When can the cause of a population decline be determined?

USGS Publications Warehouse

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

2016-01-01

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

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

PubMed Central

2013-01-01

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

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

PubMed

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

2018-05-21

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

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

PubMed

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

2012-12-01

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

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

PubMed Central

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

2013-01-01

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

Bayesian effect estimation accounting for adjustment uncertainty.

PubMed

Wang, Chi; Parmigiani, Giovanni; Dominici, Francesca

2012-09-01

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

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

PubMed

Vetter, Thomas R; Mascha, Edward J

2017-09-01

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

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

PubMed

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

2013-08-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2013-07-01

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

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

PubMed

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

2017-01-01

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

Occupational exposure and ovarian cancer risk.

PubMed

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

2014-07-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2017-01-01

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

Accounting for context in studies of health inequalities: a review and comparison of analytic approaches.

PubMed

Schempf, Ashley H; Kaufman, Jay S

2012-10-01

A common epidemiologic objective is to evaluate the contribution of residential context to individual-level disparities by race or socioeconomic position. We reviewed analytic strategies to account for the total (observed and unobserved factors) contribution of environmental context to health inequalities, including conventional fixed effects (FE) and hybrid FE implemented within a random effects (RE) or a marginal model. To illustrate results and limitations of the various analytic approaches of accounting for the total contextual component of health disparities, we used data on births nested within neighborhoods as an applied example of evaluating neighborhood confounding of racial disparities in gestational age at birth, including both a continuous and a binary outcome. Ordinary and RE models provided disparity estimates that can be substantially biased in the presence of neighborhood confounding. Both FE and hybrid FE models can account for cluster level confounding and provide disparity estimates unconfounded by neighborhood, with the latter having greater flexibility in allowing estimation of neighborhood-level effects and intercept/slope variability when implemented in a RE specification. Given the range of models that can be implemented in a hybrid approach and the frequent goal of accounting for contextual confounding, this approach should be used more often. Published by Elsevier Inc.

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

PubMed

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

2015-01-01

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

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

PubMed

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

2015-03-01

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

Permethrin Exposure Dosimetry: Biomarkers and Modifiable Factors

DTIC Science & Technology

2017-08-01

metabolite; (F = 16.16, p < 0.0001). This association holds after controlling for known confounders including sex , age, time that uniform was worn...and metabolite concentrations were examined via linear mixed modeling. All models were adjusted for creatinine, age, sex , days in BCT, number of

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

PubMed

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

2009-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci

PubMed Central

Ju, Jin Hyun; Crystal, Ronald G.

2017-01-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL. PMID:28505156

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

PubMed

Ju, Jin Hyun; Shenoy, Sushila A; Crystal, Ronald G; Mezey, Jason G

2017-05-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL.

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

PubMed

Loeys, Tom; Josephy, Haeike; Dewitte, Marieke

2018-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

USDA-ARS?s Scientific Manuscript database

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

Developing hazelnut tissue culture medium free of ion confounding

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

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

2011-03-01

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

Birth weight and mortality: causality or confounding?

PubMed

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

2006-08-15

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

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

PubMed

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

2016-05-01

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

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

PubMed

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

2016-04-01

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

Human Health and Exposure to Electromagnetic Radiation

DTIC Science & Technology

1992-07-01

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

2008-02-01

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

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

PubMed

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

2013-08-01

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

Trimodel Mammography with Perfect Coregistration

DTIC Science & Technology

2017-02-01

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

Epidemiologic methods in clinical trials.

PubMed

Rothman, K J

1977-04-01

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

Conditional Random Fields for Fast, Large-Scale Genome-Wide Association Studies

PubMed Central

Huang, Jim C.; Meek, Christopher; Kadie, Carl; Heckerman, David

2011-01-01

Understanding the role of genetic variation in human diseases remains an important problem to be solved in genomics. An important component of such variation consist of variations at single sites in DNA, or single nucleotide polymorphisms (SNPs). Typically, the problem of associating particular SNPs to phenotypes has been confounded by hidden factors such as the presence of population structure, family structure or cryptic relatedness in the sample of individuals being analyzed. Such confounding factors lead to a large number of spurious associations and missed associations. Various statistical methods have been proposed to account for such confounding factors such as linear mixed-effect models (LMMs) or methods that adjust data based on a principal components analysis (PCA), but these methods either suffer from low power or cease to be tractable for larger numbers of individuals in the sample. Here we present a statistical model for conducting genome-wide association studies (GWAS) that accounts for such confounding factors. Our method scales in runtime quadratic in the number of individuals being studied with only a modest loss in statistical power as compared to LMM-based and PCA-based methods when testing on synthetic data that was generated from a generalized LMM. Applying our method to both real and synthetic human genotype/phenotype data, we demonstrate the ability of our model to correct for confounding factors while requiring significantly less runtime relative to LMMs. We have implemented methods for fitting these models, which are available at http://www.microsoft.com/science. PMID:21765897

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

PubMed

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

2018-03-01

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

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

PubMed

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

2006-01-01

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

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

PubMed

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

2009-07-01

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

Sensory imbalance as mechanism of orientation disruption in the leafminer, Phyllocnistis citrella: Elucidation by multivariate geometric designs and response surface models

USDA-ARS?s Scientific Manuscript database

Experimental designs developed to address mixtures are ideally suited for many areas of experimental biology including pheromone blend studies because they address the confounding of proportionality and concentration intrinsic to factorial and one-factor-at-a-time designs. Geometric multivariate des...

A Systematic Review of Risk Factors for Intimate Partner Violence

PubMed Central

Capaldi, Deborah M.; Knoble, Naomi B.; Shortt, Joann Wu; Kim, Hyoun K.

2012-01-01

A systematic review of risk factors for intimate partner violence was conducted. Inclusion criteria included publication in a peer-reviewed journal, a representative community sample or a clinical sample with a control-group comparison, a response rate of at least 50%, use of a physical or sexual violence outcome measure, and control of confounding factors in the analyses. A total of 228 articles were included (170 articles with adult and 58 with adolescent samples). Organized by levels of a dynamic developmental systems perspective, risk factors included: (a) contextual characteristics of partners (demographic, neighborhood, community and school factors), (b) developmental characteristics and behaviors of the partners (e.g., family, peer, psychological/behavioral, and cognitive factors), and (c) relationship influences and interactional patterns. Comparisons to a prior review highlight developments in the field in the past 10 years. Recommendations for intervention and policy along with future directions for intimate partner violence (IPV) risk factor research are presented. PMID:22754606

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

PubMed

Morabia, A

1995-01-01

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

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

PubMed Central

Duncan, Niall W.; Northoff, Georg

2013-01-01

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

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

PubMed

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

2017-09-01

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

Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

PubMed

Anderson, D

2001-09-01

It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which affect them is complex. Sometimes the variables are not completely independent of each other.

The association between air pollution and type 2 diabetes in a large cross-sectional study in Leicester: The CHAMPIONS Study.

PubMed

O'Donovan, Gary; Chudasama, Yogini; Grocock, Samuel; Leigh, Roland; Dalton, Alice M; Gray, Laura J; Yates, Thomas; Edwardson, Charlotte; Hill, Sian; Henson, Joe; Webb, David; Khunti, Kamlesh; Davies, Melanie J; Jones, Andrew P; Bodicoat, Danielle H; Wells, Alan

2017-07-01

Observational evidence suggests there is an association between air pollution and type 2 diabetes; however, there is high risk of bias. To investigate the association between air pollution and type 2 diabetes, while reducing bias due to exposure assessment, outcome assessment, and confounder assessment. Data were collected from 10,443 participants in three diabetes screening studies in Leicestershire, UK. Exposure assessment included standard, prevailing estimates of outdoor nitrogen dioxide and particulate matter concentrations in a 1×1km area at the participant's home postcode. Three-year exposure was investigated in the primary analysis and one-year exposure in a sensitivity analysis. Outcome assessment included the oral glucose tolerance test for type 2 diabetes. Confounder assessment included demographic factors (age, sex, ethnicity, smoking, area social deprivation, urban or rural location), lifestyle factors (body mass index and physical activity), and neighbourhood green space. Nitrogen dioxide and particulate matter concentrations were associated with type 2 diabetes in unadjusted models. There was no statistically significant association between nitrogen dioxide concentration and type 2 diabetes after adjustment for demographic factors (odds: 1.08; 95% CI: 0.91, 1.29). The odds of type 2 diabetes was 1.10 (95% CI: 0.92, 1.32) after further adjustment for lifestyle factors and 0.91 (95% CI: 0.72, 1.16) after yet further adjustment for neighbourhood green space. The associations between particulate matter concentrations and type 2 diabetes were also explained away by demographic factors. There was no evidence of exposure definition bias. Demographic factors seemed to explain the association between air pollution and type 2 diabetes in this cross-sectional study. High-quality longitudinal studies are needed to improve our understanding of the association. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2008-09-01

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

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

PubMed

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

2015-09-01

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

Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

PubMed

Tuk, Bert

2016-01-01

Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g ., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone-regardless of whether they present with syphilitic ALS or non-syphilitic ALS-may be effective at treating this rapidly progressive, highly devastating disease.

