlife mental health. In the final model, adjusted for all measured confounders, high job demands (odds ratio 1·70, 95% CI 1·25-2·32; p=0·0008), low job control (1·89, 1·29-2·77; p=0·0010), and high job strain (2·22, 1·59-3·09; p<0·0001) remained significant independent predictors of future onset of common mental disorder. If causality is assumed, our findings suggest that 14% of new cases of common mental disorder could have been prevented through elimination of high job strain (population attributable fraction 0·14, 0·06-0·20). High job strain appears to independently affect the risk of future common mental disorders in midlife. These findings suggest that modifiable work-related risk factors might be an important target in efforts to reduce the prevalence of common mental disorders. iCare Foundation and Mental Health Branch, NSW Health. Copyright © 2018 Elsevier Ltd. All rights reserved.
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La Gamba, Fabiola; Corrao, Giovanni; Romio, Silvana; Sturkenboom, Miriam; Trifirò, Gianluca; Schink, Tania; de Ridder, Maria
2017-10-01
Clustering of patients in databases is usually ignored in one-stage meta-analysis of multi-database studies using matched case-control data. The aim of this study was to compare bias and efficiency of such a one-stage meta-analysis with a two-stage meta-analysis. First, we compared the approaches by generating matched case-control data under 5 simulated scenarios, built by varying: (1) the exposure-outcome association; (2) its variability among databases; (3) the confounding strength of one covariate on this association; (4) its variability; and (5) the (heterogeneous) confounding strength of two covariates. Second, we made the same comparison using empirical data from the ARITMO project, a multiple database study investigating the risk of ventricular arrhythmia following the use of medications with arrhythmogenic potential. In our study, we specifically investigated the effect of current use of promethazine. Bias increased for one-stage meta-analysis with increasing (1) between-database variance of exposure effect and (2) heterogeneous confounding generated by two covariates. The efficiency of one-stage meta-analysis was slightly lower than that of two-stage meta-analysis for the majority of investigated scenarios. Based on ARITMO data, there were no evident differences between one-stage (OR = 1.50, CI = [1.08; 2.08]) and two-stage (OR = 1.55, CI = [1.12; 2.16]) approaches. When the effect of interest is heterogeneous, a one-stage meta-analysis ignoring clustering gives biased estimates. Two-stage meta-analysis generates estimates at least as accurate and precise as one-stage meta-analysis. However, in a study using small databases and rare exposures and/or outcomes, a correct one-stage meta-analysis becomes essential. Copyright © 2017 John Wiley & Sons, Ltd.
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Knowlden, Adam P; Burns, Maranda; Harcrow, Andy; Shewmake, Meghan E
2016-03-16
Poor sleep quality is a significant public health problem. The role of nutrition in predicting sleep quality is a relatively unexplored area of inquiry. The purpose of this study was to evaluate the capacity of 10 food choice categories, sleep confounding beverages, and psychological distress to predict the sleep quality of college students. A logistic regression model comprising 10 food choice variables (healthy proteins, unhealthy proteins, healthy dairy, unhealthy dairy, healthy grains, unhealthy grains, healthy fruits and vegetables, unhealthy empty calories, healthy beverages, unhealthy beverages), sleep confounding beverages (caffeinated/alcoholic beverages), as well as psychological distress (low, moderate, serious distress) was computed to determine the capacity of the variables to predict sleep quality (good/poor). The odds of poor sleep quality were 32.4% lower for each unit of increased frequency of healthy proteins consumed (p<0.001; OR=0.676), 14.1% lower for each unit of increased frequency of healthy dairy food choices consumed (p=0.024; OR=0.859), 13.1% higher for each unit of increased frequency of empty calorie food choices consumed (p=0.003; OR=1.131), and 107.3% higher for those classified in the moderate psychological distress (p=0.016; OR=2.073). Collectively, healthy proteins, healthy dairy, unhealthy empty calories, and moderate psychological distress were moderately predictive of sleep quality in the sample (Nagelkerke R2=23.8%). Results of the study suggested higher frequency of consumption of healthy protein and healthy dairy food choices reduced the odds of poor sleep quality, while higher consumption of empty calories and moderate psychological distress increased the odds of poor sleep quality.
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Park, Soojin; Steiner, Peter M; Kaplan, David
2018-06-01
Considering that causal mechanisms unfold over time, it is important to investigate the mechanisms over time, taking into account the time-varying features of treatments and mediators. However, identification of the average causal mediation effect in the presence of time-varying treatments and mediators is often complicated by time-varying confounding. This article aims to provide a novel approach to uncovering causal mechanisms in time-varying treatments and mediators in the presence of time-varying confounding. We provide different strategies for identification and sensitivity analysis under homogeneous and heterogeneous effects. Homogeneous effects are those in which each individual experiences the same effect, and heterogeneous effects are those in which the effects vary over individuals. Most importantly, we provide an alternative definition of average causal mediation effects that evaluates a partial mediation effect; the effect that is mediated by paths other than through an intermediate confounding variable. We argue that this alternative definition allows us to better assess at least a part of the mediated effect and provides meaningful and unique interpretations. A case study using ECLS-K data that evaluates kindergarten retention policy is offered to illustrate our proposed approach.
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Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Pérez-Román, Diana I; Pérez-Dorame, Renzo; Mateos-Toledo, Heidegger; Mejía, Mayra
2017-07-01
Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02-0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003-1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.
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Effect of Placenta Previa on Preeclampsia
Ying, Hao; Lu, Yi; Dong, Yi-Nuo; Wang, De-Fen
2016-01-01
Background The correlation between gestational hypertension-preeclampsia (GH-PE) and placenta previa (PP) is controversial. Specifically, it is unknown whether placenta previa has any effect on the various types of preeclampsia (PE), and the role PP with concurrent placenta accreta (PA) play in the occurrence of GH-PE are not well understood. Objective The aim of this study was to identify the effects of PP on GH, mild and severe preeclampsia (MPE and SPE), and early- and late-onset preeclampsia (EPE and LPE). Another aim of the study was to determine if concurrent PA impacts the relationship between PP and GH-PE. Methods A retrospective single-center study of 1,058 patients having singleton pregnancies with PP was performed, and 2,116 pregnant women were randomly included as controls. These cases were collected from a tertiary hospital and met the inclusion criteria for the study. Clinical information, including PP and the gestational age at the onset of GH-PE were collected. Binary and multiple logistic regression analyses were conducted after the confounding variables were controlled to assess the effects of PP on different types of GH-PE. Results There were 155 patients with GH-PE in the two groups. The incidences of GH-PE in the PP group and the control group were 2.5% (26/1058) and 6.1% (129/2116), respectively (P = 0.000). Binary and multiple regression analyses were conducted after controlling for confounding variables. Compared to the control group, in the PP group, the risk of GH-PE was reduced significantly by 78% (AOR: 0.216; 95% CI: 0.135–0.345); the risks of GH and PE were reduced by 55% (AOR: 0.451; 95% CI: 0.233–0.873) and 86% (AOR: 0.141; 95% CI: 0.073–0.271), respectively; the risks of MPE and SPE were reduced by 73% (AOR: 0.269; 95% CI: 0.087–0828) and 88% (AOR: 0.123; 95% CI: 0.055–0.279), respectively; and the risks of EPE and LPE were reduced by 95% (AOR: 0.047; 95% CI: 0.012–0.190) and 67% (AOR: 0.330; 95% CI: 0.153–0.715), respectively. The incidence of concurrent PA in women with PP was 5.86%; PP with PA did not significantly further reduce the incidence of GH-PE compared with PP without PA (1.64% vs. 2.51%, P>0.05). Binary logistic regression analyses were conducted after controlling for confounding variables, compared with the non-PP + GH-PE group, and the AOR of FGR in the non-PP + non-GH-PE group was 0.206 (0.124–0.342). Compared with the PP + GH-PE group, the AOR of FGR in the PP + non-GH-PE group was 0.430 (0.123–1.500). Conclusion PP is not only associated with a significant reduction in the incidence of GH-PE, but also is associated with a reduction in incidence of various types of PE. Concurrent PA and PP do not show association with a reduction in incidence of GH-PE. PMID:26731265
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Wendel, Jochen; Buttenfield, Barbara P.; Stanislawski, Larry V.
2016-01-01
Knowledge of landscape type can inform cartographic generalization of hydrographic features, because landscape characteristics provide an important geographic context that affects variation in channel geometry, flow pattern, and network configuration. Landscape types are characterized by expansive spatial gradients, lacking abrupt changes between adjacent classes; and as having a limited number of outliers that might confound classification. The US Geological Survey (USGS) is exploring methods to automate generalization of features in the National Hydrography Data set (NHD), to associate specific sequences of processing operations and parameters with specific landscape characteristics, thus obviating manual selection of a unique processing strategy for every NHD watershed unit. A chronology of methods to delineate physiographic regions for the United States is described, including a recent maximum likelihood classification based on seven input variables. This research compares unsupervised and supervised algorithms applied to these seven input variables, to evaluate and possibly refine the recent classification. Evaluation metrics for unsupervised methods include the Davies–Bouldin index, the Silhouette index, and the Dunn index as well as quantization and topographic error metrics. Cross validation and misclassification rate analysis are used to evaluate supervised classification methods. The paper reports the comparative analysis and its impact on the selection of landscape regions. The compared solutions show problems in areas of high landscape diversity. There is some indication that additional input variables, additional classes, or more sophisticated methods can refine the existing classification.
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Poverty, Pregnancy, and Birth Outcomes: A Study of the Earned Income Tax Credit.
Hamad, Rita; Rehkopf, David H
2015-09-01
Economic interventions are increasingly recognised as a mechanism to address perinatal health outcomes among disadvantaged groups. In the US, the earned income tax credit (EITC) is the largest poverty alleviation programme. Little is known about its effects on perinatal health among recipients and their children. We exploit quasi-random variation in the size of EITC payments to examine the effects of income on perinatal health. The study sample includes women surveyed in the 1979 National Longitudinal Survey of Youth (n = 2985) and their children born during 1986-2000 (n = 4683). Outcome variables include utilisation of prenatal and postnatal care, use of alcohol and tobacco during pregnancy, term birth, birthweight, and breast-feeding status. We first examine the health effects of both household income and EITC payment size using multivariable linear regressions. We then employ instrumental variables analysis to estimate the causal effect of income on perinatal health, using EITC payment size as an instrument for household income. We find that EITC payment size is associated with better levels of several indicators of perinatal health. Instrumental variables analysis, however, does not reveal a causal association between household income and these health measures. Our findings suggest that associations between income and perinatal health may be confounded by unobserved characteristics, but that EITC income improves perinatal health. Future studies should continue to explore the impacts of economic interventions on perinatal health outcomes, and investigate how different forms of income transfers may have different impacts. © 2015 John Wiley & Sons Ltd.
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Pousa, Esther; Duñó, Rosó; Blas Navarro, J; Ruiz, Ada I; Obiols, Jordi E; David, Anthony S
2008-05-01
Poor insight and impairment in Theory of Mind (ToM) reasoning are common in schizophrenia, predicting poorer clinical and functional outcomes. The present study aimed to explore the relationship between these phenomena. 61 individuals with a DSM-IV diagnosis of schizophrenia during a stable phase were included. ToM was assessed using a picture sequencing task developed by Langdon and Coltheart (1999), and insight with the Scale to Assess Unawareness of Mental Disorder (SUMD; Amador et al., 1993). Multivariate linear regression analysis was carried out to estimate the predictive value of insight on ToM, taking into account several possible confounders and interaction variables. No direct significant associations were found between any of the insight dimensions and ToM using bivariate analysis. However, a significant linear regression model which explained 48% of the variance in ToM was revealed in the multivariate analysis. This included the 5 insight dimensions and 3 interaction variables. Misattribution of symptoms--in aware patients with age at onset >20 years--and unawareness of need for medication--in patients with GAF >60--were significantly predictive of better ToM. Insight and ToM are two complex and distinct phenomena in schizophrenia. Relationships between them are mediated by psychosocial, clinical, and neurocognitive variables. Intact ToM may be a prerequisite for aware patients to attribute their symptoms to causes other than mental illness, which could in turn be associated with denial of need for medication.
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Developments in Post-marketing Comparative Effectiveness Research
S, Schneeweiss
2010-01-01
Physicians and insurers need to weigh the effectiveness of new drugs against existing therapeutics in routine care to make decisions about treatment and formularies. Because Food and Drug Administration (FDA) approval of most new drugs requires demonstrating efficacy and safety against placebo, there is limited interest by manufacturers in conducting such head-to-head trials. Comparative effectiveness research seeks to provide head-to-head comparisons of treatment outcomes in routine care. Health-care utilization databases record drug use and selected health outcomes for large populations in a timely way and reflect routine care, and therefore may be the preferred data source for comparative effectiveness research. Confounding caused by selective prescribing based on indication, severity, and prognosis threatens the validity of non-randomized database studies that often have limited details on clinical information. Several recent developments may bring the field closer to acceptable validity, including approaches that exploit the concepts of proxy variables using high-dimensional propensity scores, within-patient variation of drug exposure using crossover designs, and between-provider variation in prescribing preference using instrumental variable (IV) analyses. PMID:17554243
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[Referral to internal medicine for alcoholism: influence on follow-up care].
Avila, P; Marcos, M; Avila, J J; Laso, F J
2008-11-01
The problem of high rates of patient drop-out in alcohol treatment programs is frequently reported in the literature. Our aim was to investigate if internal medicine referral could improve abstinence and retention rates in a cohort of alcoholic patients. A retrospective observational study was conducted comparing 200 alcoholic patients attending a psychiatric unit (group 1) with 100 patients attending both this unit and an internal medicine unit (group 2). We collected sociodemographic and clinical variables and analysed differences regarding abstinence and retention rates by means of univariate and multivariate analysis. At 3 and 12 months follow-up, group 2 patients had higher retention and abstinence rates than group 1 patients. Multivariate analysis including potential confounding variables showed that independent predictors of one-year retention were internal medicine referral and being married. Independent predictors of one-year abstinence were being married, age > 44 years and receipt of drug treatment. The higher retention rate found among patients referred to Internal Medicine specialists, a result that has not been previously reported to the best of our knowledge, emphasizes the importance of a multidisciplinary team approach in the treatment of alcoholism.
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Collins, Linda M.; Dziak, John J.; Li, Runze
2009-01-01
An investigator who plans to conduct experiments with multiple independent variables must decide whether to use a complete or reduced factorial design. This article advocates a resource management perspective on making this decision, in which the investigator seeks a strategic balance between service to scientific objectives and economy. Considerations in making design decisions include whether research questions are framed as main effects or simple effects; whether and which effects are aliased (confounded) in a particular design; the number of experimental conditions that must be implemented in a particular design and the number of experimental subjects the design requires to maintain the desired level of statistical power; and the costs associated with implementing experimental conditions and obtaining experimental subjects. In this article four design options are compared: complete factorial, individual experiments, single factor, and fractional factorial designs. Complete and fractional factorial designs and single factor designs are generally more economical than conducting individual experiments on each factor. Although relatively unfamiliar to behavioral scientists, fractional factorial designs merit serious consideration because of their economy and versatility. PMID:19719358
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Challenges in Measuring Outcomes Following Digital Replantation
Sebastin, Sandeep J.; Chung, Kevin C.
2013-01-01
In the early period of replantation surgery, the emphasis was on digit survival. Subsequently, with better microsurgical techniques and instrumentation, the focus has shifted to function and in recent years to consideration of cost-effectiveness. Despite over 40 years of effort in refining digital replantation surgery, a rigorous evaluation of the outcomes of digital replantation has not been performed. This is because of the many confounding variables that influence outcome comparisons. These variables include the mechanism of injury (guillotine, crush, avulsion), the injury itself (total, near total, subtotal, partial amputation), and the surgical procedure (replantation, revascularization). In addition, the traditional outcome measures (two-point discrimination, range of motion, grip strength, or the ability to return to work) are reported inconsistently and vary widely among publications. All these factors make meaningful comparison of outcomes difficult. The recent emphasis on outcome research and cost-effectiveness necessitates a rethinking in the way we report outcomes of digital replantation. In this article, the authors summarize the challenges in assessing outcomes of digital replantation and explain the need to measure outcomes using rigorous clinical research designs that incorporate cost-effectiveness studies in the research protocol. PMID:24872766
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Goldstein, Risë B.; Smith, Sharon M.; Dawson, Deborah A.; Grant, Bridget F.
2016-01-01
Incidence rates of alcohol and drug use disorders (AUDs and DUDs) are consistently higher in men than women, but information on whether sociodemographic and psychiatric diagnostic predictors of AUD and DUD incidence differ by sex is limited. Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, sex-specific 3-year incidence rates of AUDs and DUDs among United States adults were compared by sociodemographic variables and baseline psychiatric disorders. Sex-specific logistic regression models estimated odds ratios for prediction of incident AUDs and DUDs, adjusting for potentially confounding baseline sociodemographic and diagnostic variables. Few statistically significant sex differences in predictive relationships were identified and those observed were generally modest. Prospective research is needed to identify predictors of incident DSM-5 AUDs and DUDs and their underlying mechanisms, including whether there is sex specificity by developmental phase, in the role of additional comorbidity in etiology and course, and in outcomes of prevention and treatment. PMID:26727008
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Integrated presentation of ecological risk from multiple stressors
NASA Astrophysics Data System (ADS)
Goussen, Benoit; Price, Oliver R.; Rendal, Cecilie; Ashauer, Roman
2016-10-01
Current environmental risk assessments (ERA) do not account explicitly for ecological factors (e.g. species composition, temperature or food availability) and multiple stressors. Assessing mixtures of chemical and ecological stressors is needed as well as accounting for variability in environmental conditions and uncertainty of data and models. Here we propose a novel probabilistic ERA framework to overcome these limitations, which focusses on visualising assessment outcomes by construct-ing and interpreting prevalence plots as a quantitative prediction of risk. Key components include environmental scenarios that integrate exposure and ecology, and ecological modelling of relevant endpoints to assess the effect of a combination of stressors. Our illustrative results demonstrate the importance of regional differences in environmental conditions and the confounding interactions of stressors. Using this framework and prevalence plots provides a risk-based approach that combines risk assessment and risk management in a meaningful way and presents a truly mechanistic alternative to the threshold approach. Even whilst research continues to improve the underlying models and data, regulators and decision makers can already use the framework and prevalence plots. The integration of multiple stressors, environmental conditions and variability makes ERA more relevant and realistic.
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Integrated presentation of ecological risk from multiple stressors.
Goussen, Benoit; Price, Oliver R; Rendal, Cecilie; Ashauer, Roman
2016-10-26
Current environmental risk assessments (ERA) do not account explicitly for ecological factors (e.g. species composition, temperature or food availability) and multiple stressors. Assessing mixtures of chemical and ecological stressors is needed as well as accounting for variability in environmental conditions and uncertainty of data and models. Here we propose a novel probabilistic ERA framework to overcome these limitations, which focusses on visualising assessment outcomes by construct-ing and interpreting prevalence plots as a quantitative prediction of risk. Key components include environmental scenarios that integrate exposure and ecology, and ecological modelling of relevant endpoints to assess the effect of a combination of stressors. Our illustrative results demonstrate the importance of regional differences in environmental conditions and the confounding interactions of stressors. Using this framework and prevalence plots provides a risk-based approach that combines risk assessment and risk management in a meaningful way and presents a truly mechanistic alternative to the threshold approach. Even whilst research continues to improve the underlying models and data, regulators and decision makers can already use the framework and prevalence plots. The integration of multiple stressors, environmental conditions and variability makes ERA more relevant and realistic.
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Developments in post-marketing comparative effectiveness research.
Schneeweiss, S
2007-08-01
Physicians and insurers need to weigh the effectiveness of new drugs against existing therapeutics in routine care to make decisions about treatment and formularies. Because Food and Drug Administration (FDA) approval of most new drugs requires demonstrating efficacy and safety against placebo, there is limited interest by manufacturers in conducting such head-to-head trials. Comparative effectiveness research seeks to provide head-to-head comparisons of treatment outcomes in routine care. Health-care utilization databases record drug use and selected health outcomes for large populations in a timely way and reflect routine care, and therefore may be the preferred data source for comparative effectiveness research. Confounding caused by selective prescribing based on indication, severity, and prognosis threatens the validity of non-randomized database studies that often have limited details on clinical information. Several recent developments may bring the field closer to acceptable validity, including approaches that exploit the concepts of proxy variables using high-dimensional propensity scores, within-patient variation of drug exposure using crossover designs, and between-provider variation in prescribing preference using instrumental variable (IV) analyses.
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Demographic factors, fatigue, and driving accidents: An examination of the published literature.
Di Milia, Lee; Smolensky, Michael H; Costa, Giovanni; Howarth, Heidi D; Ohayon, Maurice M; Philip, Pierre
2011-03-01
This article reviews the literature pertaining to the association between demographic variables (e.g., age, sex, race, socio-economic status) with fatigue, and when feasible, accident risk. It also explores their potential influence and interaction with some working arrangements, commute time, personality characteristics, and circadian chronotype. Fatigue has been implicated in a range of impairments that can have detrimental effects on individuals, and it is differentially associated with conventional demographic variables. However, several major methodological limitations prevent clear conclusions. First, there is absence of a shared definition both within and across disciplines. Second, although fatigue has been investigated using a variety of diverse designs, they have either been too weak to substantiate causality or lacked ecological validity. Third, while both subjective and objective measures have been used as dependent variables, fatigue has been more often found to be more strongly linked with the former. Fourth, with the exception of age and sex, the influence of other demographic variables is unknown, since they have not yet been concomitantly assessed. In instances when they have been assessed and included in statistical analyses, they are considered as covariates or confounders; thus, their contribution to the outcome variable is controlled for, rather than being a planned aspect of investigation. Because the interaction of demographic factors with fatigue is largely a neglected area of study, we recommend greater interdisciplinary collaborations, incorporation of multiple demographic variables as independent factors, and use of within-participant analyses. These recommendations would provide meaningful results that may be used to inform public policy and preventive strategies. Copyright © 2009 Elsevier Ltd. All rights reserved.
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A Behavior Genetic Investigation of Adolescent Motherhood and Offspring Mental Health Problems
Harden, K. Paige; Lynch, Stacy K.; Turkheimer, Eric; Emery, Robert E.; D’Onofrio, Brian M.; Slutske, Wendy S.; Waldron, Mary D.; Heath, Andrew C.; Statham, Dixie J.; Martin, Nicholas G.
2010-01-01
The present study examines the relations between adolescent motherhood and children’s behavior, substance use, and internalizing problems in a sample of 1,368 children of 712 female twins from Australia. Adolescent motherhood remained significantly associated with all mental health problems, even when using a quasiexperimental design capable of controlling for genetic and environmental confounds. However, the relation between adolescent motherhood and offspring behavior problems and substance use was partially confounded by family background variables that influence both generations. The results are consistent with a causal relation between adolescent motherhood and offspring mental health problems, and they highlight the usefulness of behavior genetic designs when examining putative environmental risks for the development of psychopathology. The generalizability of these results to the United States, which has a higher adolescent birth rate, is discussed. PMID:18020715
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The association between acculturation and hypertension in a multiethnic sample of US adults.
Teppala, Srinivas; Shankar, Anoop; Ducatman, Alan
2010-01-01
Previous studies analyzing acculturation and cardiovascular risk were restricted to individual race/ethnic groups and did not fully account for potential confounders. We examined the independent association between acculturation and hypertension in a contemporary multiethnic sample that included white, black, Latino, and Asian individuals. We examined 51,048 participants in the 2007 California Health Interview Survey who were >18 years, 59.5% of whom were women. The main exposure-of-interest was acculturation score, a summary measure of the additive effect of 4 variables (country of birth, parents' country of birth, language at home, and duration of stay in the United States) ranged from 0 (least acculturation) to 4 (highest acculturation). We found that increased acculturation was associated with hypertension, independent of age, gender, race/ethnicity, education, smoking, alcohol, physical activity, body mass index, and diabetes. Compared with those with the lowest acculturation (score of 0), the multivariable odds ratio (95% confidence interval) of hypertension among those with the highest acculturation (score of 4) was 1.78 (1.50-2.11). This association between acculturation and hypertension was consistent in subgroup analyses by gender, education, smoking, alcohol intake, and body mass index. Increased Western acculturation was found to be positively associated with hypertension in a multiethnic sample, independent of confounders. Copyright © 2010 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
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[Coffee consumption and type 2 diabetes mellitus].
Radzeviciene, Lina; Ostrauskas, Rytas
2009-01-01
The aim of the study was to determine the association between coffee consumption and the risk of type 2 diabetes mellitus. A case-control study included 234 cases with newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls who were free of the disease in 2001. Cases and controls were matched by gender and age (+/-5 years). Data on age, education level, occupation status, marital status, family history of diabetes, lifestyle (dietary habits, smoking habits, coffee consumption, alcohol consumption, physical activity), and stress were collected via a questionnaire. Variables were retained in models as confounders when their inclusion changed the value of the OR by more than 10% in any exposure category. Conditional logistic regression to compute the odds ratio (OR), 95% confidence interval (CI), and P for trend was used. After adjustment for possible confounders (family history of diabetes, body mass index, eating speed, morning exercise, cigarette smoking, years of education, and stress), a statistically significant relationship was observed between type 2 diabetes mellitus and coffee consumption. Individuals consuming four or more cups of coffee per day were at lower risk of 2 diabetes mellitus (OR=0.51; 95% CI, 0.27-0.97) compared to those who consumed one or less than one cup of coffee per day. Habitual coffee consumption of four or more cups per day might be related to the lower risk of type 2 diabetes mellitus.
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Differential expression analysis for RNAseq using Poisson mixed models.
Sun, Shiquan; Hood, Michelle; Scott, Laura; Peng, Qinke; Mukherjee, Sayan; Tung, Jenny; Zhou, Xiang
2017-06-20
Identifying differentially expressed (DE) genes from RNA sequencing (RNAseq) studies is among the most common analyses in genomics. However, RNAseq DE analysis presents several statistical and computational challenges, including over-dispersed read counts and, in some settings, sample non-independence. Previous count-based methods rely on simple hierarchical Poisson models (e.g. negative binomial) to model independent over-dispersion, but do not account for sample non-independence due to relatedness, population structure and/or hidden confounders. Here, we present a Poisson mixed model with two random effects terms that account for both independent over-dispersion and sample non-independence. We also develop a scalable sampling-based inference algorithm using a latent variable representation of the Poisson distribution. With simulations, we show that our method properly controls for type I error and is generally more powerful than other widely used approaches, except in small samples (n <15) with other unfavorable properties (e.g. small effect sizes). We also apply our method to three real datasets that contain related individuals, population stratification or hidden confounders. Our results show that our method increases power in all three data compared to other approaches, though the power gain is smallest in the smallest sample (n = 6). Our method is implemented in MACAU, freely available at www.xzlab.org/software.html. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Language outcomes at 12 years for children exposed prenatally to cocaine.
Lewis, Barbara A; Minnes, Sonia; Short, Elizabeth J; Min, Meeyoung O; Wu, Miaoping; Lang, Adelaide; Weishampel, Paul; Singer, Lynn T
2013-10-01
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. Children who were exposed to cocaine in utero (PCE; n = 183) and children who were not exposed to cocaine (i.e., no cocaine exposure [NCE]; n = 181) were followed prospectively from birth to 12 years of age and were compared on language subtests of the Test of Language Development-Intermediate, Third Edition ( Hammill & Newcomer, 1997b), and phonological processing as measured by the Comprehensive Test of Phonological Processing ( Wagner & Torgesen, 1999). The authors evaluated the relationship of PCE to language development through a multivariate analysis of covariance and regression analyses while controlling for confounders. Results show that PCE has small effects on specific aspects of language, including syntax and phonological processing. The caregiver variables of lower maternal vocabulary, more psychological symptoms, and a poorer home environment also had consistent effects on language and phonological processing scores. These findings suggest that PCE continues to have small, subtle effects on specific aspects of language at age 12 years. Phonological processing skills were significantly related to the reading outcomes of letter-word identification, reading fluency, and reading comprehension, indicating that PCE also has small but lasting effects on the language skills that are related to later literacy skills.
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Labor patterns in twin gestations
Leftwich, Heidi K.; Zaki, Mary N.; Wilkins, Isabelle; Hibbard, Judith U.
2014-01-01
Objective To compare labor progression in twin vs singleton gestations. Study Design Retrospective review of electronic database created by Consortium on Safe Labor, reflecting labor and delivery information from 12 clinical centers 2002-2008. Women with twin gestations, cephalic presentation of presenting twin, gestational age ≥34 weeks, with ≥2 cervical examinations were included. Exclusion criteria were fetal anomalies or demise. Singleton controls were selected by the same criteria. Categorical variables were analyzed by χ2; continuous by Student t test. Interval censored regression was used to determine distribution for time of cervical dilation in centimeters, or “traverse times,” and controlled for confounding factors. Repeated-measures analysis constructed mean labor curves by parity and number of fetuses. Results A total of 891 twin gestations were compared with 100,513 singleton controls. Twin gestations were more often older, white or African American, earlier gestational age, increased prepregnancy body mass index, and with lower birthweight. There was no difference in number of prior cesarean deliveries, induction, or augmentation, or epidural use. Median traverse times increased at every centimeter interval in nulliparous twins, in both unadjusted and adjusted analysis (P < .01). A similar pattern was noted for multiparas in both analyses. Labor curves demonstrated a delayed inflection point in the labor pattern for nulliparous and multiparous twin gestations. Conclusion Both nulliparous and multiparous women have slower progression of active phase labor with twins even when controlling for confounding factors. PMID:23871795
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Olivares, Pedro R; García-Rubio, Javier
2016-01-01
To analyze the associations between different components of fitness and fatness with academic performance, adjusting the analysis by sex, age, socio-economic status, region and school type in a Chilean sample. Data of fitness, fatness and academic performance was obtained from the Chilean System for the Assessment of Educational Quality test for eighth grade in 2011 and includes a sample of 18,746 subjects (49% females). Partial correlations adjusted by confounders were done to explore association between fitness and fatness components, and between the academic scores. Three unadjusted and adjusted linear regression models were done in order to analyze the associations of variables. Fatness has a negative association with academic performance when Body Mass Index (BMI) and Waist to Height Ratio (WHR) are assessed independently. When BMI and WHR are assessed jointly and adjusted by cofounders, WHR is more associated with academic performance than BMI, and only the association of WHR is positive. For fitness components, strength was the variable most associated with the academic performance. Cardiorespiratory capacity was not associated with academic performance if fatness and other fitness components are included in the model. Fitness and fatness are associated with academic performance. WHR and strength are more related with academic performance than BMI and cardiorespiratory capacity.