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

PubMed Central

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

2015-01-01

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

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

ERIC Educational Resources Information Center

Isacoff, Nora M.; Stromswold, Karin

2014-01-01

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

Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Paolisso, Giuseppe; Ble, Alessandro; Egan, Josephine M.; Metter, E. Jeffrey; Abbatecola, Angela M.; Zuliani, Giovanni; Ruggiero, Carmelinda; Valenti, Giorgio; Guralnik, Jack M.; Ferrucci, Luigi

2009-01-01

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (≥65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21–0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS. PMID:16968811

Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study.

PubMed

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Paolisso, Giuseppe; Ble, Alessandro; Egan, Josephine M; Metter, E Jeffrey; Abbatecola, Angela M; Zuliani, Giovanni; Ruggiero, Carmelinda; Valenti, Giorgio; Guralnik, Jack M; Ferrucci, Luigi

2007-01-01

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.

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

PubMed

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

2018-05-16

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

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

PubMed

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

2010-05-01

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

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

PubMed

Merchant, Anwar T; Pitiphat, Waranuch

2002-12-01

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

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

PubMed

Tong, I S; Lu, Y

2001-01-01

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

Intrafamilial aggregation and heritability of left ventricular geometric remodeling is independent of cardiac mass in families of African ancestry.

PubMed

Peterson, Vernice R; Norton, Gavin R; Redelinghuys, Michelle; Libhaber, Carlos D; Maseko, Muzi J; Majane, Olebogeng H I; Brooksbank, Richard; Woodiwiss, Angela J

2015-05-01

Whether left ventricular (LV) geometric remodeling, as indexed by relative wall thickness (RWT), aggregates in families and is inherited independent of LV mass (LVM) and additional confounders is uncertain. We determined whether RWT as assessed from 2D targeted M-mode echocardiography shows intrafamilial aggregation and heritability independent of LVM in 181 nuclear families (73 spouse pairs, 403 parent-child pairs, and 177 sibling-sibling pairs) with 16 families including 3 generations from an urban developing community of black Africans. Intrafamilial aggregation and heritability estimates (S.A.G.E. software) were assessed independent of confounders, including central aortic systolic blood pressure (SBPc) (radial applanation tonometry and SphygmoCor software). Independent of confounders including SBPc, LV RWT was correlated in parent-child (r = 0.32, P < 0.0001) and sibling-sibling (r = 0.29, P < 0.0001), but not in spouse (r = 0.11, P = 0.33) pairs. The relationships between parent-child (r = 0.28, P < 0.0001) and sibling-sibling (r = 0.24, P < 0.001) pairs persisted with further adjustments for LVM or LVM indexed to height(2.7) (LVMI). Similarly, independent of confounders, LV RWT showed significant heritability (h(2) ± SEM = 0.56 ± 0.09, P < 0.0001) and this persisted with further adjustments for LVM (h(2) ± SEM = 0.48 ± 0.09, P < 0.0001) or LVMI (h(2) ± SEM = 0.49 ± 0.09, P < 0.0001). In a group of African ancestry, independent of LVM, LV geometric remodeling shows significant intrafamilial aggregation and heritability. Genetic factors may in-part determine the LV geometric remodeling process independent of the extent of cardiac hypertrophy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2017-05-15

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

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

NASA Astrophysics Data System (ADS)

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

2013-04-01

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

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

PubMed

Larsson, Henrik

2016-04-01

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

Appropriate and inappropriate methods for investigating the "gateway" hypothesis, with a review of the evidence linking prior snus use to later cigarette smoking.

PubMed

Lee, Peter N

2015-03-20

The "gateway hypothesis" usually refers to the possibility that the taking up of habit A, which is considered harmless (or less harmful), may lead to the subsequent taking up of another habit, B, which is considered harmful (or more harmful). Possible approaches to designing and analysing studies to test the hypothesis are discussed. Evidence relating to the use of snus (A) as a gateway for smoking (B) is then evaluated in detail. The importance of having appropriate data available on the sequence of use of A and B and on other potential confounding factors that may lead to the taking up of B is emphasised. Where randomised trials are impractical, the preferred designs include the prospective cohort study in which ever use of A and of B is recorded at regular intervals, and the cross-sectional survey in which time of starting to use A and B is recorded. Both approaches allow time-stratified analytical methods to be used, in which, in each time period, risk of initiating B among never users of B at the start of the interval is compared according to prior use of A. Adjustment in analysis for the potential confounding factors is essential. Of 11 studies of possible relevance conducted in Sweden, Finland or Norway, only one seriously addresses potential confounding by those other factors involved in the initiation of smoking. Furthermore, 5 of the 11 studies are of a design that does not allow proper testing of the gateway hypothesis for various reasons, and the analysis is unsatisfactory, sometimes seriously, in all the remaining six. While better analyses could be attempted for some of the six studies identified as having appropriate design, the issues of confounding remain, and more studies are clearly needed. To obtain a rapid answer, a properly designed cross-sectional survey is recommended.

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2012-01-01

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

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; McCoy, Kathy D; Wullaert, Andy

2018-04-19

Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

Educational inequality in cardiovascular diseases: a sibling approach.

PubMed

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

2018-02-01

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

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

PubMed

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

2016-09-01

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

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

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

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

2007-07-01

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

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

PubMed

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

2011-06-01

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

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

PubMed

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

2017-11-22

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

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

PubMed

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

2016-12-01

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

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

PubMed

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

2013-10-01

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

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

PubMed

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

2017-06-26

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

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

PubMed

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

2013-02-01

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

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

PubMed Central

Gardener, Hannah; Buka, Stephen L.

2008-01-01

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

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.

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

PubMed

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

2002-04-01

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

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

PubMed

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

2016-01-01

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

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

PubMed

Wagner, Louis K

2014-10-01

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

State infant mortality: an ecologic study to determine modifiable risks and adjusted infant mortality rates.

PubMed

Paul, David A; Mackley, Amy; Locke, Robert G; Stefano, John L; Kroelinger, Charlan

2009-05-01

To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization procedures. Final risk adjusted IMR's were standardized and states were compared with the United States adjusted rates. Models for IMR in individual states in 2001 (r2 = 0.66, P < 0.01) and 2002 (r2 = 0.81, P < 0.01) were tested. African-American race, teen birth rate, and smoking during pregnancy remained independently associated with state infant mortality rates for 2001 and 2002. Ninety five percent confidence intervals (CI) were calculated around the regression lines to model the expected IMR. After adjustment, some states maintained a consistent IMR; for instance, Vermont and New Hampshire remained low, while Delaware and Louisiana remained high. However, other states such as Mississippi, which have traditionally high infant mortality rates, remained within the expected 95% CI for IMR after adjustment indicating confounding affected the initial unadjusted rates. Non-modifiable demographic variables, including the percentage of non-Hispanic African-American and Hispanic populations of the state are major factors contributing to individual variation in state IMR. Race and ethnicity may confound or modify the IMR in states that shifted inside or outside the 95% CI following adjustment. Other factors including smoking during pregnancy and teen birth rate, which are potentially modifiable, significantly contributed to differences in state IMR. State risk adjusted IMR indicate that other factors impact infant mortality after adjustment by race/ethnicity and other risk factors.

Arousal from sleep mechanisms in infants.

PubMed

Franco, Patricia; Kato, Ineko; Richardson, Heidi L; Yang, Joel S C; Montemitro, Enza; Horne, Rosemary S C

2010-08-01

Arousals from sleep allow sleep to continue in the face of stimuli that normally elicit responses during wakefulness and also permit awakening. Such an adaptive mechanism implies that any malfunction may have clinical importance. Inadequate control of arousal in infants and children is associated with a variety of sleep-related problems. An excessive propensity to arouse from sleep favors the development of repeated sleep disruptions and insomnia, with impairment of daytime alertness and performance. A lack of an adequate arousal response to a noxious nocturnal stimulus reduces an infant's chances of autoresuscitation, and thus survival, increasing the risk for Sudden Infant Death Syndrome (SIDS). The study of arousability is complicated by many factors including the definition of an arousal; the scoring methodology; the techniques used (spontaneous arousability versus arousal responses to endogenous or exogenous stimuli); and the confounding factors that complicate the determination of arousal thresholds by changing the sleeper's responses to a given stimulus such as prenatal drug, alcohol, or cigarette use. Infant age and previous sleep deprivation also modify thresholds. Other confounding factors include time of night, sleep stages, the sleeper's body position, and sleeping conditions. In this paper, we will review these different aspects for the study of arousals in infants and also report the importance of these studies for the understanding of the pathophysiology of some clinical conditions, particularly SIDS. Copyright 2010 Elsevier B.V. All rights reserved.

Changes in Landscape Greenness and Climatic Factors over ...