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2016-01-01
Objectives To analyze the associations between different components of fitness and fatness with academic performance, adjusting the analysis by sex, age, socio-economic status, region and school type in a Chilean sample. Methods Data of fitness, fatness and academic performance was obtained from the Chilean System for the Assessment of Educational Quality test for eighth grade in 2011 and includes a sample of 18,746 subjects (49% females). Partial correlations adjusted by confounders were done to explore association between fitness and fatness components, and between the academic scores. Three unadjusted and adjusted linear regression models were done in order to analyze the associations of variables. Results Fatness has a negative association with academic performance when Body Mass Index (BMI) and Waist to Height Ratio (WHR) are assessed independently. When BMI and WHR are assessed jointly and adjusted by cofounders, WHR is more associated with academic performance than BMI, and only the association of WHR is positive. For fitness components, strength was the variable most associated with the academic performance. Cardiorespiratory capacity was not associated with academic performance if fatness and other fitness components are included in the model. Conclusions Fitness and fatness are associated with academic performance. WHR and strength are more related with academic performance than BMI and cardiorespiratory capacity. PMID:27761345
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Access to Primary Care in US Counties Is Associated with Lower Obesity Rates.
Gaglioti, Anne H; Petterson, Stephen; Bazemore, Andrew; Phillips, Robert
2016-01-01
Obesity causes substantial morbidity and mortality in the United States. Evidence shows that primary care physician (PCP) supply correlates positively with improved health, but its association with obesity in the United States as not been adequately characterized. Our purpose was to characterize the association between PCP supply in US counties and adult obesity. We performed a multivariate logistic regression analysis to examine the relationship between county-level PCP supply and individual obesity status. We controlled for individual variables, including sex, race, marital status, income, and insurance status, and county-level variables, including rurality and poverty. Higher county-level PCP supply was associated with lower adult obesity after controlling for common confounders. Individuals living in counties with the most robust PCP supply were about 20% less likely to be obese (P ≤ .01) than those living in counties with the lowest PCP supply. While the observed association between the supply of PCPs and lower rates of obesity may not be causal, the association warrants further investigation. This may have important implications for restructuring the physician workforce in the context of the current PCP shortage and implementation of the Affordable Care Act and the patient-centered medical home. © Copyright 2016 by the American Board of Family Medicine.
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Stenset, V; Hofoss, D; Johnsen, L; Skinningsrud, A; Berstad, A E; Negaard, A; Reinvang, I; Gjerstad, L; Fladby, T
2008-12-01
To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values. 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42. WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.
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Lyvers, Michael; Mathieson, Nicole; Edwards, Mark S
2015-02-01
Acute alcohol intoxication has been found to increase perseverative errors on the Wisconsin Card Sorting Test, a well known neuropsychological index of prefrontal cortical functioning, in both laboratory and naturalistic settings. The present study examined the relationship between levels of alcohol consumption at campus drinking venues and performance of the Iowa Gambling Task (IGT), another neuropsychological test designed to assess prefrontal cortex dysfunction, after controlling for potential confounding variables including habitual alcohol intake (as a proxy for alcohol tolerance), trait impulsivity, and everyday executive functioning. The 49 participants of both genders aged 18 to 30years were recruited at the relevant venues and showed a broad range of blood alcohol concentrations (BACs) from virtually zero (.002%) to .19%. After controlling for demographic variables, habitual use of alcohol and illicit drugs, and frontal lobe related behavioural traits including impulsivity and disinhibition, BAC negatively predicted gambling money won on the last two trial blocks of the IGT. Trait impulsivity and habitual alcohol use were also significant predictors. Results are discussed in terms of acute effects of alcohol on brain systems and the behavioural consequences of such effects on decision making. Copyright © 2014 Elsevier Ltd. All rights reserved.
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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.
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Model building strategy for logistic regression: purposeful selection.
Zhang, Zhongheng
2016-03-01
Logistic regression is one of the most commonly used models to account for confounders in medical literature. The article introduces how to perform purposeful selection model building strategy with R. I stress on the use of likelihood ratio test to see whether deleting a variable will have significant impact on model fit. A deleted variable should also be checked for whether it is an important adjustment of remaining covariates. Interaction should be checked to disentangle complex relationship between covariates and their synergistic effect on response variable. Model should be checked for the goodness-of-fit (GOF). In other words, how the fitted model reflects the real data. Hosmer-Lemeshow GOF test is the most widely used for logistic regression model.
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Exploring heterogeneity in clinical trials with latent class analysis
Abarda, Abdallah; Contractor, Ateka A.; Wang, Juan; Dayton, C. Mitchell
2018-01-01
Case-mix is common in clinical trials and treatment effect can vary across different subgroups. Conventionally, a subgroup analysis is performed by dividing the overall study population by one or two grouping variables. It is usually impossible to explore complex high-order intersections among confounding variables. Latent class analysis (LCA) provides a framework to identify latent classes by observed manifest variables. Distal clinical outcomes and treatment effect can be different across these classes. This paper provides a step-by-step tutorial on how to perform LCA with R. A simulated dataset is generated to illustrate the process. In the example, the classify-analyze approach is employed to explore the differential treatment effects on distal outcomes across latent classes. PMID:29955579
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Hardin, Andrew
2017-09-01
In this issue, Bollen and Diamantopoulos (2017) defend causal-formative indicators against several common criticisms leveled by scholars who oppose their use. In doing so, the authors make several convincing assertions: Constructs exist independently from their measures; theory determines whether indicators cause or measure latent variables; and reflective and causal-formative indicators are both subject to interpretational confounding. However, despite being a well-reasoned, comprehensive defense of causal-formative indicators, no single article can address all of the issues associated with this debate. Thus, Bollen and Diamantopoulos leave a few fundamental issues unresolved. For example, how can researchers establish the reliability of indicators that may include measurement error? Moreover, how should researchers interpret disturbance terms that capture sources of influence related to both the empirical definition of the latent variable and to the theoretical definition of the construct? Relatedly, how should researchers reconcile the requirement for a census of causal-formative indicators with the knowledge that indicators are likely missing from the empirically estimated latent variable? This commentary develops 6 related research questions to draw attention to these fundamental issues, and to call for future research that can lead to the development of theory to guide the use of causal-formative indicators. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Factors Affecting the Clinical Success Rate of Miniscrew Implants for Orthodontic Treatment.
Jing, Zheng; Wu, Yeke; Jiang, Wenlu; Zhao, Lixing; Jing, Dian; Zhang, Nian; Cao, Xiaoqing; Xu, Zhenrui; Zhao, Zhihe
2016-01-01
The purpose of this study was to evaluate the various factors that influence the success rate of miniscrew implants used as orthodontic anchorage. Potential confounding variables examined were sex, age, vertical (FMA) and sagittal (ANB) skeletal facial pattern, site of placement (labial and buccal, palatal, and retromandibular triangle), arch of placement (maxilla and mandible), placement soft tissue type, oral hygiene, diameter and length of miniscrew implants, insertion method (predrilled or drill-free), angle of placement, onset and strength of force application, and clinical purpose. The correlations between success rate and overall variables were investigated by logistic regression analysis, and the effect of each variable on the success rate was utilized by variance analysis. One hundred fourteen patients were included with a total of 253 miniscrew implants. The overall success rate was 88.54% with an average loading period of 9.5 months in successful cases. Age, oral hygiene, vertical skeletal facial pattern (FMA), and general placement sites (maxillary and mandibular) presented significant differences in success rates both by logistic regression analysis and variance analysis (P < .05). To minimize the failure of miniscrew implants, proper oral hygiene instruction and effective supervision should be given for patients, especially young (< 12 years) high-angle patients with miniscrew implants placed in the mandible.
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Smoking prevalence, determinants, knowledge, attitudes and habits among Buddhist monks in Lao PDR.
Vanphanom, Sychareun; Phengsavanh, Alongkon; Hansana, Visanou; Menorath, Sing; Tomson, Tanja
2009-06-08
This cross-sectional study, the first of its kind, uses baseline data on smoking prevalence among Buddhist monks in Northern and Central provinces of Lao PDR. Between March and September 2006, 390 monks were interviewed, using questionnaires, to assess smoking prevalence including determinants, knowledge and attitudes. Data entry was performed with Epi-Info (version 6.04) and data analysis with SPSS version 11. Descriptive analysis was employed for all independent and dependent variables. Chi-square or Fisher's exact test were used for categorical variables to compare smoking status, knowledge, attitudes and province. Logistic regression was applied to identify determinants of smoking. Daily current smoking was 11.8%. Controlling for confounding variables, age at start of monkhood and the length of religious education were significant determinants of smoking. The majority of the monks 67.9% were in favor of the idea that offerings of cigarettes should be prohibited and that they should refuse the cigarettes offered to them (30.3%) but, in fact, 34.8% of the monks who were current smokers accepted cigarettes from the public. Some monks were smokers, whilst they, in fact, should be used as non-smoking role models. There was no anti-smoking policy in temples. This needs to be addressed when setting up smoke-free policies at temples.
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Granger, Claire; Spittle, Alicia J; Walsh, Jennifer; Pyman, Jan; Anderson, Peter J; Thompson, Deanne K; Lee, Katherine J; Coleman, Lee; Dagia, Charuta; Doyle, Lex W; Cheong, Jeanie
2018-02-15
To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age. Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables. Two hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables. Histologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.
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Heart period variability and psychopathology in urban boys at risk for delinquency.
Pine, D S; Wasserman, G A; Miller, L; Coplan, J D; Bagiella, E; Kovelenku, P; Myers, M M; Sloan, R P
1998-09-01
To examine associations between heart period variability (HPV) and psychopathology in young urban boys at risk for delinquency, a series of 697-11-year-old younger brothers of adjudicated delinquents received a standardized psychiatric evaluation and an assessment of heart period variability (HPV). Psychiatric symptoms were rated in two domains: externalizing and internalizing psychopathology. Continuous measures of both externalizing and internalizing psychopathology were associated with reductions in HPV components related to parasympathetic activity. These associations could not be explained by a number of potentially confounding variables, such as age, ethnicity, social class, body size, or family history of hypertension. Although familial hypertension predicted reduced HPV and externalizing psychopathology, associations between externalizing psychopathology and HPV were independent of familial hypertension. Psychiatric symptoms are associated with reduced HPV in young urban boys at risk for delinquency.
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Khreis, Haneen; Kelly, Charlotte; Tate, James; Parslow, Roger; Lucas, Karen; Nieuwenhuijsen, Mark
2017-03-01
The question of whether children's exposure to traffic-related air pollution (TRAP) contributes to their development of asthma is unresolved. We conducted a systematic review and performed meta-analyses to analyze the association between TRAP and asthma development in childhood. We systematically reviewed epidemiological studies published until 8 September 2016 and available in the Embase, Ovid MEDLINE (R), and Transport databases. We included studies that examined the association between children's exposure to TRAP metrics and their risk of 'asthma' incidence or lifetime prevalence, from birth to age 18years old. We extracted key characteristics of each included study using a predefined data items template and these were tabulated. We used the Critical Appraisal Skills Programme checklists to assess the validity of each included study. Where four or more independent risk estimates were available for a continuous pollutant exposure, we conducted overall and age-specific meta-analyses, and four sensitivity analyses for each summary meta-analytic exposure-outcome association. Forty-one studies met our eligibility criteria. There was notable variability in asthma definitions, TRAP exposure assessment methods and confounder adjustment. The overall random-effects risk estimates (95% CI) were 1.08 (1.03, 1.14) per 0.5×10 -5 m -1 black carbon (BC), 1.05 (1.02, 1.07) per 4μg/m 3 nitrogen dioxide (NO 2 ), 1.48 (0.89, 2.45) per 30μg/m 3 nitrogen oxides (NO x ), 1.03 (1.01, 1.05) per 1μg/m 3 Particulate Matter <2.5μm in diameter (PM 2.5 ), and 1.05 (1.02, 1.08) per 2μg/m 3 Particulate Matter <10μm in diameter (PM 10 ). Sensitivity analyses supported these findings. Across the main analysis and age-specific analysis, the least heterogeneity was seen for the BC estimates, some heterogeneity for the PM 2.5 and PM 10 estimates and the most heterogeneity for the NO 2 and NO x estimates. The overall risk estimates from the meta-analyses showed statistically significant associations for BC, NO 2 , PM 2.5 , PM 10 exposures and risk of asthma development. Our findings support the hypothesis that childhood exposure to TRAP contributes to their development of asthma. Future meta-analyses would benefit from greater standardization of study methods including exposure assessment harmonization, outcome harmonization, confounders' harmonization and the inclusion of all important confounders in individual studies. PROSPERO 2014: CRD42014015448. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Land-use change and infectious disease in West Africa
NASA Astrophysics Data System (ADS)
Thomson, M. C.; Ericksen, P. J.; Mohamed, A. Ben; Connor, S. J.
Land-use change has been associated with changes in the dynamics of infectious disease in West Africa. Here we describe the complex interactions of land-use change with three diseases (both vector- and non-vector-borne) of considerable public health significance in this region, namely, malaria and irrigation; epidemic meningitis and land degradation; onchocerciasis and deforestation. We highlight the confounding effect of climate variability, which acts as a driver of both land-use change and human health. We conclude, as have others, that the scale of observation always matters, and complex and dynamic feedbacks among social-ecological systems are not easily teased apart. We suggest that in order to establish the causal chain of interactions between land-use change and human health outcomes two approaches are necessary. The first is to have a thorough understanding of the aetiology of disease and the specific mechanisms by which land-use and climate variability affect the transmission of pathogens. This is achieved by focused, detailed studies encompassing a wide range of potential drivers, which are inevitably small scale and often cover short time periods. The second consists of large-scale studies of statistical associations between transmission indices or health outcomes and environmental variables stratified by known ecological or socio-economic confounders, and sufficient in size to overcome local biases in results. Such research activities need to be designed to inform each other if we are to develop predictive models for monitoring these diseases and to develop integrated programs for human health and sustainable land use.
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de Souza, Sara Carolina Scremin; Campanini, Marcela Zambrim; de Andrade, Selma Maffei; González, Alberto Durán; de Melo, Juliana Moura; Mesas, Arthur Eumann
2017-10-01
Although time spent watching television and sleep problems have increased in the last few decades, it is unclear whether these conditions are associated in working adults after controlling for lifestyle, job characteristics and other individual aspects. The present study analyzed the association between time spent watching television and sleep quality among teachers from public schools in Londrina, Brazil. In this cross-sectional study, information from the Pittsburgh Sleep Quality Index (PSQI) and about time spent watching television was obtained during personal interviews. Logistic regression models adjusted by the main confounders (sociodemographic, occupational and lifestyle variables) were used in the analyses. Among the 959 studied teachers (68.2% women, median age: 42years), teachers who watched >120min/day had a higher likelihood of reporting poor sleep quality (PSQI>5) (odds ratio=1.41; 95% confidence interval=1.01; 1.98) compared with those who watched television for up to 60min/day, regardless of gender, age, work hours, leisure time physical activity and other lifestyle variables. This association did not remain significant after the adjustment for health conditions, i.e., obesity, anxiety, depression and chronic pain, which may act as confounding variables in the relationship between watching television and poor sleep quality. Watching television for >120min/day was independently associated with poorer sleep quality, which should be considered in the prevention and treatment of sleep disturbances among working population. Copyright © 2017 Elsevier Inc. All rights reserved.
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Brain tumors in children and occupational exposure of parents.
Peters, F M; Preston-Martin, S; Yu, M C
1981-07-10
Ninety-two cases of brain tumor in children less than 10 years old were compared with 92 matched controls for parental occupational history. Cases were more likely than controls to show material occupations involving chemical exposure, paternal occupations involving solvents, and employment of father in the aircraft industry. These three factors were not affected by adjustment for the potential confounding variables examined in this study.
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Thyroid disorders in older adults.
Visser, W Edward; Visser, Theo J; Peeters, Robin P
2013-06-01
This article summarizes the current literature about serum thyroid parameters and thyroid disease during aging. Changes in thyroid function tests may be part of the physiology of aging, after exclusion of confounding variables. Overt thyroid disease requires immediate treatment. Treatment of subclinical hyperthyroidism in the elderly can be advocated, while watchful waiting may be an appropriate approach for subclinical hypothyroidism. Copyright © 2013 Elsevier Inc. All rights reserved.
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ERIC Educational Resources Information Center
Rodenborn, Leo V., Jr.
The project's purpose was to determine whether attention to the task during testing was a confounding variable in measures of visual perception ability. Samples of 30 perceptually handicapped (PH) and 30 normal subjects (N) were randomly selected from children so classified on the Frostig DTVP, providing they had IQ scores between 85 and 115 on…
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Reducing the Language Content in ToM Tests: A Developmental Scale
ERIC Educational Resources Information Center
Burnel, Morgane; Perrone-Bertolotti, Marcela; Reboul, Anne; Baciu, Monica; Durrleman, Stephanie
2018-01-01
The goal of the current study was to statistically evaluate the reliable scalability of a set of tasks designed to assess Theory of Mind (ToM) without language as a confounding variable. This tool might be useful to study ToM in populations where language is impaired or to study links between language and ToM. Low verbal versions of the ToM tasks…
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Adhikari, Richa; D’Souza, Jennifer; Solimon, Elsayed Z.; Burke, Gregory L.; Daviglus, Martha; Jacobs, David R.; Park, Sung Kyun; Sheppard, Lianne; Thorne, Peter S.; Kaufman, Joel D.; Larson, Timothy V.; Adar, Sara D.
2017-01-01
Background Reduced heart rate variability, a marker of impaired cardiac autonomic function, has been linked to short-term exposure to airborne particles. This research adds to the literature by examining associations with long-term exposures to coarse particles (PM10-2.5). Methods Using electrocardiogram recordings from 2,780 participants (45-84 years) from three Multi-Ethnic Study of Atherosclerosis sites, we assessed the standard deviation of normal-to-normal intervals (SDNN) and root-mean square differences of successive normal-to-normal intervals (rMSSD) at a baseline (2000-2002) and follow-up (2010-2012) examination (mean visits/person=1.5). Annual average concentrations of PM10-2.5 mass, copper, zinc, phosphorus, silicon, and endotoxin were estimated using site-specific spatial prediction models. We assessed associations for baseline heart rate variability and rate of change in heart rate variability over time using multivariable mixed models adjusted for time, sociodemographic, lifestyle, health, and neighborhood confounders, including co-pollutants. Results In our primary models adjusted for demographic and lifestyle factors and site, PM10-2.5 mass was associated with 1.0% (95% CI: -4.1, 2.1%) lower SDNN levels per interquartile range of 2 μg/m3. Stronger associations, however, were observed prior to site adjustment and with increasing residential stablity. Similar patterns were found for rMSSD. We found little evidence for associations with other chemical species and with with the rate of change in heart rate variability, though endotoxin was associated with increasing heart rate variability over time. Conclusion We found only weak evidence that long-term PM10-2.5 exposures are associated with lowered heart rate variability. Stronger associations among residentially stable individuals suggest that confirmatory studies are needed. PMID:27035690
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Tanaka, Masako; Georgiades, Katholiki; Boyle, Michael H; MacMillan, Harriet L
2015-01-01
There is increasing evidence for the adverse effects of child maltreatment on academic performance; however, most of these studies used selective samples and did not account for potential confounding or mediating factors. We examined the relationship between child physical abuse (PA; severe and non-severe) and sexual abuse (SA) and educational attainment (years of education, failure to graduate from high school) with a Canadian community sample. We used data from the Ontario Child Health Study (N = 1,893), a province-wide longitudinal survey. Potential confounding variables (family socio-demographic and parental capacity) and child-level characteristics were assessed in 1983, and child abuse was determined in 2000-2001 based on retrospective self-report. Results showed that PA and SA were associated with several factors indicative of social disadvantage in childhood. Multilevel regression analyses for years of education revealed a significant estimate for severe PA based on the unadjusted model (-0.60 years, 95% CI = [-0.45, -0.76]); estimates for non-severe PA (0.05 years, CI = [-0.15, 0.26]) and SA (-0.25 years, CI = [-0.09, -0.42]) were not significant. In the adjusted full model, the only association to reach significance was between severe PA and reduced years of education (-0.31 years, CI = [-0.18, -0.44]). Multilevel regression analyses for failure to graduate from high school showed significant unadjusted estimates for severe PA (OR = 1.77, 95% CI = [1.21, 2.58]) and non-severe PA (OR = 1.61, CI = [1.01, 2.57]); SA was not associated with this outcome (OR = 1.40, CI = [0.94, 2.07]). In the adjusted full models, there were no significant associations between child abuse variables and failure to graduate. The magnitude of effect of PA on both outcomes was reduced largely by child individual characteristics. These findings generally support earlier research, indicating the adverse effects of child maltreatment on educational attainment. Of particular note, severe PA was associated with reduced years of education after accounting for a comprehensive set of potential confounding variables and child characteristics. © The Author(s) 2014.
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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
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Brunekreef, Bert; Beelen, Rob; Hoek, Gerard; Schouten, Leo; Bausch-Goldbohm, Sandra; Fischer, Paul; Armstrong, Ben; Hughes, Edward; Jerrett, Michael; van den Brandt, Piet
2009-03-01
Evidence is increasing that long-term exposure to ambient air pollution is associated with deaths from cardiopulmonary diseases. In a 2002 pilot study, we reported clear indications that traffic-related air pollution, especially at the local scale, was related to cardiopulmonary mortality in a randomly selected subcohort of 5000 older adults participating in the ongoing Netherlands Cohort Study (NLCS) on diet and cancer. In the current study, referred to as NLCS-AIR, our objective was to obtain more precise estimates of the effects of traffic-related air pollution by analyzing associations with cause-specific mortality, as well as lung cancer incidence, in the full cohort of approximately 120,000 subjects. Cohort members were 55 to 69 years of age at enrollment in 1986. Follow-up was from 1987 through 1996 for mortality (17,674 deaths) and from late 1986 through 1997 for lung cancer incidence (2234 cases). Information about potential confounding variables and effect modifiers was available from the questionnaire that subjects completed at enrollment and from publicly available data (including neighborhood-scale information such as income distributions). The NLCS was designed for a case-cohort approach, which makes use of all the cases in the full cohort, while data for the random subcohort are used to estimate person-time experience in the study. Full information on confounders was available for the subjects in the random subcohort and for the emerging cases of mortality and lung cancer incidence during the follow-up period, and in NLCS-AIR we used the case-cohort approach to examine the relation between exposure to air pollution and cause-specific mortality and lung cancer. We also specified a standard Cox proportional hazards model within the full cohort, for which information on potential confounding variables was much more limited. Exposure to air pollution was estimated for the subjects' home addresses at baseline in 1986. Concentrations were estimated for black smoke (a simple marker for soot) and nitrogen dioxide (NO2) as indicators of traffic-related air pollution, as well as nitric oxide (NO), sulfur dioxide (SO2), and particulate matter with aerodynamic diameter < or = 2.5 microm (PM2.5), as estimated from measurements of particulate matter with aerodynamic diameter < or = 10 microm (PM10). Overall long-term exposure concentrations were considered to be a function of air pollution contributions at regional, urban, and local scales. We used interpolation from data obtained routinely at regional stations of the National Air Quality Monitoring Network (NAQMN) to estimate the regional component of exposure at the home address. Average pollutant concentrations were estimated from NAQMN measurements for the period 1976 through 1996. Land-use regression methods were used to estimate the urban exposure component. For the local exposure component, geographic information systems (GISs) were used to generate indicators of traffic exposure that included traffic intensity on and distance to nearby roads. A major effort was made to collect traffic intensity data from individual municipalities. The exposure variables were refined considerably from those used in the pilot study, but we also analyzed the data for the full cohort in the current study using the exposure indicators of the pilot study. We analyzed the data in models with the estimated overall pollutant concentration as a single variable and with the background concentration (the sum of regional and urban components) and the local exposure estimate from traffic indicators as separate variables. In the full-cohort analyses adjusted for the limited set of confounders, estimated overall exposure concentrations of black smoke, NO2, NO, and PM2.5 were associated with mortality. For a 10-microg/m3 increase in the black smoke concentration, the relative risk (RR) (95% confidence interval [CI]) was 1.05 (1.00-1.11) for natural-cause (nonaccidental) mortality, 1.04 (0.95-1.13) for cardiovascular mortality, 1.22 (0.99-1.50) for respiratory mortality, 1.03 (0.88-1.20) for lung cancer mortality, and 1.04 (0.97-1.12) for noncardiopulmonary, non-lung cancer mortality. Results were similar for NO2, NO, and PM2.5. For a 10-microg/m3 increase in PM2.5 concentration, the RR for natural-cause mortality was 1.06 (95% CI, 0.97-1.16), the same as in the results of the American Cancer Society Study reported by Pope and colleagues in 2002. The highest relative risks were found for respiratory mortality, though confidence intervals were wider for this less-frequent cause of death. No associations with mortality were found for SO2. Some of the associations between the traffic indicator variables used to assess traffic intensity near the home and mortality reached statistical significance in the full cohort. For an increase in traffic intensity of 10,000 motor vehicles in 24 hours (motor vehicles/day) on the road nearest a subject's residence, the RR was 1.03 (95% CI, 1.00-1.08) for natural-cause mortality, 1.05 (0.99-1.12) for cardiovascular mortality, 1.10 (0.95-1.26) for respiratory mortality, 1.07 (0.96-1.19) for lung cancer mortality, and 1.00 (0.94-1.06) for noncardiopulmonary, non-lung cancer mortality. Results were similar for traffic intensity in a 100-m buffer around the subject's residence and living near a major road (a road with more than 10,000 motor vehicles/day). Distance in meters to the nearest major road and traffic intensity on the nearest major road were not associated with any of the mortality outcomes. We did not find an association between cardiopulmonary mortality and living near a major road as defined using the methods of the pilot study. In the case-cohort analyses adjusted for all potential confounders, we found no associations between background air pollution and mortality. The associations between traffic intensity and mortality were weaker than in the full cohort, and confidence intervals were wider, consistent with the smaller number of subjects. The lower relative risks of mortality associated with traffic variables in the case-cohort study population could be related to the particular subcohort that was randomly selected from the full cohort, as the risks estimated with the actual subcohort were well below the average estimates obtained for 100 new case-cohort analyses with 100 alternative subcohorts of 5000 subjects each that we randomly selected from the full cohort. Differences in adjusted relative risks between the full-cohort and the case-cohort analyses could be explained by random error introduced by sampling from the full cohort and by a selection effect resulting from the relatively large number of missing data for variables in the extensive confounder model used in the case-cohort analyses. More complete control for confounding probably did not contribute much to the lower relative risks in the case-cohort analyses, especially for the traffic variables, as results were similar when the limited confounder model for the full cohort was used in analyses of the subjects in the case-cohort study population. In additional analyses using black smoke concentrations as the exposure variables, we found that the association between overall black smoke and cardiopulmonary mortality was somewhat stronger for case-cohort subjects who did not change residence during follow-up, and in the full cohort, there was a tendency for relative risks to be higher for subjects living in the three major cities included in the study. Adjustment for estimated exposure to traffic noise did not affect the associations of background black smoke and traffic intensity with cardiovascular mortality. There was some indication of an association between traffic noise and cardiovascular mortality only for the 1.6% of the subjects in the full cohort who were exposed to traffic noise in the highest category of > 65 A-weighted decibels (dB(A); decibels with the sound pressure scale adjusted to conform with the frequency response of the human ear). Examination of sex, smoking status, educational level, and vegetable and fruit intake as possible effect modifiers showed that for overall black smoke concentrations, associations with mortality tended to be stronger in case-cohort subjects with lower levels of education and those with low fruit intake, but differences between strata were not statistically significant. For lung cancer incidence, we found essentially no relation to exposure to NO2, black smoke, PM2.5, SO2, or several traffic indicators. Associations of overall air pollution concentrations and traffic indicator variables with lung cancer incidence were, however, found in subjects who had never smoked, with an RR of 1.47 (95% CI, 1.01-2.16) for a 10-microg/m3 increase in overall black smoke concentration. In the current study, the mortality risks associated with both background air pollution and traffic exposure variables were much smaller than the estimate previously reported in the pilot study for risk of cardiopulmonary mortality associated with living near a major road (RR, 1.95; 95% CI, 1.09-3.51). The differences are most likely due to the extension of the follow-up period in the current study and to random error in the pilot study related to sampling from the full cohort. Though relative risks were generally small in the current study, long-term average concentrations of black smoke, NO2, and PM2.5 were related to mortality, and associations of black smoke and NO2 exposure with natural-cause and respiratory mortality were statistically significant. Traffic intensity near the home was also related to natural-cause mortality. The highest relative risks associated with background air pollution and traffic variables were for respiratory mortality, though the number of deaths was smaller than for the other mortality categories. (ABSTRACT TRUNCATED)
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Chee, H; Rampal, K
2003-01-01
Aims: To determine the relation between sick leave and selected exposure variables among women semiconductor workers. Methods: This was a cross sectional survey of production workers from 18 semiconductor factories. Those selected had to be women, direct production operators up to the level of line leader, and Malaysian citizens. Sick leave and exposure to physical and chemical hazards were determined by self reporting. Three sick leave variables were used; number of sick leave days taken in the past year was the variable of interest in logistic regression models where the effects of age, marital status, work task, work schedule, work section, and duration of work in factory and work section were also explored. Results: Marital status was strongly linked to the taking of sick leave. Age, work schedule, and duration of work in the factory were significant confounders only in certain cases. After adjusting for these confounders, chemical and physical exposures, with the exception of poor ventilation and smelling chemicals, showed no significant relation to the taking of sick leave within the past year. Work section was a good predictor for taking sick leave, as wafer polishing workers faced higher odds of taking sick leave for each of the three cut off points of seven days, three days, and not at all, while parts assembly workers also faced significantly higher odds of taking sick leave. Conclusion: In Malaysia, the wafer fabrication factories only carry out a limited portion of the work processes, in particular, wafer polishing and the processes immediately prior to and following it. This study, in showing higher illness rates for workers in wafer polishing compared to semiconductor assembly, has implications for the governmental policy of encouraging the setting up of wafer fabrication plants with the full range of work processes. PMID:12660374
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Diagnostics for Confounding of Time-varying and Other Joint Exposures.
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.
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A Pilot Study of Gait Function in Farmworkers in Eastern North Carolina.
Nguyen, Ha T; Kritchevsky, Stephen B; Foxworth, Judy L; Quandt, Sara A; Summers, Phillip; Walker, Francis O; Arcury, Thomas A
2015-01-01
Farmworkers endure many job-related hazards, including fall-related work injuries. Gait analysis may be useful in identifying potential fallers. The goal of this pilot study was to explore differences in gait between farmworkers and non-farmworkers. The sample included 16 farmworkers and 24 non-farmworkers. Gait variables were collected using the portable GAITRite system, a 16-foot computerized walkway. Generalized linear regression models were used to examine group differences. All models were adjusted for two established confounders, age and body mass index. There were no significant differences in stride length, step length, double support time, and base of support; but farmworkers had greater irregularity of stride length (P = .01) and step length (P = .08). Farmworkers performed significantly worse on gait velocity (P = .003) and cadence (P < .001) relative to non-farmworkers. We found differences in gait function between farmworkers and non-farmworkers. These findings suggest that measuring gait with a portable walkway system is feasible and informative in farmworkers and may possibly be of use in assessing fall risk.