EPA Pesticide Factsheets

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

1998-06-01

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

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

PubMed Central

Källén, Bengt

2012-01-01

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

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

PubMed

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

2015-01-01

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

Spatial Variability of Geriatric Depression Risk in a High-Density City: A Data-Driven Socio-Environmental Vulnerability Mapping Approach.

PubMed

Ho, Hung Chak; Lau, Kevin Ka-Lun; Yu, Ruby; Wang, Dan; Woo, Jean; Kwok, Timothy Chi Yui; Ng, Edward

2017-08-31

Previous studies found a relationship between geriatric depression and social deprivation. However, most studies did not include environmental factors in the statistical models, introducing a bias to estimate geriatric depression risk because the urban environment was found to have significant associations with mental health. We developed a cross-sectional study with a binomial logistic regression to examine the geriatric depression risk of a high-density city based on five social vulnerability factors and four environmental measures. We constructed a socio-environmental vulnerability index by including the significant variables to map the geriatric depression risk in Hong Kong, a high-density city characterized by compact urban environment and high-rise buildings. Crude and adjusted odds ratios (ORs) of the variables were significantly different, indicating that both social and environmental variables should be included as confounding factors. For the comprehensive model controlled by all confounding factors, older adults who were of lower education had the highest geriatric depression risks (OR: 1.60 (1.21, 2.12)). Higher percentage of residential area and greater variation in building height within the neighborhood also contributed to geriatric depression risk in Hong Kong, while average building height had negative association with geriatric depression risk. In addition, the socio-environmental vulnerability index showed that higher scores were associated with higher geriatric depression risk at neighborhood scale. The results of mapping and cross-section model suggested that geriatric depression risk was associated with a compact living environment with low socio-economic conditions in historical urban areas in Hong Kong. In conclusion, our study found a significant difference in geriatric depression risk between unadjusted and adjusted models, suggesting the importance of including environmental factors in estimating geriatric depression risk. We also developed a framework to map geriatric depression risk across a city, which can be used for identifying neighborhoods with higher risk for public health surveillance and sustainable urban planning.

Spatial Variability of Geriatric Depression Risk in a High-Density City: A Data-Driven Socio-Environmental Vulnerability Mapping Approach

PubMed Central

Lau, Kevin Ka-Lun; Yu, Ruby; Wang, Dan; Kwok, Timothy Chi Yui; Ng, Edward

2017-01-01

Previous studies found a relationship between geriatric depression and social deprivation. However, most studies did not include environmental factors in the statistical models, introducing a bias to estimate geriatric depression risk because the urban environment was found to have significant associations with mental health. We developed a cross-sectional study with a binomial logistic regression to examine the geriatric depression risk of a high-density city based on five social vulnerability factors and four environmental measures. We constructed a socio-environmental vulnerability index by including the significant variables to map the geriatric depression risk in Hong Kong, a high-density city characterized by compact urban environment and high-rise buildings. Crude and adjusted odds ratios (ORs) of the variables were significantly different, indicating that both social and environmental variables should be included as confounding factors. For the comprehensive model controlled by all confounding factors, older adults who were of lower education had the highest geriatric depression risks (OR: 1.60 (1.21, 2.12)). Higher percentage of residential area and greater variation in building height within the neighborhood also contributed to geriatric depression risk in Hong Kong, while average building height had negative association with geriatric depression risk. In addition, the socio-environmental vulnerability index showed that higher scores were associated with higher geriatric depression risk at neighborhood scale. The results of mapping and cross-section model suggested that geriatric depression risk was associated with a compact living environment with low socio-economic conditions in historical urban areas in Hong Kong. In conclusion, our study found a significant difference in geriatric depression risk between unadjusted and adjusted models, suggesting the importance of including environmental factors in estimating geriatric depression risk. We also developed a framework to map geriatric depression risk across a city, which can be used for identifying neighborhoods with higher risk for public health surveillance and sustainable urban planning. PMID:28858265

An investigation into the relationship between age and physiological function in highly active older adults

PubMed Central

Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

2015-01-01

Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. Key Points The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55–79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. PMID:25565071

An investigation into the relationship between age and physiological function in highly active older adults.

PubMed

Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

2015-02-01

The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55-79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. V̇O2max was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55-79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption (V̇O2max) showed the closest association with age (r = -0.443 to -0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

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

PubMed

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

2004-07-01

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

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors.

PubMed

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-02-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations.

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

PubMed Central

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

2012-01-01

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

Carrying the pain of abuse: gender-specific findings on the relationship between childhood physical abuse and obesity in adulthood.

PubMed

Fuller-Thomson, Esme; Sinclair, Deborah A; Brennenstuhl, Sarah

2013-01-01

Childhood abuse has been associated with negative adult health outcomes, including obesity. This study sought to investigate the association between childhood physical abuse and adult obesity, while controlling for five clusters of potentially confounding factors: childhood stressors, socioeconomic indicators, marital status, health behaviors, and mental health. Representative data from the 2005 Canadian Community Health Survey were selected. The response rate was approximately 84%. Gender-specific logistic regression analyses determined the association between abuse and obesity, while controlling for age and race and five clusters of potentially confounding factors. Of the 12,590 respondents with complete data, 2,787 were obese and 976 reported physical abuse as a child or adolescent by someone close to them. Among women with childhood physical abuse compared to no abuse, the odds of obesity were 35% higher, even when controlling for age, race, and the five clusters of factors (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 1.09, 1.67). Childhood physical abuse was not associated with adult obesity among men (OR = 1.12; 95% CI = 0.82, 1.53). This study provides one of the first population-based, gender-specific analyses of the association between childhood physical abuse and obesity controlling for a wide range of factors. The gender-specific findings require further exploration.

On the Influence of Confounding Factors in Multisite Brain Morphometry Studies of Developmental Pathologies: Application to Autism Spectrum Disorder.

PubMed

Auzias, G; Takerkart, S; Deruelle, C

2016-05-01

Pooling data acquired on different MR scanners is a commonly used practice to increase the statistical power of studies based on MRI-derived measurements. Such studies are very appealing since they should make it possible to detect more subtle effects related to pathologies. However, the influence of confounds introduced by scanner-related variations remains unclear. When studying brain morphometry descriptors, it is crucial to investigate whether scanner-induced errors can exceed the effect of the disease itself. More specifically, in the context of developmental pathologies such as autism spectrum disorders (ASD), it is essential to evaluate the influence of the scanner on age-related effects. In this paper, we studied a dataset composed of 159 anatomical MR images pooled from three different scanners, including 75 ASD patients and 84 healthy controls. We quantitatively assessed the effects of the age, pathology, and scanner factors on cortical thickness measurements. Our results indicate that scan pooling from different sites would be less fruitful in some cortical regions than in others. Although the effect of age is consistent across scanners, the interaction between the age and scanner factors is important and significant in some specific cortical areas.

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

PubMed Central

2013-01-01

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

Leiomyomas in Pregnancy and Spontaneous Abortion: A Systematic Review and Meta-analysis.

PubMed

Sundermann, Alexandra C; Velez Edwards, Digna R; Bray, Michael J; Jones, Sarah H; Latham, Sanura M; Hartmann, Katherine E

2017-11-01

To systematically review studies reporting the risk of spontaneous abortion among pregnant women of typical reproductive potential with and without uterine leiomyomas. We searched PubMed, EMBASE, Web of Science, and ClinicalTrials.gov for publications from January 1970 to December 2016. We excluded studies that did not use imaging to uniformly document leiomyoma status of all participants, did not have a comparison group without leiomyomas, or primarily included women seeking care for recurrent miscarriage, infertility care, or assisted reproductive technologies. Two authors independently reviewed eligibility, extracted data, and assigned overall quality ratings based on predetermined criteria. Of 1,469 articles identified, nine were eligible. Five enrolled general obstetric populations and four included women undergoing amniocentesis. In five studies in general obstetric populations that included 21,829 pregnancies (1,394 women with leiomyomas and 20,435 without), only one adjusted for potential confounders. This meta-analysis revealed no increase in risk of spontaneous abortion among those with leiomyomas compared with those without (11.5% compared with 8.0%; risk ratio 1.16, 95% CI 0.80-1.52). When bias from confounding was estimated for nonadjusted studies, the aggregate calculated risk ratio was 0.83 (95% CI 0.68-0.98). Leiomyoma presence was not associated with increased risk of spontaneous abortion in an analysis of more than 20,000 pregnant women. Failure of prior studies to adjust for confounders may have led to the common clinical belief that leiomyomas are a risk factor for spontaneous abortion.

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

USDA-ARS?s Scientific Manuscript database

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

Risk Factors in Adolescent Hypertension

PubMed Central

Ewald, D. Rose; Haldeman, Lauren A.

2016-01-01

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

Prenatal depression effects and interventions: a review.

PubMed

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

2010-12-01

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

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

PubMed

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

2018-05-01

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

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

PubMed

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

2016-06-01

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

Pattern identification in time-course gene expression data with the CoGAPS matrix factorization.