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Anderson, Brenna L; Simhan, Hyagriv N; Simons, Kathryn M; Wiesenfeld, Harold C
2007-06-01
The objective of the study was to determine the frequency of adverse pregnancy outcomes in women with untreated asymptomatic group B beta-hemolytic streptococcal (GBS) bacteriuria during pregnancy. In this retrospective cohort, all women with antepartum GBS bacteriuria in a research registry were included. Controls were women with negative urine cultures. The frequency of chorioamnionitis was compared between groups. Chorioamnionitis was defined as intrapartum fever, fetal tachycardia, and histologic inflammation of the membranes. One hundred twenty-two women with bacteriuria (study group) and 183 women with negative antepartum cultures (controls) were included. There were no differences in demographic characteristics between the groups. Thirty-one women (10.2%) had chorioamnionitis. Untreated GBS bacteriuria was associated with chorioamnionitis after controlling for confounding variables, adjusted odds ratio 7.2 (95% confidence interval 2.4 to 21.2). There was also a significant positive rank correlation between increasing colony count of GBS bacteriuria and increasing grade of chorioamnionitis (P = .02). Untreated antepartum GBS bacteriuria is associated with chorioamnionitis.
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Lewis, Tené T; Cogburn, Courtney D; Williams, David R
2015-01-01
Over the past two decades, research examining the impact of self-reported experiences of discrimination on mental and physical health has increased dramatically. Studies have found consistent associations between exposure to discrimination and a wide range of Diagnostic and Statistical Manual of Mental Disorders (DSM)-diagnosed mental disorders as well as objective physical health outcomes. Associations are seen in cross-sectional as well as longitudinal studies and persist even after adjustment for confounding variables, including personality characteristics and other threats to validity. However, controversies remain, particularly around the best approach to measuring experiences of discrimination, the significance of racial/ethnic discrimination versus overall mistreatment, the need to account for "intersectionalities," and the importance of comprehensive assessments. These issues are discussed in detail, along with emerging areas of emphasis including cyber discrimination, anticipatory stress or vigilance around discrimination, and interventions with potential to reduce the negative effects of discrimination on health. We also discuss priorities for future research and implications for interventions and policy.
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Costa de Oliveira Forkert, E; de Moraes, A C F; Carvalho, H B; Kafatos, A; Manios, Y; Sjöström, M; González-Gross, M; Gottrand, F; Beghin, L; Censi, L; Kersting, M; Moreno, L A
2017-04-01
Socioeconomic status has been associated with obesity in children and adolescents. This association may be dependent according with where adolescents lives. The aim of this study was to evaluate the association between different socioeconomic indicators such as parental education and occupation and socioeconomic status with abdominal obesity in adolescents from two observational studies: the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study (HELENA-CSS) and the Brazilian Cardiovascular Adolescent Health (BRACAH) study. European (n = 3192, aged 12.5-17.5 years, with 53.1% girls from HELENA-CSS) and Brazilian (n = 991, aged 14-18 years, with 54.5% girls from BRACAH study) adolescents from two cross-sectional studies were included in this analysis. Complete data on waist circumference (WC), height, socioeconomic status indicators and several confounders were collected. Socioeconomic indicators were measured using a self-reported questionnaire in order to assess the family social status of the adolescents. Multilevel linear regression models were used to examine associations, and results were adjusted for potential confounders. Adjusted results showed inverse associations between mother's and father's education levels (p < 0.001) and father's occupation level (p < 0.001) with waist-to-height ratio (WHtR) and WC in HELENA-CSS girls. Similarly in European girls, socioeconomic indicators by socioeconomic status and maternal occupation level were associated with WHtR. In HELENA-CSS boys, the same significant association was found between WHtR and WC with maternal occupation level. Moreover, in European boys WHtR was also associated with parental education. In Brazilian adolescents, both indicators of abdominal obesity did not remain associated with the independents variables, after adjustment for potential confounders. Abdominal obesity was associated with socioeconomic indicators in higher-income countries, but this association was not observed in a lower-middle-income country. © 2016 World Obesity Federation.
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Kendal, Adrian R; Prieto-Alhambra, Daniel; Arden, Nigel K; Judge, Andrew
2013-01-01
Objectives To compare 10 year mortality rates among patients undergoing metal-on-metal hip resurfacing and total hip replacement in England. Design Retrospective cohort study. Setting English hospital episode statistics database linked to mortality records from the Office for National Statistics. Population All adults who underwent primary elective hip replacement for osteoarthritis from April 1999 to March 2012. The exposure of interest was prosthesis type: cemented total hip replacement, uncemented total hip replacement, and metal-on-metal hip resurfacing. Confounding variables included age, sex, Charlson comorbidity index, rurality, area deprivation, surgical volume, and year of operation. Main outcome measures All cause mortality. Propensity score matching was used to minimise confounding by indication. Kaplan-Meier plots estimated the probability of survival up to 10 years after surgery. Multilevel Cox regression modelling, stratified on matched sets, described the association between prosthesis type and time to death, accounting for variation across hospital trusts. Results 7437 patients undergoing metal-on-metal hip resurfacing were matched to 22 311 undergoing cemented total hip replacement; 8101 patients undergoing metal-on-metal hip resurfacing were matched to 24 303 undergoing uncemented total hip replacement. 10 year rates of cumulative mortality were 271 (3.6%) for metal-on-metal hip resurfacing versus 1363 (6.1%) for cemented total hip replacement, and 239 (3.0%) for metal-on-metal hip resurfacing versus 999 (4.1%) for uncemented total hip replacement. Patients undergoing metal-on-metal hip resurfacing had an increased survival probability (hazard ratio 0.51 (95% confidence interval 0.45 to 0.59) for cemented hip replacement; 0.55 (0.47 to 0.65) for uncemented hip replacement). There was no evidence for an interaction with age or sex. Conclusions Patients with hip osteoarthritis undergoing metal-on-metal hip resurfacing have reduced mortality in the long term compared with those undergoing cemented or uncemented total hip replacement. This difference persisted after extensive adjustment for confounding factors available in our data. The study results can be applied to matched populations, which exclude patients who are very old and have had complex total hip replacements. Although residual confounding is possible, the observed effect size is large. These findings require validation in external cohorts and randomised clinical trials. PMID:24284336
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Assessing the determinants of evolutionary rates in the presence of noise.
Plotkin, Joshua B; Fraser, Hunter B
2007-05-01
Although protein sequences are known to evolve at vastly different rates, little is known about what determines their rate of evolution. However, a recent study using principal component regression (PCR) has concluded that evolutionary rates in yeast are primarily governed by a single determinant related to translation frequency. Here, we demonstrate that noise in biological data can confound PCRs, leading to spurious conclusions. When equalizing noise levels across 7 predictor variables used in previous studies, we find no evidence that protein evolution is dominated by a single determinant. Our results indicate that a variety of factors--including expression level, gene dispensability, and protein-protein interactions--may independently affect evolutionary rates in yeast. More accurate measurements or more sophisticated statistical techniques will be required to determine which one, if any, of these factors dominates protein evolution.
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An R package for state-trace analysis.
Prince, Melissa; Hawkins, Guy; Love, Jonathon; Heathcote, Andrew
2012-09-01
State-trace analysis (Bamber, Journal of Mathematical Psychology, 19, 137-181, 1979) is a graphical analysis that can determine whether one or more than one latent variable mediates an apparent dissociation between the effects of two experimental manipulations. State-trace analysis makes only ordinal assumptions and so, is not confounded by range effects that plague alternative methods, especially when performance is measured on a bounded scale (such as accuracy). We describe and illustrate the application of a freely available GUI driven package, StateTrace, for the R language. StateTrace automates many aspects of a state-trace analysis of accuracy and other binary response data, including customizable graphics and the efficient management of computationally intensive Bayesian methods for quantifying evidence about the outcomes of a state-trace experiment, developed by Prince, Brown, and Heathcote (Psychological Methods, 17, 78-99, 2012).
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Twentieth century warming of the tropical Atlantic captured by Sr-U paleothermometry
NASA Astrophysics Data System (ADS)
Alpert, Alice E.; Cohen, Anne L.; Oppo, Delia W.; DeCarlo, Thomas M.; Gaetani, Glenn A.; Hernandez-Delgado, Edwin A.; Winter, Amos; Gonneea, Meagan E.
2017-02-01
Coral skeletons are valuable archives of past ocean conditions. However, interpretation of coral paleotemperature records is confounded by uncertainties associated with single-element ratio thermometers, including Sr/Ca. A new approach, Sr-U, uses U/Ca to constrain the influence of Rayleigh fractionation on Sr/Ca. Here we build on the initial Pacific Porites Sr-U calibration to include multiple Atlantic and Pacific coral genera from multiple coral reef locations spanning a temperature range of 23.15-30.12°C. Accounting for the wintertime growth cessation of one Bermuda coral, we show that Sr-U is strongly correlated with the average water temperature at each location (r2 = 0.91, P < 0.001, n = 19). We applied the multispecies spatial calibration between Sr-U and temperature to reconstruct a 96 year long temperature record at Mona Island, Puerto Rico, using a coral not included in the calibration. Average Sr-U derived temperature for the period 1900-1996 is within 0.12°C of the average instrumental temperature at this site and captures the twentieth century warming trend of 0.06°C per decade. Sr-U also captures the timing of multiyear variability but with higher amplitude than implied by the instrumental data. Mean Sr-U temperatures and patterns of multiyear variability were replicated in a second coral in the same grid box. Conversely, Sr/Ca records from the same two corals were inconsistent with each other and failed to capture absolute sea temperatures, timing of multiyear variability, or the twentieth century warming trend. Our results suggest that coral Sr-U paleothermometry is a promising new tool for reconstruction of past ocean temperatures.
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Twentieth century warming of the tropical Atlantic captured by Sr-U paleothermometry
Alpert, Alice E.; Cohen, Anne L.; Oppo, Delia W.; DeCarlo, Thomas M.; Gaetani, Glenn A.; Hernandez-Delgado, Edwin A.; Winter, Amos; Gonneea, Meagan
2017-01-01
Coral skeletons are valuable archives of past ocean conditions. However, interpretation of coral paleotemperature records is confounded by uncertainties associated with single-element ratio thermometers, including Sr/Ca. A new approach, Sr-U, uses U/Ca to constrain the influence of Rayleigh fractionation on Sr/Ca. Here we build on the initial Pacific Porites Sr-U calibration to include multiple Atlantic and Pacific coral genera from multiple coral reef locations spanning a temperature range of 23.15–30.12°C. Accounting for the wintertime growth cessation of one Bermuda coral, we show that Sr-U is strongly correlated with the average water temperature at each location (r2 = 0.91, P < 0.001, n = 19). We applied the multispecies spatial calibration between Sr-U and temperature to reconstruct a 96 year long temperature record at Mona Island, Puerto Rico, using a coral not included in the calibration. Average Sr-U derived temperature for the period 1900–1996 is within 0.12°C of the average instrumental temperature at this site and captures the twentieth century warming trend of 0.06°C per decade. Sr-U also captures the timing of multiyear variability but with higher amplitude than implied by the instrumental data. Mean Sr-U temperatures and patterns of multiyear variability were replicated in a second coral in the same grid box. Conversely, Sr/Ca records from the same two corals were inconsistent with each other and failed to capture absolute sea temperatures, timing of multiyear variability, or the twentieth century warming trend. Our results suggest that coral Sr-U paleothermometry is a promising new tool for reconstruction of past ocean temperatures.
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Rubin, Samuel J; Kirke, Diana N; Ezzat, Waleed H; Truong, Minh T; Salama, Andrew R; Jalisi, Scharukh
Determine whether marital status is a significant predictor of survival in human papillomavirus-positive oropharyngeal cancer. A single center retrospective study included patients diagnosed with human papilloma virus-positive oropharyngeal cancer at Boston Medical Center between January 1, 2010 and December 30, 2015, and initiated treatment with curative intent at Boston Medical Center. Demographic data and tumor-related variables were recorded. Univariate analysis was performed using a two-sample t-test, chi-squared test, Fisher's exact test, and Kaplan Meier curves with a log rank test. Multivariate survival analysis was performed using a Cox regression model. A total of 65 patients were included in the study with 24 patients described as married and 41 patients described as single. There was no significant difference in most demographic variables or tumor related variables between the two study groups, except single patients were significantly more likely to have government insurance (p=0.0431). Furthermore, there was no significant difference in 3-year overall survival between married patients and single patients (married=91.67% vs single=87.80%; p=0.6532) or 3-year progression free survival (married=79.17% vs single=85.37%; p=0.8136). After adjusting for confounders including age, sex, race, insurance type, smoking status, treatment, and AJCC combined pathologic stage, marital status was not a significant predictor of survival [HR=0.903; 95% CI (0.126,6.489); p=0.9192]. Although previous literature has demonstrated that married patients with head and neck cancer have a survival benefit compared to single patients with head and neck cancer, we were unable to demonstrate the same survival benefit in a cohort of patients with human papilloma virus-positive oropharyngeal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.
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Luijendijk, Hendrika J; de Bruin, Niels C; Hulshof, Tessa A; Koolman, Xander
2016-02-01
Numerous large observational studies have shown an increased risk of mortality in elderly users of conventional antipsychotics. Health authorities have warned against use of these drugs. However, terminal illness is a potentially strong confounder of the observational findings. So, the objective of this study was to systematically assess whether terminal illness may have biased the observational association between conventional antipsychotics and risk of mortality in elderly patients. Studies were searched in PubMed, CINAHL, Embase, the references of selected studies and articles referring to selected studies (Web of Science). Inclusion criteria were (i) observational studies that estimated (ii) the risk of all-cause mortality in (iii) new elderly users of (iv) conventional antipsychotics compared with atypical antipsychotics or no use. Two investigators assessed the characteristics of the exposure and reference groups, main results, measured confounders and methods used to adjust for unmeasured confounders. We identified 21 studies. All studies were based on administrative medical and pharmaceutical databases. Sicker and older patients received conventional antipsychotics more often than new antipsychotics. The risk of dying was especially high in the first month of use, and when haloperidol was administered per injection or in high doses. Terminal illness was not measured in any study. Instrumental variables that were used were also confounded by terminal illness. We conclude that terminal illness has not been adjusted for in observational studies that reported an increased risk of mortality risk in elderly users of conventional antipsychotics. As the validity of the evidence is questionable, so is the warning based on it. Copyright © 2015 John Wiley & Sons, Ltd.
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Meat consumption, meat cooking and risk of lung cancer among Uruguayan men.
De Stefani, Eduardo; Ronco, Alvaro L; Boffetta, Paolo; Deneo-Pellegrini, Hugo; Acosta, Gisele; Mendilaharsu, María
2010-01-01
A case-control study was conducted in Uruguay, including 876 male cases of lung cancer and 876 male hospitalized controls, frequency matched for age (ten-year intervals), residence and hospital. The following explanatory variables were included in the study: fried red meat, barbecued red meat, boiled red meat, and salted red meat. These items were log transformed and energy-adjusted by the residuals method. The following potential confounders were included into the models: age, residence, hospital, education, family history of lung cancer, body mass index, smoking index, alcohol drinking, mate consumption, total energy intake, non-meat fatty foods and total fruits. The main objective was to estimate the odds ratios associated with lung cancer risk. Whereas fried meat, barbecued meat, and salted meat were positively associated with risk (OR of the highest quartile of salted meat versus the lowest, 2.90, 95 % CI 1.99-4.25, p-value for trend<0.0001), boiled red meat was mainly protective. We conclude that salted meat was the main risk factor. The mechanisms could be related to the content of N-nitroso compounds in salted meat.