PubMed

Fertig, Elana J; Stein-O'Brien, Genevieve; Jaffe, Andrew; Colantuoni, Carlo

2014-01-01

Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset.

Addressing unmeasured confounding in comparative observational research.

PubMed

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

2018-04-01

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

Complexities of sibling analysis when exposures and outcomes change with time and birth order.

PubMed

Sudan, Madhuri; Kheifets, Leeka I; Arah, Onyebuchi A; Divan, Hozefa A; Olsen, Jørn

2014-01-01

In this study, we demonstrate the complexities of performing a sibling analysis with a re-examination of associations between cell phone exposures and behavioral problems observed previously in the Danish National Birth Cohort. Children (52,680; including 5441 siblings) followed up to age 7 were included. We examined differences in exposures and behavioral problems between siblings and non-siblings and by birth order and birth year. We estimated associations between cell phone exposures and behavioral problems while accounting for the random family effect among siblings. The association of behavioral problems with both prenatal and postnatal exposure differed between siblings (odds ratio (OR): 1.07; 95% confidence interval (CI): 0.69-1.66) and non-siblings (OR: 1.54; 95% CI: 1.36-1.74) and within siblings by birth order; the association was strongest for first-born siblings (OR: 1.72; 95% CI: 0.86-3.42) and negative for later-born siblings (OR: 0.63; 95% CI: 0.31-1.25), which may be because of increases in cell phone use with later birth year. Sibling analysis can be a powerful tool for (partially) accounting for confounding by invariant unmeasured within-family factors, but it cannot account for uncontrolled confounding by varying family-level factors, such as those that vary with time and birth order.

Comparable risk of childhood asthma after vaginal delivery and emergency caesarean section.

PubMed

Brix, Nis; Stokholm, Lonny; Jonsdottir, Fjola; Kristensen, Kim; Secher, Niels Jørgen

2017-01-01

Caesarean section is thought to be a risk factor for childhood asthma, but this association may be caused by confounding from, for instance, familial factors. To address this problem, we used twin pairs to assess the risk of childhood asthma after emergency caesarean section. The study was a register-based nation-wide matched cohort study using twin pairs to minimise residual confounding. Included were twin pairs in which the first twin was delivered vaginally and the second by emergency caesarean section during the study period from January 1997 through December 2012. In total, 464 twin pairs (928 twins) were included. In 30 pairs, the first twin (vaginal delivery) was diagnosed with asthma, but the second twin (emergency caesarean section) was not. In 20 pairs, the second twin (emergency caesarean section) was diagnosed with asthma, but the first twin (vaginal delivery) was not. In 11 pairs, both twins developed asthma. In the unadjusted analysis, emergency caesarean section did not affect the risk of asthma (odds ratio = 0.67 (95% confidence interval: 0.38-1.17); p = 0.16). After adjusting for birth weight, gender, umbilical cord pH, Apgar score at 5 min. and neonatal respiratory morbidity, the risk of childhood asthma following emergency caesarean section remained unchanged. Emergency caesarean section was not associated with childhood asthma. none. not relevant.

Vegetarian diets and depressive symptoms among men.

PubMed

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.

Lung cancer and diesel exhaust: an updated critical review of the occupational epidemiology literature.

PubMed

Gamble, John F; Nicolich, Mark J; Boffetta, Paolo

2012-08-01

A recent review concluded that the evidence from epidemiology studies was indeterminate and that additional studies were required to support the diesel exhaust-lung cancer hypothesis. This updated review includes seven recent studies. Two population-based studies concluded that significant exposure-response (E-R) trends between cumulative diesel exhaust and lung cancer were unlikely to be entirely explained by bias or confounding. Those studies have quality data on life-style risk factors, but do not allow definitive conclusions because of inconsistent E-R trends, qualitative exposure estimates and exposure misclassification (insufficient latency based on job title), and selection bias from low participation rates. Non-definitive results are consistent with the larger body of population studies. An NCI/NIOSH cohort mortality and nested case-control study of non-metal miners have some surrogate-based quantitative diesel exposure estimates (including highest exposure measured as respirable elemental carbon (REC) in the workplace) and smoking histories. The authors concluded that diesel exhaust may cause lung cancer. Nonetheless, the results are non-definitive because the conclusions are based on E-R patterns where high exposures were deleted to achieve significant results, where a posteriori adjustments were made to augment results, and where inappropriate adjustments were made for the "negative confounding" effects of smoking even though current smoking was not associated with diesel exposure and therefore could not be a confounder. Three cohort studies of bus drivers and truck drivers are in effect air pollution studies without estimates of diesel exhaust exposure and so are not sufficient for assessing the lung cancer-diesel exhaust hypothesis. Results from all occupational cohort studies with quantitative estimates of exposure have limitations, including weak and inconsistent E-R associations that could be explained by bias, confounding or chance, exposure misclassification, and often inadequate latency. In sum, the weight of evidence is considered inadequate to confirm the diesel-lung cancer hypothesis.

Chronic prostatitis and comorbid non-urological overlapping pain conditions: A co-twin control study.

PubMed

Gasperi, Marianna; Krieger, John N; Forsberg, Christopher; Goldberg, Jack; Buchwald, Dedra; Afari, Niloofar

2017-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs. Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations. There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome. CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities. Published by Elsevier Inc.

Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases.

PubMed

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.

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

PubMed

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

2018-01-01

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

phMRI: methodological considerations for mitigating potential confounding factors

PubMed Central

Bourke, Julius H.; Wall, Matthew B.

2015-01-01

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

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

ERIC Educational Resources Information Center

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

2018-01-01

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

Abortion in young women and subsequent mental health.

PubMed

Fergusson, David M; Horwood, L John; Ridder, Elizabeth M

2006-01-01

The extent to which abortion has harmful consequences for mental health remains controversial. We aimed to examine the linkages between having an abortion and mental health outcomes over the interval from age 15-25 years. Data were gathered as part of the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of New Zealand children. Information was obtained on: a) the history of pregnancy/abortion for female participants over the interval from 15-25 years; b) measures of DSM-IV mental disorders and suicidal behaviour over the intervals 15-18, 18-21 and 21-25 years; and c) childhood, family and related confounding factors. Forty-one percent of women had become pregnant on at least one occasion prior to age 25, with 14.6% having an abortion. Those having an abortion had elevated rates of subsequent mental health problems including depression, anxiety, suicidal behaviours and substance use disorders. This association persisted after adjustment for confounding factors. The findings suggest that abortion in young women may be associated with increased risks of mental health problems.

Single living predicts a higher mortality in both women and men with chronic heart failure.

PubMed

Mard, Shan; Nielsen, Finn Erland

2016-09-01

We examined the impact of single living on all-cause mortality in patients with chronic heart failure and determined if this association was modified by gender. This historical cohort study included 637 patients who were admitted to the Department of Cardiology, Herlev Hospital, Denmark, between 1 July 2005 and 30 June 2007. Baseline clinical data were obtained from patient records. Data on survival rates were obtained from the Danish Civil Registration System. Cox proportional hazard analysis was used to compute the hazard ratio (HR) of all-cause mortality, controlling for confounding factors. The median follow-up time was 2.8 years. A total of 323 (50.7%) patients died during the follow-up period. After adjustment for confounding factors, risk of death was associated with being single (HR = 1.53 (95% confidence interval: 1.19-1.96)). In a gender-stratified analysis, the risk of death did not differ among single-living women and men. Single living is a prognostic determinant of all-cause mortality in men and women with chronic heart failure. none. not relevant.

Reliability of conditioned pain modulation: a systematic review

PubMed Central

Kennedy, Donna L.; Kemp, Harriet I.; Ridout, Deborah; Yarnitsky, David; Rice, Andrew S.C.

2016-01-01

Abstract A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational studies of the repeatability of a CPM test paradigm in adult humans were included. Two independent reviewers assessed the risk of bias in 6 domains; study participation; study attrition; prognostic factor measurement; outcome measurement; confounding and analysis using the Quality in Prognosis Studies (QUIPS) critical assessment tool. Intraclass correlation coefficients (ICCs) less than 0.4 were considered to be poor; 0.4 and 0.59 to be fair; 0.6 and 0.75 good and greater than 0.75 excellent. Ten studies were included in the final review. Meta-analysis was not appropriate because of differences between studies. The intersession reliability of the CPM effect was investigated in 8 studies and reported as good (ICC = 0.6-0.75) in 3 studies and excellent (ICC > 0.75) in subgroups in 2 of those 3. The assessment of risk of bias demonstrated that reporting is not comprehensive for the description of sample demographics, recruitment strategy, and study attrition. The absence of blinding, a lack of control for confounding factors, and lack of standardisation in statistical analysis are common. Conditioned pain modulation is a reliable measure; however, the degree of reliability is heavily dependent on stimulation parameters and study methodology and this warrants consideration for investigators. The validation of CPM as a robust prognostic factor in experimental and clinical pain studies may be facilitated by improvements in the reporting of CPM reliability studies. PMID:27559835

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

PubMed

Schmidt, Stephen G

2016-07-01

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

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

PubMed Central

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

2016-01-01

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

Supervised normalization of microarrays

PubMed Central

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

2010-01-01

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

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

PubMed

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

2018-05-01

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

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

PubMed

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

2017-05-01

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

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

PubMed

Lynch, Wendy D; Sherman, Bruce W

2014-01-01

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

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

PubMed Central

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

2011-01-01

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

Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor.

PubMed

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J; Tesfaye, Solomon

2010-01-01

To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN.

Prevalence and associated factors for temporomandibular disorders in Chinese civilian pilots.

PubMed

Yu, Qing; Liu, Yang; Chen, Xi; Chen, Duanjing; Xie, Lu; Hong, Xiao; Wang, Xingyuan; Huang, Haili; Yu, Haiyang

2015-10-01

Piloting is a special profession with prolonged stress, which could induce the occurrence of TMD. This sample is useful to reduce the effect of confounders in the analyses. Based on this, the present study aims to determine the prevalence and associated factors for TMD in civilian pilots of China. A cross-sectional epidemiological survey was carried out in 616 male subjects (aged 23-52 years). The questionnaire included general information, chewing preference (bilateral or unilateral), and Trait Anxiety section of Spielberger State-Trait Anxiety Inventory (STAI-T). The clinical examination contained TMD screening per research diagnostic criteria for TMD and diagnosis of sleep bruxism per American Academy of Sleep Medicine standards. The level of statistical significance was set at P ≤ 0.05. The program was conducted from June 2012 to April 2013, in which period, and the percentage of TMD in the samples we examined was 33.3 % (=205/616). Only high anxiety (OR 2.48; 95 % CI 1.25-4.90) and unilateral chewing preference (OR 12.67; 95 % CI 7.77-20.65) were the most significant associated factors with TMD. Also, salivary cortisol and the STAI-T score had a significant correlation (r = 0.47, P < 0.001). It was more reliable to study the associated factors on TMD with the exclusion of the possible confounding factors, and only unilateral chewing preference and psychological stress had a significant association with TMD. In addition, the salivary cortisol levels might assist to assess psychological stress in epidemiological research.

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

PubMed Central

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

2010-01-01

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

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

PubMed

Tillmann, Taavi; Pikhart, Hynek; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Malyutina, Sofia; Steptoe, Andrew; Kivimäki, Mika; Marmot, Michael; Bobak, Martin

2017-12-01

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

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

PubMed Central

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

2017-01-01

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

Violent behavior and aggression in schizophrenia: Prevalence and risk factors. A multicentric study from three Latin-America countries.

PubMed

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.

Empowerment of women and its association with the health of the community.

PubMed

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

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

PubMed

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

2016-01-01

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

Robustness of meta-analyses in finding gene × environment interactions

PubMed Central

Shi, Gang; Nehorai, Arye

2017-01-01

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

Birth Weight, Physical Morbidity, and Mortality: A Population-based Sibling-Comparison Study

PubMed Central

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

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

PubMed

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

2013-09-01

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

Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders

PubMed Central

Hagihara, Hideo; Catts, Vibeke S; Katayama, Yuta; Shoji, Hirotaka; Takagi, Tsuyoshi; Huang, Freesia L; Nakao, Akito; Mori, Yasuo; Huang, Kuo-Ping; Ishii, Shunsuke; Graef, Isabella A; Nakayama, Keiichi I; Shannon Weickert, Cynthia; Miyakawa, Tsuyoshi

2018-01-01

Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder. PMID:28776581

Associations between poor sleep quality and psychosocial stress with obesity in reproductive-age women of lower socioeconomic status.

PubMed

Tom, Sarah E; Berenson, Abbey B

2013-01-01

Prior studies have not examined the role of psychosocial stress in the relationship between poor sleep quality and obesity among women of lower socioeconomic status (SES). We tested the following hypotheses in a sample of reproductive-age women of lower SES: 1) Poor sleep quality is related to increased risk of obesity, and 2) psychosocial stress confounds this association between poor sleep quality and obesity. A total of 927 women age 16 to 40 years attending public health clinics in Southeastern Texas provided information on the Pittsburgh Sleep Quality Index and sociodemographic and health characteristics, including the Perceived Stress Scale. Height, weight, and waist circumference (WC) were measured in clinic. A series of models examined the associations between sleep disturbance, perceived stress, and weight outcomes, accounting for potential confounding factors. Nearly 30% of women were overweight, and 35% were obese. Half of women had a WC of greater than 35 inches. Most women had poor sleep quality and high levels of stress. Sleep quality and perceived stress were not related to body mass index category or WC in models that adjusted for age and race/ethnicity. Adjusting for potential confounding factors did not alter results. Perceived stress did not modify the association between sleep quality and weight outcomes. Poor sleep quality and psychosocial stress were not related to weight in reproductive-aged women of lower SES. However, poor sleep quality, high stress, overweight, and obesity were common in this group. Copyright © 2013 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Synergistic and Non-synergistic Associations for Cigarette Smoking and Non-tobacco Risk Factors for Cardiovascular Disease Incidence in the Atherosclerosis Risk In Communities (ARIC) Study.

PubMed

Lubin, Jay H; Couper, David; Lutsey, Pamela L; Yatsuya, Hiroshi

2017-07-01

Cigarette smoking, various metabolic and lipid-related factors and hypertension are well-recognized cardiovascular disease (CVD) risk factors. Since smoking affects many of these factors, use of a single imprecise smoking metric, for example, ever or never smoked, may allow residual confounding and explain inconsistencies in current assessments of interactions. Using a comprehensive model in pack-years and cigarettes/day for the complex smoking-related relative risk (RR) of CVD to reduce residual confounding, we evaluated interactions with non-tobacco risk factors, including additive (non-synergistic) and multiplicative (synergistic) forms. Data were from the prospective Atherosclerosis Risk in Communities (ARIC) Study from four areas of the United States recruited in 1987-1989 with follow-up through 2008. Analyses included 14 127 participants, 207 693 person-years and 2857 CVD events. Analyses revealed distinct interactions with smoking: including statistical consistency with additive (body mass index [BMI], waist to hip ratio [WHR], diabetes mellitus [DM], glucose, insulin, high density lipoproteins [HDL] and HDL(2)); and multiplicative (hypertension, total cholesterol [TC], low density lipoproteins [LDLs], apolipoprotein B [apoB], TC to HDL ratio and HDL(3)) associations, as well as indeterminate (apolipoprotein A-I [apoA-I] and triglycerides) associations. The forms of the interactions were revealing but require confirmation. Improved understanding of joint associations may help clarify the public health burden of smoking for CVD, links between etiologic factors and biological mechanisms, and the consequences of joint exposures, whereby synergistic associations highlight joint effects and non-synergistic associations suggest distinct contributions. Joint associations for cigarette smoking and non-tobacco risk factors were distinct, revealing synergistic/multiplicative (hypertension, TC, LDL, apoB, TC/HDL, HDL(3)), non-synergistic/additive (BMI, WHR, DM, glucose, insulin, HDL, HDL(2)) and indeterminate (apoA-I and TRIG) associations. If confirmed, these results may help better define the public health burden of smoking on CVD risk and identify links between etiologic factors and biologic mechanisms, where synergistic associations highlight joint impacts and non-synergistic associations suggest distinct contributions from each factor. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: a prospective cohort study.

PubMed

Linnet, Karen Markussen; Wisborg, Kirsten; Secher, Niels Jørgen; Thomsen, Per Hove; Obel, Carsten; Dalsgaard, Søren; Henriksen, Tine Brink

2009-01-01

Based on hypotheses from experimental studies, we studied the association between intrauterine exposure to coffee and the risk of clinically verified hyperkinetic disorder and attention-deficit hyperactivity disorder (ADHD). A cohort study with prospectively collected data from the Aarhus Birth Cohort, Denmark. We included 24 068 singletons delivered between 1990 and 1998. Linkage was performed with three Danish longitudinal registers: The Danish Psychiatric Central Register, The Integrated Database for Labour Market Research and The Danish Civil Registration System. We identified 88 children with hyperkinetic disorder and ADHD. Information about coffee consumption during pregnancy was obtained at 16 weeks of gestation from self-administrated questionnaires. Potential confounding factors were evaluated using Cox regression analyses. We found that intrauterine exposure to 10 or more cups of coffee per day was associated with a threefold increased risk of hyperkinetic disorder and ADHD. After adjustments for a number of confounding factors, the risk decreased and became statistically insignificant (RR 2.3, 95% CI 0.9-5.9). Prenatal exposure to high levels of coffee did not significantly increase the risk of clinically verified hyperkinetic disorder and ADHD in childhood.

Pattern classification of brain activation during emotional processing in subclinical depression: psychosis proneness as potential confounding factor.