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Striatal action-value neurons reconsidered.
Elber-Dorozko, Lotem; Loewenstein, Yonatan
2018-05-31
It is generally believed that during economic decisions, striatal neurons represent the values associated with different actions. This hypothesis is based on studies, in which the activity of striatal neurons was measured while the subject was learning to prefer the more rewarding action. Here we show that these publications are subject to at least one of two critical confounds. First, we show that even weak temporal correlations in the neuronal data may result in an erroneous identification of action-value representations. Second, we show that experiments and analyses designed to dissociate action-value representation from the representation of other decision variables cannot do so. We suggest solutions to identifying action-value representation that are not subject to these confounds. Applying one solution to previously identified action-value neurons in the basal ganglia we fail to detect action-value representations. We conclude that the claim that striatal neurons encode action-values must await new experiments and analyses. © 2018, Elber-Dorozko et al.
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Marinaccio, Alessandro; Belli, Stefano; Binazzi, Alessandra; Scarselli, Alberto; Massari, Stefania; Bruni, Antonella; Conversano, Michele; Crosignani, Paolo; Minerba, Aldo; Zona, Amerigo; Comba, Pietro
2011-01-01
The association between cancer incidence and the residence near polluting facilities in an industrial area nearby Taranto has been investigated. Age, sex and occupational exposure were controlled as confounding variables in a case-control study (658 cases, 2092 controls). High risks were evidenced close to the steel mill (OR: 3.54), coke plant (OR: 4.80), mineral deposit (OR: 3.33) and shipbuilding (OR: 4.29) for pleural neoplasm, and to the steel mill (OR: 1.65) and shipbuilding (OR: 1.79) for lung cancer. After adjustment for occupational exposure, increasing trends of risk were observed both for lung and bladder cancers. Cancer risks were evidenced near industrial sites and the introduction of "occupational exposure" as a confounder modified significantly the risks with respect to distance from the source of pollution, particularly for pleural, lung and bladder cancers.
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Baldock, Deanna; Miller, Justin B; Leger, Gabriel C; Banks, Sarah Jane
2016-01-01
Patients with frontotemporal dementia (FTD) typically have initial deficits in language or changes in personality, while the defining characteristic of Alzheimer's disease (AD) is memory impairment. Neuropsychological findings in the two diseases tend to differ, but can be confounded by verbal impairment in FTD impacting performance on memory tests in these patients. Twenty-seven patients with FTD and 102 patients with AD underwent a neuropsychological assessment before diagnosis. By utilizing analogous versions of a verbal and nonverbal memory test, we demonstrated differences in these two modalities between AD and FTD. Better differentiation between AD and FTD is found in a nonverbal memory test, possibly because it eliminates the confounding variable of language deficits found in patients with FTD. These results highlight the importance of nonverbal learning tests with multiple learning trials in diagnostic testing.
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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.
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Venteris, E.R.; McCarty, G.W.; Ritchie, J.C.; Gish, T.
2004-01-01
Controlled studies to investigate the interaction between crop growth, soil properties, hydrology, and management practices are common in agronomy. These sites (much as with real world farmland) often have complex management histories and topographic variability that must be considered. In 1993 an interdisiplinary study was started for a 20-ha site in Beltsville, MD. Soil cores (271) were collected in 1999 in a 30-m grid (with 5-m nesting) and analyzed as part of the site characterization. Soil organic carbon (SOC) and 137Cesium (137Cs) were measured. Analysis of aerial photography from 1992 and of farm management records revealed that part of the site had been maintained as a swine pasture and the other portion as cropped land. Soil properties, particularly soil redistribution and SOC, show large differences in mean values between the two areas. Mass C is 0.8 kg m -2 greater in the pasture area than in the cropped portion. The pasture area is primarily a deposition site, whereas the crop area is dominated by erosion. Management influence is suggested, but topographic variability confounds interpretation. Soil organic carbon is spatially structured, with a regionalized variable of 120 m. 137Cs activity lacks spatial structure, suggesting disturbance of the profile by animal activity and past structures such as swine shelters and roads. Neither SOC nor 137Cs were strongly correlated to terrain parameters, crop yields, or a seasonal soil moisture index predicted from crop yields. SOC and 137Cs were weakly correlated (r2 ???0.2, F-test P-value 0.001), suggesting that soil transport controls, in part, SOC distribution. The study illustrates the importance of past site history when interpreting the landscape distribution of soil properties, especially those strongly influenced by human activity. Confounding variables, complex soil hydrology, and incomplete documentation of land use history make definitive interpretations of the processes behind the spatial distributions difficult. Such complexity may limit the accuracy of scaling approaches to mapping SOC and soil redistribution.
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Exploratory reconstructability analysis of accident TBI data
NASA Astrophysics Data System (ADS)
Zwick, Martin; Carney, Nancy; Nettleton, Rosemary
2018-02-01
This paper describes the use of reconstructability analysis to perform a secondary study of traumatic brain injury data from automobile accidents. Neutral searches were done and their results displayed with a hypergraph. Directed searches, using both variable-based and state-based models, were applied to predict performance on two cognitive tests and one neurological test. Very simple state-based models gave large uncertainty reductions for all three DVs and sizeable improvements in percent correct for the two cognitive test DVs which were equally sampled. Conditional probability distributions for these models are easily visualized with simple decision trees. Confounding variables and counter-intuitive findings are also reported.
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Morsi, Rami Z; Safa, Rawan; Baroud, Serge F; Fawaz, Cherine N; Farha, Jad I; El-Jardali, Fadi; Chaaya, Monique
2017-04-11
Since July 2015, Lebanon has been experiencing a waste management crisis. Dumpsites in inhabited areas and waste burning have emerged due to the waste accumulation, further adding to the gravity of the situation. However, the association between the crisis and health of the population has not been scientifically reported. A comparative cross-sectional study was conducted to assess whether exposure to open dumpsites and waste burning is associated with acute health symptoms. The study sample included 221 male workers between the ages of 18-60 years selected from two areas chosen based on their proximity to a garbage dumpsite and waste burning. 110 workers were exposed to a garbage dumpsite and waste burning, and 111 workers were not. Data were collected via a face-to-face interview using a newly developed validated structured questionnaire. Chi-square tests were used to check for statistically significant differences between exposure and covariates. Multivariable analyses using multiple logistic regression were used to compare health symptoms between exposed and unexposed workers adjusting for potential confounders. The prevalence of acute health symptoms was greater among the exposed workers than the non-exposed workers, including gastrointestinal, respiratory, dermatological and constitutional symptoms. Controlling for confounding variables, such as age, insurance, family support, residence near dumpsite, work site, and smoking, a minimum odds ratio (OR) of 4.30 was obtained when comparing the exposed population to those non-exposed. The strong association between improper waste management and physical health calls for immediate attention by the government, stakeholders and community members to find optimal solutions for this waste management crisis and set immediate priority interventions such as regular waste collection, volume reduction and recycling performance improvement. However, the long recall period may have underestimated our results.
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Munger, R.; Isacson, P.; Hu, S.; Burns, T.; Hanson, J.; Lynch, C.F.; Cherryholmes, K.; Van Dorpe, P.; Hausler, W.J.
1997-01-01
In a statewide survey of 856 Iowa municipal drinking water supplies in 1986-1987 the Rathbun rural water system was found to contain elevated levels of triazine herbicides. Rates of low birth weight, prematurity, and intrauterine growth retardation (IUGR) in live singleton births during the period 1984-1990 by women living in 13 communities served by the Rathbun water system were compared to other communities of similar size in the same Iowa counties. The Rathbun communities had a greater risk of IUGR than southern Iowa communities with other surface sources of drinking water (relative risk = 1.8; 95% CI = 1.3, 2.7). Multiple linear regression analyses revealed that levels of the herbicides atrazine, metolachlor, and cyanazine were each significant predictors of community IUGR rates in southern Iowa after controlling for several potentially confounding factors including maternal smoking and socioeconomic variables. The association with IUGR was strongest for atrazine, but all three herbicides were intercorrelated and the independent contributions of each to IUGR risk could not be determined. We conclude that communities in southern Iowa with drinking water supplies contaminated with herbicides have elevated rates of IUGR compared to neighboring communities with different water supplies. Because of the limitations of the ecologic design of this study, including aggregate rather than individual measures of exposure and limited ability to control for confounding factors related to source of drinking water and risk of IUGR, a strong causal relationship between any specific water contaminant and risk of IUGR cannot yet be inferred. The association between the water supplied to the Rathbun communities and the increased risk of IUGR should be considered a preliminary finding that needs to be verified by more detailed epidemiologic studies.
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Pregnancy context and women's health-related quality of life.
Gariepy, Aileen; Lundsberg, Lisbet S; Vilardo, Nicole; Stanwood, Nancy; Yonkers, Kimberly; Schwarz, Eleanor B
2017-05-01
The objective was to quantify the association of pregnancy context and health-related quality of life (HRQoL). English- or Spanish-speaking women, aged 16-44, with pregnancies <24 weeks' gestation were enrolled in this cross-sectional study between June 2014 and June 2015. Participants completed self-assessments of pregnancy "context," including timing, intention, wantedness, desirability, happiness, and planning (measured with the London Measure of Unplanned Pregnancy). HRQoL was measured using the Patient Reported Outcomes Measurement Information System Global Short Form. Associations between measures of pregnancy context and HRQoL scores in the lowest tertile were examined using multivariable logistic regression to adjust for potential confounding variables. We enrolled 161 participants (mean age=27.2±6.6 years). Only 14% self-identified as White, non-Hispanic; 42% Hispanic; 37% Black, non-Hispanic; and 7% multiracial. Most (79%) participants were unmarried, and 75% were parenting. Mean gestational age was 9±4.6 weeks. In unadjusted models, women reporting mixed feelings about wanting to have a baby, an undesired pregnancy or feeling unhappy about learning of their pregnancy more frequently had low mental and physical HRQoL compared to women reporting wanted, desired, happy pregnancies. Women with an unplanned pregnancy or pregnancy occurring at the wrong time also had lower physical HRQoL than women reporting pregnancies that were planned or happened at the right time. However, after multivariate adjustment, including history of depression, pregnancy contexts were not associated with low mental or physical HRQoL. After adjusting for multiple confounders, pregnancy context is not significantly associated with HRQoL. The focus on pregnancy intention in public health programs may not sufficiently assess multidimensional aspects of pregnancy context and may not align with patient-centered outcomes such as HRQoL. Copyright © 2017 Elsevier Inc. All rights reserved.
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Caqueo-Urízar, Alejandra; Fond, Guillaume; Urzúa, Alfonso; Boyer, Laurent; Williams, David R
2016-12-01
The aim of the present study was (i) to assess the prevalence of Violent Behavior in Schizophrenia (VBS) in a sample of community-dwelling outpatients in three middle-income countries of Latin America and (ii) to determine the clinical and socio-demographical risk factors associated with VBS and aggression level. The study included 253 stabilized outpatients with schizophrenia and their principal caregivers from 3 public ambulatory psychiatric care centers in Bolivia (N=83), Chile (N=85), and Peru (N=85). VBS was defined according to the Overt Aggression Scale (OAS) score and the aggression level was measured by the aggression subscore of the Agitated Behavior Scale of Corrigan. We collected socio-demographic information and clinical data. Multiple linear and logistic regressions were performed to determine which variables were associated with VBS and aggression level. The prevalence of VBS differed statistically between the three countries (p<0.001) with 3.5% in Chile, 14.6% in Peru and 55.4% in Bolivia. After adjustment for confounding factors, VBS was associated with a younger age, a more severe psychotic symptomatology, a lower family income and unemployment. After adjustment for confounding factors, aggression level was associated with a more severe psychotic symptomatology, a lower family income, a younger age at illness onset and higher number of hospitalizations in the last 3years. These results may guide future health policies to specifically provide social support and rehabilitation care to VBS patients in middle-income countries, including psychoeducation and a more integrated work between the treating medical team and the social workers. Copyright © 2016 Elsevier B.V. All rights reserved.
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Shai, Daniel; Shoham-Vardi, Ilana; Amsalem, Doron; Silverberg, Daniel; Levi, Isaac; Sheiner, Eyal
2014-02-01
To evaluate pregnancy outcome and rates of anemia in patients following bariatric operation in comparison with obese pregnant women. A retrospective population-based study comparing pregnancy outcome of patients following bariatric with the obese population was conducted. Multivariate logistic regression models were constructed to control for confounders. To evaluate the change in hemoglobin levels, we included women who had one pregnancy before the bariatric surgery and one following the surgery or two pregnancies for women with obesity. This study included 326 women who had one pregnancy before and after a bariatric surgery and 1612 obese women who had at least two consecutive deliveries. Using a multivariable logistic regression model, controlling for confounders such as maternal age, patients following bariatric surgery had lower rates of gestational diabetes mellitus (OR 0.7; 95% CI 0.5-0.9; p = 0.49) and macrosomia (OR 0.3; 95% CI 0.2-0.5; p < 0.001) as compared with obese parturients. Women post bariatric surgery were more likely to be anemic (hemoglobin <10 g/dL) as compared to obese parturients (48% versus 37%; OR, 1.5; 95% CI, 1.2-1.9; p < 0.001). A significant decline in hemoglobin level was noted in patients following bariatric surgery (a decline of 0.33 g/dL versus 0.18 g/dL between two consecutive pregnancies of obese women). Using another multivariable model with anemia as the outcome variable, bariatric was noted as a risk factor for anemia (adjusted OR = 1.45, 95%CI 1.13-1.86, p = 0.004). Women following bariatric surgery have lower risk for gestational diabetes mellitus and fetal macrosomia as compared with obese parturients. Nevertheless, bariatric surgery is a risk factor for anemia.
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Brown, Anthony; Gibson, Richard; Tavener, Meredith; Guest, Maya; D'Este, Catherine; Byles, Julie; Attia, John; Horsley, Keith; Harrex, Warren; Ross, James
2009-06-01
In Australia, four formal F-111 fuel tank deseal/reseal (DSRS) repair programs were implemented over more than two decades, each involving different processes and using a range of hazardous substances. However, health concerns were raised by a number of workers. The "Study of Health Outcomes in Aircraft Maintenance Personnel" was commissioned by the Australian Department of Defence to investigate potential adverse health outcomes as a result of being involved in the deseal/reseal processes. To compare measures of sexual function in F-111 aircraft fuel tank DSRS maintenance workers, against two appropriate comparison groups. Exposed and comparison participants completed a postal questionnaire which included general questions of health and health behavior, and two specific questions on sexual functioning. They also completed the International Index of Erectile Function (IIEF) questionnaire. Logistic regression was used to explore exposure status and outcome while adjusting for potential confounders. The three outcomes of interest for this study were the proportion of participants with erectile dysfunction (ED) according to the IIEF, the proportion with self-reported loss of interest in sex, and the proportion with self-reported problems with sexual functioning. Compared with each of the comparison groups, a larger proportion of the exposed group reported sexual problems and were classified as having ED according to the IIEF. In logistic regression, the odds of all three outcomes were higher for exposed participants relative to each comparison group and after adjustment for potentially confounding variables including anxiety and depression. There was a consistent problem with sexual functioning in the exposed group that is not explained by anxiety and depression, and it appears related to DSRS activities.