PubMed

Modinos, Gemma; Mechelli, Andrea; Pettersson-Yeo, William; Allen, Paul; McGuire, Philip; Aleman, Andre

2013-01-01

We used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in healthy participants with subclinical depressive symptoms. Six-hundred undergraduate students completed the Beck Depression Inventory II (BDI-II). Two groups were subsequently formed: (i) subclinical (mild) mood disturbance (n = 17) and (ii) no mood disturbance (n = 17). Participants also completed a self-report questionnaire on subclinical psychotic symptoms, the Community Assessment of Psychic Experiences Questionnaire (CAPE) positive subscale. The functional magnetic resonance imaging (fMRI) paradigm entailed passive viewing of negative emotional and neutral scenes. The pattern of brain activity during emotional processing allowed correct group classification with an overall accuracy of 77% (p = 0.002), within a network of regions including the amygdala, insula, anterior cingulate cortex and medial prefrontal cortex. However, further analysis suggested that the classification accuracy could also be explained by subclinical psychotic symptom scores (correlation with SVM weights r = 0.459, p = 0.006). Psychosis proneness may thus be a confounding factor for neuroimaging studies in subclinical depression.

Tea and Cardiovascular Disease

PubMed Central

Deka, Apranta; Vita, Joseph A.

2011-01-01

There is increasing evidence for a protective effect of tea consumption against cardiovascular disease. This review summarizes the available epidemiological data providing evidence for and against such an effect. We also review observational and intervention studies that investigated an effect of tea and tea extracts on cardiovascular risk factors, including blood pressure, serum lipids, diabetes mellitus, and obesity. Finally, we review potential mechanisms of benefit, including anti-inflammatory, anti-oxidant, and anti-proliferative effects, as well as favorable effects on endothelial function. Overall, the observational data suggest a benefit, but results are mixed and likely confounded by lifestyle and background dietary factors. The weight of evidence indicates favorable effects on risk factors and a number of plausible mechanisms have been elucidated in experimental and translational human studies. Despite the growing body evidence, it remains uncertain whether tea consumption should be recommended to the general population or to patients as a strategy to reduce cardiovascular risk. PMID:21477653

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

PubMed

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

2012-11-01

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

Risk of Retinal Artery Occlusion in Patients With End-Stage Renal Disease

PubMed Central

Chang, Yuh-Shin; Weng, Shih-Feng; Chang, Chun; Wang, Jhi-Joung; Tseng, Sung-Huei; Ko, Shun-Yao; Su, Shih-Bin; Huang, Chien-Cheng; Wang, Jiu-Yao; Jan, Ren-Long

2016-01-01

Abstract There is globally increasing prevalence and incidence in end-stage renal disease (ESRD). These patients are frequently reported to have retinal abnormalities and both diseases share some systemic risk factors. Hence, it is clinically relevant to determine whether ESRD is a predictor of retinal artery occlusion (RAO). To investigate the risk of RAO in ESRD patients. A retrospective, nationwide, matched cohort study. The study included 93,766 ESRD patients recruited between 2000 and 2009 from the Taiwan National Health Insurance Research Database. The same number control group included age- and sex-matched patients without ESRD selected from the Taiwan Longitudinal Health Insurance Database, 2000. Data for each patient were collected from the index date until December 2011. The incidence and risk of RAO were compared between the 2 groups. The hazard ratio (HR) for RAO after adjustment for potential confounders was calculated using Cox proportional hazards regression. Kaplan–Meier analysis was used to calculate the cumulative RAO incidence rate. In total, 237 ESRD patients and 73 controls exhibited RAO during follow-up; thus, the RAO incidence rate in ESRD patients was 4.49 times (95% confidence interval (CI), 3.45–5.83) that in the control patients. After adjustment for potential confounders, including diabetes mellitus, hypertension, hyperlipidemia, congestive heart failure, and coronary artery disease, ESRD patients were 2.78 times (95% CI, 2.02–3.84) more likely to develop RAO in cohort for the total sample. Among patients with hypertension, the RAO incidence rate was significantly higher in the ESRD group, and hypertension significantly increased RAO risk even after adjustment for other confounders in the cohort. ESRD increases the risk of RAO, particularly in ESRD patients with hypertension. Therefore, clinicians should educate ESRD patients about RAO and ensure appropriate blood pressure control. PMID:27057891

Risk of Retinal Artery Occlusion in Patients With End-Stage Renal Disease: A Retrospective Large-Scale Cohort Study.

PubMed

Chang, Yuh-Shin; Weng, Shih-Feng; Chang, Chun; Wang, Jhi-Joung; Tseng, Sung-Huei; Ko, Shun-Yao; Su, Shih-Bin; Huang, Chien-Cheng; Wang, Jiu-Yao; Jan, Ren-Long

2016-04-01

There is globally increasing prevalence and incidence in end-stage renal disease (ESRD). These patients are frequently reported to have retinal abnormalities and both diseases share some systemic risk factors. Hence, it is clinically relevant to determine whether ESRD is a predictor of retinal artery occlusion (RAO).To investigate the risk of RAO in ESRD patients.A retrospective, nationwide, matched cohort study. The study included 93,766 ESRD patients recruited between 2000 and 2009 from the Taiwan National Health Insurance Research Database. The same number control group included age- and sex-matched patients without ESRD selected from the Taiwan Longitudinal Health Insurance Database, 2000. Data for each patient were collected from the index date until December 2011.The incidence and risk of RAO were compared between the 2 groups. The hazard ratio (HR) for RAO after adjustment for potential confounders was calculated using Cox proportional hazards regression. Kaplan-Meier analysis was used to calculate the cumulative RAO incidence rate.In total, 237 ESRD patients and 73 controls exhibited RAO during follow-up; thus, the RAO incidence rate in ESRD patients was 4.49 times (95% confidence interval (CI), 3.45-5.83) that in the control patients. After adjustment for potential confounders, including diabetes mellitus, hypertension, hyperlipidemia, congestive heart failure, and coronary artery disease, ESRD patients were 2.78 times (95% CI, 2.02-3.84) more likely to develop RAO in cohort for the total sample. Among patients with hypertension, the RAO incidence rate was significantly higher in the ESRD group, and hypertension significantly increased RAO risk even after adjustment for other confounders in the cohort.ESRD increases the risk of RAO, particularly in ESRD patients with hypertension. Therefore, clinicians should educate ESRD patients about RAO and ensure appropriate blood pressure control.

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

PubMed

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

2016-08-16

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

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

PubMed Central

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

2017-01-01

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

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

PubMed Central

Durbin, Richard; Winn, John

2010-01-01

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

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

PubMed

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

2011-07-01

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

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

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

Fayerweather, W.E.

2007-07-01

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

Urinary excretion of mutagens in coke oven workers.

PubMed

Clonfero, E; Granella, M; Marchioro, M; Barra, E L; Nardini, B; Ferri, G; Foà, V

1995-03-01

The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). Multiple regression analysis showed that the mutagenic potency of urinary extracts of coke oven workers depended on exposure to PAHs, tobacco smoking habits, and consumption of fried, grilled or barbecued meat. Increased urinary mutagenic activity strengthens epidemiological evidence of the increased risk of renal and urinary tract tumours in these workers. The presence of mutagenic metabolites in urine as a result of occupational exposure to PAH may be demonstrated only by using highly sensitive techniques for assessing urinary mutagenic activity in studies which include careful checking of the main confounding factors.

The Effects of a Nutrient-Enriched Bar on Host Defense Mechanisms and Immunogenicity of Hepatitis A Vaccine During US Army Ranger Training

DTIC Science & Technology

2000-02-01

from casein and soy and carbohydrates from honey, maltodextrin, and high fructose corn syrup . The treatment bar contained fructooligosaccharide (an...nutritional deprivation and immune dysregulation as measured by a high rate of skin DTH anergy among trainees (58). However, even with severe energy...same amount of energy was included in the placebo bar to prevent any confounding factors. The bars contained similar proteins ( high biologic value

Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors.

PubMed

Campos, Carlos; Rocha, Nuno Barbosa F; Lattari, Eduardo; Paes, Flávia; Nardi, António E; Machado, Sérgio

2016-06-01

Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials.

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

PubMed

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

2012-08-01

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

Winter birth, urbanicity and immigrant status predict psychometric schizotypy dimensions in adolescents.

PubMed

Mimarakis, D; Roumeliotaki, T; Roussos, P; Giakoumaki, S G; Bitsios, P

2018-01-01

Urbanicity, immigration and winter-birth are stable epidemiological risk factors for schizophrenia, but their relationship to schizotypy is unknown. This is a first examination of the association of these epidemiological risk factors with positive schizotypy, in nonclinical adolescents, controlling for a range of potential and known confounders. We collected socio-demographics, life-style, family and school circumstances, positive schizotypy dimensions and other personality traits from 445 high school pupils (192 males, 158 immigrants) from 9 municipalities in Athens and Heraklion, Greece, which covered a range of host population and migrant densities. Using multivariate hierarchical linear regressions models, we estimated the association of schizotypy dimensions with: (1) demographics of a priori interest (winter-birth, immigrant status, urban characteristics), including family financial and mental health status; (2) factors resulting from principal component analysis (PCA) of the demographic and personal data; (3) factors resulting from PCA of the personality questionnaires. Adolescent women scored higher on schizotypy than men. High anxiety/neuroticism was the most consistent and significant predictor of all schizotypy dimensions in both sexes. In the fully adjusted models, urbanicity predicted magical thinking and unusual experiences in women, while winter-birth and immigration predicted paranoid ideation and unusual experiences respectively in men. These results support the continuum hypothesis and offer potential insights in the nature of risk conferred by winter-birth, urbanicity and immigration and the nature of important sex differences. Controlling for a wide range of potential confounding factors increases the robustness of these results and confidence that these were not spurious associations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The association between depression and emotional and social loneliness in older persons and the influence of social support, cognitive functioning and personality: A cross-sectional study.

PubMed

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.

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

PubMed

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

2010-11-05

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

Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study

PubMed Central

O’Neill, Sinéad M.; Curran, Eileen A.; Dalman, Christina; Kenny, Louise C.; Kearney, Patricia M.; Clarke, Gerard; Cryan, John F.; Dinan, Timothy G.; Khashan, Ali S.

2016-01-01

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n = 1 345 210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ2 for heterogeneity P = .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment. PMID:26615187

Relationship of type of work with health-related quality of life.

PubMed

Kawabe, Yuri; Nakamura, Yasuyuki; Kikuchi, Sayuri; Suzukamo, Yoshimi; Murakami, Yoshitaka; Tanaka, Taichiro; Takebayashi, Toru; Okayama, Akira; Miura, Katsuyuki; Okamura, Tomonori; Fukuhara, Shunichi; Ueshima, Hirotsugu

2015-12-01

To examine the relation of work type with health-related quality of life (HRQoL) in healthy workers. We cross-sectionally examined 4427 (3605 men and 822 women) healthy workers in Japan, aged 19-69 years. We assessed HRQoL based on scores for five scales of the SF-36. Multiple regression was applied to examine the relation of work type (nighttime, shift, day to night, and daytime) with the five HRQoL norm-based scores, lower scores of which indicate poorer health status, adjusted for confounding factors, including sleeping duration. Shiftwork was inversely related to role physical [regression estimate (β) = -2.12, 95 % confidence intervals (CI) -2.94, -1.30, P < 0.001], general health (β = -1.37, 95 % CI -2.01, -0.72, P < 0.001), role emotional (β = -1.24, 95% CI -1.98, -0.50, P < 0.001), and mental health (β = -1.31, 95% CI -2.01, -0.63, P < 0.001) independent of confounding factors, but not to vitality. Day-to-nighttime work was inversely related to all the five HRQoL subscales (Ps 0.012 to <0.001). Shiftwork was significantly inversely related to four out of the five HRQoL, except for vitality, and day-to-nighttime work was significantly inversely related to all five HRQoL, independent of demographic and lifestyle factors.

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

PubMed Central

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

2016-01-01

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

Association of fasting triglyceride concentration and postprandial triglyceride response with the carotid intima-media thickness in the middle aged: The Netherlands Epidemiology of Obesity study.

PubMed

Christen, Tim; de Mutsert, Renée; Gast, Karin B; Rensen, Patrick C N; de Koning, Eelco; Rosendaal, Frits R; Trompet, Stella; Jukema, J Wouter

People are in a postprandial state for the majority of the day, postprandial triglyceride (TG) response may be more important in the etiology of atherosclerosis than fasting TGs. The objective of the study was to investigate the associations of fasting TG concentration (TGc) and postprandial TG response after a meal challenge with subclinical atherosclerosis, measured by intima-media thickness (IMT) in a middle-aged population. A total of 5574 participants (57% women) with a mean (standard deviation [SD]) age of 56 (6) years were included in this cross-sectional analysis of baseline measurements of The Netherlands Epidemiology of Obesity study. Serum TGc was measured fasting and 30 and 150 minutes after a liquid mixed meal, and the incremental area under the curve (TGiAUC) was calculated. With linear regression analyses, we calculated the differences in IMT with 95% confidence intervals, adjusted for confounding factors, and additionally for TGc or TGiAUC. Per SD of TGc (0.82 mmol/L), IMT was 8.5 μm (2.1, 14.9) greater after adjustment for TGiAUC and confounding factors. Per SD of TGiAUC (24.0 mmol/L × min), the difference in IMT was -1.7 μm (-8.5, 5.0) after adjustment for fasting TG and confounding factors. The association between TG response after a mixed meal and IMT disappeared after adjusting for TGc. The association between fasting TG concentration and IMT persisted after adjustment for postprandial TG response. These findings imply that it is not useful to perform a meal challenge in cardiovascular risk stratification. Our results support use of fasting TGc instead of postprandial TG responses for cardiovascular risk stratification in clinical practice. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Peer influence as a potential magnifier of ADHD diagnosis.

PubMed

Aronson, Brian

2016-11-01

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

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

PubMed

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

2017-10-01

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

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

PubMed Central

Perin, Jamie; Walker, Neff

2015-01-01

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

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

PubMed

Perin, Jamie; Walker, Neff

2015-01-01

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

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

PubMed

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

2016-11-01

Between 2001 and 2010, six research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries to estimate exposure-response relationships. This analysis examined the presence and magnitude of confounding between biomechanical and workplace psychosocial factors and incidence of dominant-hand CTS. 1605 participants, without CTS at enrolment, were followed for up to 3.5 years (2471 person-years). Demographic information, medical history and workplace psychosocial stress measures were collected at baseline. Individual workplace biomechanical exposures were collected for each task and combined across the workweek using time-weighted averaging (TWA). CTS case criteria were based on symptoms and results of electrophysiological testing. HRs were estimated with Cox proportional hazard models. Confounding was assessed using causal diagrams and an empirical criterion of 10% or greater change in effect estimate magnitude. There were 109 incident CTS cases (IR=4.41/100 person-years; 6.7% cumulative incidence). The relationships between CTS and forceful repetition rate, % time forceful hand exertion and the Threshold Limit Value for Hand Activity Level (TLV-HAL) were slightly confounded by decision latitude with effect estimates being attenuated towards the null (10-14% change) after adjustment. The risk of CTS among participants reporting high job strain was attenuated towards the null by 14% after adjusting for the HAL Scale or the % time forceful hand exertions. Although attenuation of the relationships between CTS and some biomechanical and work psychosocial exposures was observed after adjusting for confounding, the magnitudes were small and confirmed biomechanical and work psychosocial exposures as independent risk factors for incident CTS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

PubMed

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

2016-04-01

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

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

PubMed

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

2018-04-02

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

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

PubMed

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

2017-07-01

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

Albumin, a marker for post-operative myocardial damage in cardiac surgery.

PubMed

van Beek, Dianne E C; van der Horst, Iwan C C; de Geus, A Fred; Mariani, Massimo A; Scheeren, Thomas W L

2018-06-06

Low serum albumin (SA) is a prognostic factor for poor outcome after cardiac surgery. The aim of this study was to estimate the association between pre-operative SA, early post-operative SA and postoperative myocardial injury. This single center cohort study included adult patients undergoing cardiac surgery during 4 consecutive years. Postoperative myocardial damage was defined by calculating the area under the curve (AUC) of troponin (Tn) values during the first 72 h after surgery and its association with SA analyzed using linear regression and with multivariable linear regression to account for patient related and procedural confounders. The association between SA and the secondary outcomes (peri-operative myocardial infarction [PMI], requiring ventilation >24 h, rhythm disturbances, 30-day mortality) was studied using (multivariable) log binomial regression analysis. In total 2757 patients were included. The mean pre-operative SA was 29 ± 13 g/l and the mean post-operative SA was 26 ± 6 g/l. Post-operative SA levels (on average 26 min after surgery) were inversely associated with postoperative myocardial damage in both univariable analysis (regression coefficient - 0.019, 95%CI -0.022/-0.015, p < 0.005) and after adjustment for patient related and surgical confounders (regression coefficient - 0.014 [95% CI -0.020/-0.008], p < 0.0005). Post-operative albumin levels were significantly correlated with the amount of postoperative myocardial damage in patients undergoing cardiac surgery independent of typical confounders. Copyright © 2018. Published by Elsevier Inc.

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

PubMed

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

2016-06-20

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

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

PubMed

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

2015-05-01

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

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

PubMed

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

2017-06-23

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

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

PubMed

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

2017-12-01

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

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

PubMed Central

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

2015-01-01

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

Correlation between serum 25(OH)D values and lupus disease activity: an original article and a systematic review with meta-analysis focusing on serum VitD confounders.