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Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross
Ferris, Martin T.; Aylor, David L.; Bottomly, Daniel; Whitmore, Alan C.; Aicher, Lauri D.; Bell, Timothy A.; Bradel-Tretheway, Birgit; Bryan, Janine T.; Buus, Ryan J.; Gralinski, Lisa E.; Haagmans, Bart L.; McMillan, Leonard; Miller, Darla R.; Rosenzweig, Elizabeth; Valdar, William; Wang, Jeremy; Churchill, Gary A.; Threadgill, David W.; McWeeney, Shannon K.; Katze, Michael G.; Pardo-Manuel de Villena, Fernando; Baric, Ralph S.; Heise, Mark T.
2013-01-01
Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss. PMID:23468633
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NASA Astrophysics Data System (ADS)
Jacobsen, Robert E.; Burr, Devon M.
2018-03-01
Changes in Martian fluvial geomorphology with time-stratigraphic age, including decreases in paleochannel widths, suggest waning paleodischarges through time. Where fluvial landforms do not preserve paleochannel widths (e.g., meander deposits), other landform dimensions (i.e., radius of curvature) may be used to estimate paleodischarges. In the Aeolis Dorsa region, topographically inverted and stacked fluvial deposits - wide meander point bars overlain by thin channel fills - preserve ostensible evidence of decreasing paleodischarges through time. However, a robust paleohydraulic analysis of these distinct deposits requires knowledge of the accuracy of a terrestrial-based empirical relationship that estimates channel width from point-bar radius of curvature. We assess the accuracy of this radius-width relationship by applying it to a well-studied terrestrial analog, the Quinn River, Nevada. We find that radii of curvature from the Quinn River exceed the values predicted from the empirical relationship. These anomalously high radii are associated with greater resistance in the channel cut banks, indicating that bank strength is a confounding factor in the radius-width relationship. Some deposits in the Aeolis Dorsa include irregular meander morphologies, suggesting variably resistant channel banks and overestimates of both paleochannel widths and paleodischarges. Furthermore, the morphometry of the overlying thin channel fills suggests their widths have been eroded, such that their paleodischarges are underestimates. These overestimates and underestimates, when considered together, suggest little change in paleodischarge during the stratigraphic transition from meander deposits to channel fills. This work demonstrates the importance of terrestrial analog studies for revealing confounding factors in Martian fluvial systems and cautions against simplistic interpretations of Martian fluvial history. The discovered inaccuracies of paleodischarge estimates expose sources of uncertainty in the extant paleodischarge data that bias inferences toward waning hydrologic activity through time.
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2010-03-20
olive oil (placebo) capsules (treatment 2). Potential confounding variables are assessed through completion of a comprehensive diet history...AD_________________ Award Number: W81XWH-04-1-0296 TITLE: Fish Oil Supplementation and Fatty Acid...FORM TO THE ABOVE ADDRESS. 31-03-2010 1. REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 0 3. DATES COVERED (From - To) Fish Oil Supplementation and
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Equal Pay for Equal Work in Academic Obstetrics and Gynecology.
Eichelberger, Kacey Y
2018-02-01
The most compelling data suggest women in academic obstetrics and gynecology earn approximately $36,000 less than male colleagues per year in regression models correcting for commonly cited explanatory variables. Although residual confounding may exist, academic departments in the United States should consider rigorous examination of their own internal metrics around salary to ensure gender-neutral compensation, commonly referred to as equal pay for equal work.
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Hayashi, Tatsuya; Saitoh, Satoshi; Takahashi, Junji; Tsuji, Yoshinori; Ikeda, Kenji; Kobayashi, Masahiro; Kawamura, Yusuke; Fujii, Takeshi; Inoue, Masafumi; Miyati, Tosiaki; Kumada, Hiromitsu
2017-04-01
The two-point Dixon method for magnetic resonance imaging (MRI) is commonly used to non-invasively measure fat deposition in the liver. The aim of the present study was to assess the usefulness of MRI-fat fraction (MRI-FF) using the two-point Dixon method based on the non-alcoholic fatty liver disease activity score. This retrospective study included 106 patients who underwent liver MRI and MR spectroscopy, and 201 patients who underwent liver MRI and histological assessment. The relationship between MRI-FF and MR spectroscopy-fat fraction was used to estimate the corrected MRI-FF for hepatic multi-peaks of fat. Then, a color FF map was generated with the corrected MRI-FF based on the non-alcoholic fatty liver disease activity score. We defined FF variability as the standard deviation of FF in regions of interest. Uniformity of hepatic fat was visually graded on a three-point scale using both gray-scale and color FF maps. Confounding effects of histology (iron, inflammation and fibrosis) on corrected MRI-FF were assessed by multiple linear regression. The linear correlations between MRI-FF and MR spectroscopy-fat fraction, and between corrected MRI-FF and histological steatosis were strong (R 2 = 0.90 and R 2 = 0.88, respectively). Liver fat variability significantly increased with visual fat uniformity grade using both of the maps (ρ = 0.67-0.69, both P < 0.001). Hepatic iron, inflammation and fibrosis had no significant confounding effects on the corrected MRI-FF (all P > 0.05). The two-point Dixon method and the gray-scale or color FF maps based on the non-alcoholic fatty liver disease activity score were useful for fat quantification in the liver of patients without severe iron deposition. © 2016 The Japan Society of Hepatology.
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The Association of Visual Impairment With Clinical Outcomes in Hemodialysis Patients
Hong, Yu Ah; Kim, Suk Young; Kim, Su-Hyun; Kim, Young Ok; Jin, Dong Chan; Song, Ho Chul; Choi, Euy Jin; Kim, Yong-Lim; Kim, Yon-Su; Kang, Shin-Wook; Kim, Nam-Ho; Yang, Chul Woo; Kim, Yong Kyun
2016-01-01
Abstract Visual impairment limits people's ability to perform daily tasks and affects their quality of life. We evaluated the impact of visual impairment on clinical outcomes in hemodialysis (HD) patients. HD patients were selected from the Clinical Research Center registry a prospective cohort study on dialysis patients in Korea. Visual impairment was defined as difficulty in daily life due to decreased visual acuity or blindness. The primary outcome was all-cause mortality and the secondary outcomes were cardiovascular and infection-related hospitalization. A total of 3250 patients were included. Seven hundred thirty (22.5%) of the enrolled patients had visual impairment. The median follow-up period was 30 months. The Kaplan–Meier curve and log-rank test showed that all-cause mortality rates (P < 0.001) as well as cardiovascular and infection-related hospitalization rates (P < 0.001 and P < 0.001) were significantly higher in patients with visual impairment than in patients without visual impairment. In the multivariable analysis, visual impairment had significant predictive power for all-cause mortality (Hazard ratio [HR], 1.77, 95% confidence interval [CI], 1.21–2.61, P = 0.004) and cardiovascular hospitalization (HR 1.45 [1.00–1.90], P = 0.008) after adjusting for confounding variables. Of these 3250 patients, 634 patients from each group were matched by propensity scores. In the propensity score matched analysis, patients with visual impairment had independently significant associations with increased all-cause mortality (HR 1.69 [1.12–2.54], P = 0.01) and cardiovascular hospitalization (HR 1.48 [1.08–2.02], P = 0.01) compared with patients without visual impairment after adjustment for confounding variables. Our data demonstrated that visual impairment was an independent risk factor for clinical adverse outcomes in HD patients. PMID:27175661
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Shaul, Chanan; Blotnick, Simcha; Muszkat, Mordechai; Bialer, Meir; Caraco, Yoseph
2017-02-01
Genetic polymorphisms in CYP2C9 account for 10-20% of the variability in warfarin dose requirement. As such CYP2C9 genetic polymorphisms are commonly included in algorithms aimed to optimize warfarin therapy as a way to account for variability in warfarin responsiveness that is due to altered pharmacokinetics. However, most of the currently available pharmacokinetic data were derived from studies among patients on chronic warfarin therapy and therefore suffer from the confounding effects of disease states and drug interactions. The purpose of the present study was to provide an accurate quantitative estimate of S-warfarin oral clearance (CL S ) among healthy subjects carrying different CYP2C9 genotypes. Single dose of warfarin was administered to 150 non-smokers, age (mean ± SD) 23.3 ± 4.5 years, 60% male, non-obese, healthy subjects. Blood samples were taken for up to 168 h and urine was collected over the entire study period. Compared with carriers of the wild-type CYP2C9*1/*1 genotype (n = 69), CL S was reduced by 25, 39 and 47% among heterozygote for CYP2C9*2 (n = 41) CYP2C9*3 (n = 26) and carriers of 2 variant alleles (n = 14), respectively (p < 0.001). The corresponding decrease in the formation clearance of 6 and 7 S-hydroxy-warfarin was 45, 65 and 75%, respectively (p < 0.001). The current study provides an estimate concerning the effect of CYP2C9 polymorphisms on S-warfarin pharmacokinetics among healthy subjects. As such it is free of the confounding effects of disease states and drug interactions. Further research is needed to evaluate whether the incorporation of quantitative data obtained in the present study into pharmacogenetic warfarin algorithm may enhance its precision. Clinicaltrials.gov Identifier NCT00162474.
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Cox, Louis Anthony Tony
2017-05-01
Asthma in the United States has become an important public health issue, with many physicians, regulators, and scientists elsewhere expressing concern that criterion air pollutants have contributed to a rising tide of asthma cases and symptoms. This paper studies recent associations (from 2008 to 2012) between self-reported asthma experiences and potential predictors, including age, sex, income, education, smoking, and county-level average annual ambient concentrations of ozone (O3) and fine particulate matter (PM2.5) levels recorded by the U.S. Environmental Protection Agency, for adults 50 years old or older for whom survey data are available from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS). We also examine associations between these variables and self-reported heart attack and stroke experience; all three health outcomes are positively associated with each other. Young divorced women with low incomes are at greatest risk of asthma, especially if they are ever-smokers. Income is an important confounder of other relations. For example, in logistic regression modeling, PM2.5 is positively associated (p<0.06) with both stroke risk and heart attack risk when these are regressed only against PM2.5, sex, age, and ever-smoking status, but not when they are regressed against these variables and income. In this data set, PM2.5 is significantly negatively associated with asthma risk in regression models, with a 10μg/m 3 decrease in PM2.5 corresponding to about a 6% increase in the probability of asthma, possibly because of confounding by smoking, which is negatively associated with PM2.5 and positively associated with asthma risk. A variety of non-parametric methods are used to quantify these associations and to explore potential causal interpretations. Copyright © 2017. Published by Elsevier Inc.
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Lead exposure potentiates predatory attack behavior in the cat.
Li, Wenjie; Han, Shenggao; Gregg, Thomas R; Kemp, Francis W; Davidow, Amy L; Louria, Donald B; Siegel, Allan; Bogden, John D
2003-07-01
Epidemiologic studies have demonstrated that environmental lead exposure is associated with aggressive behavior in children; however, numerous confounding variables limit the ability of these studies to establish a causal relationship. The study of aggressive behavior using a validated animal model was used to test the hypothesis that there is a causal relationship between lead exposure and aggression in the absence of confounding variables. We studied the effects of lead exposure on a feline model of aggression: predatory (quiet biting) attack of an anesthetized rat. Five cats were stimulated with a precisely controlled electrical current via electrodes inserted into the lateral hypothalamus. The response measure was the predatory attack threshold current (i.e., the current required to elicit an attack response on 50% of the trials). Blocks of trials were administered in which predatory attack threshold currents were measured three times a week for a total of 6-10 weeks, including before, during, and after lead exposure. Lead was incorporated into cat food "treats" at doses of 50-150 mg/kg/day. Two of the five cats received a second period of lead exposure. Blood lead concentrations were measured twice a week and were <1, 21-77, and <20 micro g/dL prior to, during, and after lead exposure, respectively. The predatory attack threshold decreased significantly during initial lead exposure in three of five cats and increased after the cessation of lead exposure in four of the five cats (P<0.01). The predatory attack thresholds and blood lead concentrations for each cat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed model demonstrated a significant (P=0.0019) negative association between threshold current and blood lead concentration. The data of this study demonstrate that lead exposure enhances predatory aggression in the cat and provide experimental support for a causal relationship between lead exposure and aggressive behavior in humans.
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Jucker, Jean-Luc; Thornborrow, Tracey; Beierholm, Ulrik; Burt, D Michael; Barton, Robert A; Evans, Elizabeth H; Jamieson, Mark A; Tovée, Martin J; Boothroyd, Lynda G
2017-08-16
Television consumption influences perceptions of attractive female body size. However, cross-cultural research examining media influence on body ideals is typically confounded by differences in the availability of reliable and diverse foodstuffs. 112 participants were recruited from 3 Nicaraguan villages that differed in television consumption and nutritional status, such that the contribution of both factors could be revealed. Participants completed a female figure preference task, reported their television consumption, and responded to several measures assessing nutritional status. Communities with higher television consumption and/or higher nutritional status preferred thinner female bodies than communities with lower television consumption and/or lower nutritional status. Bayesian mixed models estimated the plausible range of effects for television consumption, nutritional status, and other relevant variables on individual preferences. The model explained all meaningful differences between our low-nutrition villages, and television consumption, after sex, was the most likely of these predictors to contribute to variation in preferences (probability mass >95% when modelling only variables with zero-order associations with preferences, but only 90% when modelling all possible predictors). In contrast, we found no likely link with nutritional status. We thus found evidence that where media access and nutritional status are confounded, media is the more likely predictor of body ideals.
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Errors in causal inference: an organizational schema for systematic error and random error.
Suzuki, Etsuji; Tsuda, Toshihide; Mitsuhashi, Toshiharu; Mansournia, Mohammad Ali; Yamamoto, Eiji
2016-11-01
To provide an organizational schema for systematic error and random error in estimating causal measures, aimed at clarifying the concept of errors from the perspective of causal inference. We propose to divide systematic error into structural error and analytic error. With regard to random error, our schema shows its four major sources: nondeterministic counterfactuals, sampling variability, a mechanism that generates exposure events and measurement variability. Structural error is defined from the perspective of counterfactual reasoning and divided into nonexchangeability bias (which comprises confounding bias and selection bias) and measurement bias. Directed acyclic graphs are useful to illustrate this kind of error. Nonexchangeability bias implies a lack of "exchangeability" between the selected exposed and unexposed groups. A lack of exchangeability is not a primary concern of measurement bias, justifying its separation from confounding bias and selection bias. Many forms of analytic errors result from the small-sample properties of the estimator used and vanish asymptotically. Analytic error also results from wrong (misspecified) statistical models and inappropriate statistical methods. Our organizational schema is helpful for understanding the relationship between systematic error and random error from a previously less investigated aspect, enabling us to better understand the relationship between accuracy, validity, and precision. Copyright © 2016 Elsevier Inc. All rights reserved.
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Effect of Breastfeeding on Head Circumference of Children from Impoverished Communities
Xavier Júnior, Antonio Fernando Silva; de Assunção, Monica Lopes; dos Santos, Ewerton Amorim; Horta, Bernardo Lessa
2013-01-01
Abstract Objective This study investigated the effect of exclusive breastfeeding on head circumference (HC) among children living in impoverished communities. Subjects and Methods A cross-sectional study was conducted among children 12–60 months old from the 39 quilombos located in the State of Alagoas, Brazil. HC deficit was defined by a z-score of less than −2 from the median (based on the 2006 World Health Organization growth standards). Prevalence ratio and 95% confidence interval (95% CI) were estimated using Poisson regression with robust adjustment of the variance, and estimates were adjusted for possible confounders (anthropometric, socioeconomic, demographic, and health-related variables). Results We evaluated 725 children (365 boys and 360 girls). The prevalence of HC deficit was 13.3% among those children who were exclusively breastfed for less than 30 days, 10.6% among those exclusively breastfed for 30–119 days, and 5.8% among those who were exclusively breastfed for 120 days or more. Even after controlling for possible confounding variables, exclusive breastfeeding for ≥4 months decreased the risk of HC deficit (prevalence ratio, 0.48; 95% CI 0.24, 0.99). Conclusions Exclusive breastfeeding for ≥4 months was associated with a larger HC in children exposed to great social vulnerability in impoverished communities. PMID:23414229
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, T.N.; Ko, Y.C.; Chao, Y.Y.
The study aim was to estimate the contribution of indoor and outdoor air pollution to the 1-year prevalence of adolescent asthma after personal susceptibility and other potential risk factors were taken into account. A large-scaled cross-sectional study was conducted among 165,173 high school students aged 11 to 16 years in the different communities of Kaohsiung and Pintong in Taiwan, from October 1995 to June 1996. Each student and his/her parents participating in the study completed a video and a written International Study of Asthma and Allergies in Childhood questionnaire about symptoms of wheezing and allergies, passive smoking, and demographic variables.more » After adjustment for potential confounders, adolescents exposed to cigarette smoking and environmental tobacco smoke were found to suffer from asthma at an increased frequency. The authors observed a statistically significant association between outdoor air pollution and asthma, after controlling for potential confound variables. Total suspended particulate, nitrogen dioxide, carbon monoxide, ozone, and airborne dust particles all displayed an independent association with asthma, respectively. There were no selection biases in this community-based study, which provides evidence that passive smoking and long-term, high average outdoor air pollution are independent risk factors of asthma.« less
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Hassenrück, Christiane; Fink, Artur; Lichtschlag, Anna; Tegetmeyer, Halina E; de Beer, Dirk; Ramette, Alban
2016-05-01
To understand how ocean acidification (OA) influences sediment microbial communities, naturally CO2-rich sites are increasingly being used as OA analogues. However, the characterization of these naturally CO2-rich sites is often limited to OA-related variables, neglecting additional environmental variables that may confound OA effects. Here, we used an extensive array of sediment and bottom water parameters to evaluate pH effects on sediment microbial communities at hydrothermal CO2 seeps in Papua New Guinea. The geochemical composition of the sediment pore water showed variations in the hydrothermal signature at seep sites with comparable pH, allowing the identification of sites that may better represent future OA scenarios. At these sites, we detected a 60% shift in the microbial community composition compared with reference sites, mostly related to increases in Chloroflexi sequences. pH was among the factors significantly, yet not mainly, explaining changes in microbial community composition. pH variation may therefore often not be the primary cause of microbial changes when sampling is done along complex environmental gradients. Thus, we recommend an ecosystem approach when assessing OA effects on sediment microbial communities under natural conditions. This will enable a more reliable quantification of OA effects via a reduction of potential confounding effects. © FEMS 2016.
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Biddle, Jennifer C; Koontz, Tomas M
2014-12-01
Collaborative governance critics continually call for evidence to support its prevalent use. As is often the case in environmental policy, environmental outcomes occur at a rate incompatible with political agendas. In addition, a multitude of possibly confounding variables makes it difficult to correlate collaborative governance processes with environmental outcomes. The findings of this study offer empirical evidence that collaborative processes have a measurable, beneficial effect on environmental outcomes. Through the use of a unique paired-waterbody design, our dataset reduced the potential for confounding variables to impact our environmental outcome measurements. The results of a path analysis indicate that the output of setting specific pollutant reduction goals is significantly related to watershed partnerships' level of attainment of their environmental improvement goals. The action of setting specific goals (e.g. percentage of load reductions in pollutant levels) is fostered by sustained participation from partnership members throughout the lifecycle of the collaborative. In addition, this study demonstrates the utility of logic modeling for environmental planning and management, and suggests that the process of setting specific pollutant reduction goals is a useful proxy measure for reporting progress towards improvements in environmental outcomes when long-term environmental data are not available. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Measurement error is often neglected in medical literature: a systematic review.
Brakenhoff, Timo B; Mitroiu, Marian; Keogh, Ruth H; Moons, Karel G M; Groenwold, Rolf H H; van Smeden, Maarten
2018-06-01
In medical research, covariates (e.g., exposure and confounder variables) are often measured with error. While it is well accepted that this introduces bias and imprecision in exposure-outcome relations, it is unclear to what extent such issues are currently considered in research practice. The objective was to study common practices regarding covariate measurement error via a systematic review of general medicine and epidemiology literature. Original research published in 2016 in 12 high impact journals was full-text searched for phrases relating to measurement error. Reporting of measurement error and methods to investigate or correct for it were quantified and characterized. Two hundred and forty-seven (44%) of the 565 original research publications reported on the presence of measurement error. 83% of these 247 did so with respect to the exposure and/or confounder variables. Only 18 publications (7% of 247) used methods to investigate or correct for measurement error. Consequently, it is difficult for readers to judge the robustness of presented results to the existence of measurement error in the majority of publications in high impact journals. Our systematic review highlights the need for increased awareness about the possible impact of covariate measurement error. Additionally, guidance on the use of measurement error correction methods is necessary. Copyright © 2018 Elsevier Inc. All rights reserved.
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Viral Diseases in Zebrafish: What Is Known and Unknown
Crim, Marcus J.; Riley, Lela K.
2013-01-01
Naturally occurring viral infections have the potential to introduce confounding variability that leads to invalid and misinterpreted data. Whereas the viral diseases of research rodents are well characterized and closely monitored, no naturally occurring viral infections have been characterized for the laboratory zebrafish (Danio rerio), an increasingly important biomedical research model. Despite the ignorance about naturally occurring zebrafish viruses, zebrafish models are rapidly expanding in areas of biomedical research where the confounding effects of unknown infectious agents present a serious concern. In addition, many zebrafish research colonies remain linked to the ornamental (pet) zebrafish trade, which can contribute to the introduction of new pathogens into research colonies, whereas mice used for research are purpose bred, with no introduction of new mice from the pet industry. Identification, characterization, and monitoring of naturally occurring viruses in zebrafish are crucial to the improvement of zebrafish health, the reduction of unwanted variability, and the continued development of the zebrafish as a model organism. This article addresses the importance of identifying and characterizing the viral diseases of zebrafish as the scope of zebrafish models expands into new research areas and also briefly addresses zebrafish susceptibility to experimental viral infection and the utility of the zebrafish as an infection and immunology model. PMID:23382345
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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
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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.
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Mascha, Edward J; Dalton, Jarrod E; Kurz, Andrea; Saager, Leif
2013-10-01
In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.
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Lima, Aurea; Monteiro, Joaquim; Bernardes, Miguel; Sousa, Hugo; Azevedo, Rita; Seabra, Vitor; Medeiros, Rui
2014-01-01
Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; P = 0.013) and ATIC 675T carriers (OR = 5.16; P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; P = 0.004) and antinuclear antibodies (OR = 2.28; P = 0.045), with higher health assessment questionnaire score (OR = 2.42; P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77; P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; P < 0.001) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. PMID:24967362
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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.
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Three estimates of the association between linear growth failure and cognitive ability.
Cheung, Y B; Lam, K F
2009-09-01
To compare three estimators of association between growth stunting as measured by height-for-age Z-score and cognitive ability in children, and to examine the extent statistical adjustment for covariates is useful for removing confounding due to socio-economic status. Three estimators, namely random-effects, within- and between-cluster estimators, for panel data were used to estimate the association in a survey of 1105 pairs of siblings who were assessed for anthropometry and cognition. Furthermore, a 'combined' model was formulated to simultaneously provide the within- and between-cluster estimates. Random-effects and between-cluster estimators showed strong association between linear growth and cognitive ability, even after adjustment for a range of socio-economic variables. In contrast, the within-cluster estimator showed a much more modest association: For every increase of one Z-score in linear growth, cognitive ability increased by about 0.08 standard deviation (P < 0.001). The combined model verified that the between-cluster estimate was significantly larger than the within-cluster estimate (P = 0.004). Residual confounding by socio-economic situations may explain a substantial proportion of the observed association between linear growth and cognition in studies that attempt to control the confounding by means of multivariable regression analysis. The within-cluster estimator provides more convincing and modest results about the strength of association.
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Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R
2016-12-01
In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.
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Sauchyn, David J.; St-Jacques, Jeannine-Marie; Luckman, Brian H.
2015-01-01
Exploitation of the Alberta oil sands, the world’s third-largest crude oil reserve, requires fresh water from the Athabasca River, an allocation of 4.4% of the mean annual flow. This allocation takes into account seasonal fluctuations but not long-term climatic variability and change. This paper examines the decadal-scale variability in river discharge in the Athabasca River Basin (ARB) with (i) a generalized least-squares (GLS) regression analysis of the trend and variability in gauged flow and (ii) a 900-y tree-ring reconstruction of the water-year flow of the Athabasca River at Athabasca, Alberta. The GLS analysis removes confounding transient trends related to the Pacific Decadal Oscillation (PDO) and Pacific North American mode (PNA). It shows long-term declining flows throughout the ARB. The tree-ring record reveals a larger range of flows and severity of hydrologic deficits than those captured by the instrumental records that are the basis for surface water allocation. It includes periods of sustained low flow of multiple decades in duration, suggesting the influence of the PDO and PNA teleconnections. These results together demonstrate that low-frequency variability must be considered in ARB water allocation, which has not been the case. We show that the current and projected surface water allocations from the Athabasca River for the exploitation of the Alberta oil sands are based on an untenable assumption of the representativeness of the short instrumental record. PMID:26392554
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Sex Differences in Response to Visual Sexual Stimuli: A Review
Rupp, Heather A.; Wallen, Kim
2009-01-01
This article reviews what is currently known about how men and women respond to the presentation of visual sexual stimuli. While the assumption that men respond more to visual sexual stimuli is generally empirically supported, previous reports of sex differences are confounded by the variable content of the stimuli presented and measurement techniques. We propose that the cognitive processing stage of responding to sexual stimuli is the first stage in which sex differences occur. The divergence between men and women is proposed to occur at this time, reflected in differences in neural activation, and contribute to previously reported sex differences in downstream peripheral physiological responses and subjective reports of sexual arousal. Additionally, this review discusses factors that may contribute to the variability in sex differences observed in response to visual sexual stimuli. Factors include participant variables, such as hormonal state and socialized sexual attitudes, as well as variables specific to the content presented in the stimuli. Based on the literature reviewed, we conclude that content characteristics may differentially produce higher levels of sexual arousal in men and women. Specifically, men appear more influenced by the sex of the actors depicted in the stimuli while women’s response may differ with the context presented. Sexual motivation, perceived gender role expectations, and sexual attitudes are possible influences. These differences are of practical importance to future research on sexual arousal that aims to use experimental stimuli comparably appealing to men and women and also for general understanding of cognitive sex differences. PMID:17668311
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Akachi, Yoko; Zumla, Alimuddin; Atun, Rifat
2012-05-15
To assess the impact of investment in national tuberculosis programs (NTPs) on NTP performance and tuberculosis burden in 22 high-burden countries, as determined by the World Health Organization (WHO). Estimates of annual tuberculosis burden and NTP performance indicators and control variables during 2002-2009 were obtained from the Organization for Economic Cooperation and Development, the WHO, the World Bank, and the Penn World Table for the 22 high-burden countries. Panel data analysis was performed using the outcome variables tuberculosis incidence, prevalence, and mortality and the key explanatory variables Partnership case detection rate and treatment success rate, controlling for gross domestic product per capita, population structure, and human immunodeficiency virus (HIV) prevalence. A $1 per capita (general population) higher NTP budget (including domestic and external sources) was associated with a 1.9% (95% confidence interval, .12%-3.6%) higher estimated case detection rate the following year for the 22 high-burden countries between 2002 and 2009. In the final models, which corrected for autocorrelation and heteroskedasticity, achieving the STOP TB Partnership case detection rate target of >70% was associated with significantly (P < .01) lower tuberculosis incidence, prevalence, and mortality the following year, even when controlling for general economic development and HIV prevalence as potential confounding variables. Increased investment in NTPs was significantly associated with improved performance and with a downward trend in the tuberculosis burden in the 22 high-burden countries during 2002-2009.
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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.
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Henderson, Virginia P; Massion, Ann O; Clemow, Lynn; Hurley, Thomas G; Druker, Susan; Hébert, James R
2013-09-01
To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA)undergoing radiotherapy. Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables. A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control. MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.
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Predictors of participation in sports after hip and knee arthroplasty.
Williams, Daniel H; Greidanus, Nelson V; Masri, Bassam A; Duncan, Clive P; Garbuz, Donald S
2012-02-01
While the primary objective of joint arthroplasty is to improve patient quality of life, pain, and function, younger active patients often demand a return to higher function that includes sporting activity. Knowledge of rates and predictors of return to sports will help inform expectations in patients anticipating return to sports after joint arthroplasty. We measured the rate of sports participation at 1 year using the UCLA activity score and explored 11 variables, including choice of procedure/prosthesis, that might predict return to a high level of sporting activity, when controlling for potential confounding variables. We retrospectively evaluated 736 patients who underwent primary metal-on-polyethylene THA, metal-on-metal THA, hip resurfacing arthroplasty, revision THA, primary TKA, unicompartmental knee arthroplasty, and revision TKA between May 2005 and June 2007. We obtained UCLA activity scores on all patients; we defined high activity as a UCLA score of 7 or more. We evaluated patient demographics (age, sex, BMI, comorbidity), quality of life (WOMAC score, Oxford Hip Score, SF-12 score), and surgeon- and procedural/implant-specific variables to identify factors associated with postoperative activity score. Minimum followup was 11 months (mean, 12.1 months; range, 11-13 months). Preoperative UCLA activity score, age, male sex, and BMI predicted high activity scores. The type of operation and implant characteristics did not predict return to high activity sports. Our data suggest patient-specific factors predict postoperative activity rather than factors specific to type of surgery, implant, or surgeon factors. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
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Poverty, Pregnancy, and Birth Outcomes: A Study of the Earned Income Tax Credit
Rehkopf, David H.
2015-01-01
Background Economic interventions are increasingly recognized as a mechanism to address perinatal health outcomes among disadvantaged groups. In the United States, the earned income tax credit (EITC) is the largest poverty alleviation program. Little is known about its effects on perinatal health among recipients and their children. We exploit quasi-random variation in the size of EITC payments over time to examine the effects of income on perinatal health. Methods The study sample includes women surveyed in the 1979 National Longitudinal Survey of Youth (N=2,985) and their children born during 1986–2000 (N=4,683). Outcome variables include utilization of prenatal and postnatal care, use of alcohol and tobacco during pregnancy, term birth, birthweight, and breast-feeding status. We examine the health effects of both household income and EITC payment size using multivariable linear regressions. We employ instrumental variables analysis to estimate the causal effect of income on perinatal health, using EITC payment size as an instrument for household income. Results We find that household income and EITC payment size are associated with improvements in several indicators of perinatal health. Instrumental variables analysis, however, does not reveal a causal association between household income and these health measures. Conclusions Our findings suggest that associations between income and perinatal health may be confounded by unobserved characteristics, but that EITC income improves perinatal health. Future studies should continue to explore the impacts of economic interventions on perinatal health outcomes, and investigate how different forms of income transfers may have different impacts. PMID:26212041