PubMed

Sahebari, M; Nabavi, N; Salehi, M

2014-10-01

Notwithstanding that several original studies and some systematic reviews have been undertaken on the subject "correlation between serum values of vitamin D (VitD) and lupus disease activity," there is still no consensus on the importance of sectional measurement of serum VitD in the prediction of disease activity and important confounders in estimation of serum VitD. Medline, Web of Knowledge, and Scopus databases were searched from 1995 to 2013. The following medical subject heading (MeSH) terms and/or text words were used: "Vitamin D" OR "25OHD" OR "25(OH)D" combined with "systemic lupus erythematosus" OR "lupus" OR "SLE." References cited in the identified articles were also manually searched. Human studies in any language were included. Original research on this topic was also carried out on 82 lupus patients, considering important VitD confounders according to our systematic review and we included them in the meta-analysis. A total of 35 studies were registered for this study. Only 11 of these pointed to this correlation by Pearson test. The pooled Pearson correlation (r) of associations between disease activity and VitD was -0.365 (95% CI: -0.536, -0.165) with significant heterogeneity (p = 0.001 I (2 )= 93%). Sensitivity analysis resulted in no significant differences. The most important adjustable confounders considered by researchers were drugs, especially hydroxychloroquine, prednisolone and supplementary VitD, body mass index (BMI) and proteinuria or renal function. Only proteinuria was reported to influence VitD concentration strongly. BMI was another probable influencing factor. Our original research presented no correlation between VitD and SLEDAI (p = 0.68, r s = 0.003). This meta-analysis demonstrated that most of the studies on the relationship between VitD and lupus disease activity that found no correlation did not present the details of the statistics. However, analyzing 11 studies, most of which found a reverse correlation and reported it in detail, and our study found a weak reverse correlation between those two items. Systematic review of confounders showed that BMI, medications and kidney involvement were the most remarkable ones reported by researchers. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Impact of diurnal temperature range on human health: a systematic review.

PubMed

Cheng, Jian; Xu, Zhiwei; Zhu, Rui; Wang, Xu; Jin, Liu; Song, Jian; Su, Hong

2014-11-01

Increasing epidemiological studies have shown that a rapid temperature change within 1 day is an independent risk factor for human health. This paper aimed to systematically review the epidemiological evidence on the relationship between diurnal temperature range (DTR) and human health and to propose future research directions. A literature search was conducted in October 2013 using the databases including PubMed, ScienceDirect, and EBSCO. Empirical studies regarding the relationship between DTR and mortality and morbidity were included. Twenty-five relevant studies were identified, among which, 11 investigated the relationship between DTR and mortality and 14 examined the impact of DTR on morbidity. The majority of existing studies reported that DTR was significantly associated with mortality and morbidity, particularly for cardiovascular and respiratory diseases. Notably, compared with adults, the elderly and children were more vulnerable to DTR effects. However, there were some inconsistencies regarding the susceptible groups, lag time, and threshold of DTR. The impact of DTR on human health may be confounded or modified by season, socioeconomic, and educational status. Further research is needed to further confirm the adverse effects of DTR in different geographical locations; examine the effects of DTR on the health of children aged one or under; explore extreme DTR effects on human health; analyze the difference of DTR effects on human health in different locations and the modified effects of potential confounding factors; and develop detailed preventive measures against large DTR, particularly for susceptible groups.

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

PubMed

Pfister, Roland

2011-10-01

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

Male fertility: psychiatric considerations.

PubMed

Hall, Elise; Burt, Vivien K

2012-02-01

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

Selective serotonin reuptake inhibitors and intraoperative blood pressure.

PubMed

van Haelst, Ingrid M M; van Klei, Wilton A; Doodeman, Hieronymus J; Kalkman, Cor J; Egberts, Toine C G

2012-02-01

The influence of selective serotonin reuptake inhibitors (SSRIs) on blood pressure is poorly understood. We hypothesized that if SSRIs have an influence on blood pressure, this might become manifest in changes in intraoperative blood pressure. We aimed to study the association between perioperative use of SSRIs and changes in intraoperative blood pressure by measuring the occurrence of intraoperative hyper- and hypotension. We conducted a retrospective observational follow-up study among patients who underwent elective primary total hip arthroplasty. The index group included users of SSRIs. The reference group included a random sample (ratio 1:3) of nonusers of an antidepressant agent. The outcome was the occurrence of intraoperative hypo- and hypertensive episodes (number, mean and total duration, and area under the curve (AUC)). The outcome was adjusted for confounding factors using regression techniques. The index group included 20 users of an SSRI. The reference group included 60 nonusers. Users of SSRIs showed fewer intraoperative hypotensive episodes, a shorter mean and total duration, and a smaller AUC when compared to the reference group. After adjustment for confounders, SSRI use was associated with a significantly shorter total duration of hypotension: mean difference of -29.4 min (95% confidence interval (CI) -50.4 to -8.3). Two users of an SSRI and two patients in the reference group had a hypertensive episode. Continuation of treatment with SSRIs before surgery was associated with a briefer duration of intraoperative hypotension.

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

PubMed

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

2014-08-01

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

Psychosocial Working Conditions and Cognitive Complaints among Swedish Employees

PubMed Central

Stenfors, Cecilia U. D.; Magnusson Hanson, Linda; Oxenstierna, Gabriel; Theorell, Töres; Nilsson, Lars-Göran

2013-01-01

Background Cognitive complaints involving problems with concentration, memory, decision-making and thinking are relatively common in the work force. The sensitivity of both subjective and objective cognitive functioning to common psychiatric conditions, stress levels and to cognitive load makes it plausible that psychosocial working conditions play a role in cognitive complaints. Thus, this study aimed to test the associations between psychosocial work factors and cognitive complaints in nationally representative samples of the Swedish work force. Cross-sectional (n = 9751) and prospective (n = 3644; two time points two years apart) sequential multiple regression analyses were run, adjusting for general confounders, depressive- and sleeping problems. Additional prospective analyses were run adjusting for baseline cognitive complaints. Cross-sectional results High quantitative demands, information and communication technology (ICT) demands, underqualification and conflicts were positively associated with cognitive complaints, while social support, good resources at work and overqualification were negatively associated with cognitive complaints in all models. Skill discretion and decision authority were weakly associated with cognitive complaints. Conflicts were more strongly associated with cognitive complaints in women than in men, after adjustment for general confounders. Prospective results Quantitative job demands, ICT demands and underqualification were positively associated with future cognitive complaints in all models, including when adjusted for baseline cognitive complaints. Decision authority was weakly positively associated with future cognitive complaints, only after adjustment for depressive- and sleeping problems respectively. Social support was negatively associated with future cognitive complaints after adjustment for general confounders and baseline cognitive complaints. Skill discretion and resources were negatively associated with future cognitive complaints after adjustment for general confounders. The associations between quantitative demands and future cognitive complaints were stronger in women. Discussion/Conclusions The findings indicate that psychosocial working conditions should be taken into account when considering cognitive complaints among employees. PMID:23560101

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

PubMed

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

2017-12-01

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

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

PubMed

Tsutsumi, Chiyo; Kakuma, Tatsuyuki

2015-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

PubMed Central

Hein, David W.

2009-01-01

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

Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age

PubMed Central

Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

2015-01-01

The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4–6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45–15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence—third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration—a surrogate marker for MID—was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10–15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children. PMID:26540070

Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age.

PubMed

Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

2015-11-02

The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4-6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45-15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence-third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration-a surrogate marker for MID-was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10-15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children.

Association of Major Dietary Patterns with General and Abdominal Obesity in Iranian Patients with Type 2 Diabetes Mellitus.

PubMed

Ghane Basiri, Marjan; Sotoudeh, Gity; Djalali, Mahmood; Reza Eshraghian, Mohammad; Noorshahi, Neda; Rafiee, Masoumeh; Nikbazm, Ronak; Karimi, Zeinab; Koohdani, Fariba

2015-01-01

The aim of this study was to identify dietary patterns associated with general and abdominal obesity in type 2 diabetic patients. We included 728 patients (35 - 65 years) with type 2 diabetes mellitus in this cross-sectional study. The usual dietary intake of individuals over 1 year was collected using a validated semi-quantitative food frequency questionnaire. Weight, height, and waist circumference were measured according to standard protocol. The two major dietary patterns identified by factor analysis were healthy and unhealthy dietary patterns. After adjustment for potential confounders, subjects in the highest quintile of the healthy dietary pattern scores had a lower odds ratio for the general obesity when compared to the lowest quintile (OR = 0.45, 95 % CI = 0.26 - 0.79, P for trend = 0.02), while patients in the highest quintile of the unhealthy dietary pattern scores had greater odds for the general obesity (OR = 3.2, 95 % CI = 1.8 - 5.9, P for trend < 0.001). There were no significant associations between major dietary patterns and abdominal obesity, even after adjusting for confounding factors. This study shows that in patients with type 2 diabetes mellitus, a healthy dietary pattern is inversely associated and an unhealthy dietary pattern is directly associated with general obesity.

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

PubMed

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

2017-08-28

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

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

PubMed Central

Micek, Agnieszka; Marranzano, Marina; Ray, Sumantra

2017-01-01

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

Factors confounding impedance catheter volume measurements in vitro.

PubMed

Bielefeld, M R; Cabreriza, S E; Spotnitz, H M

1993-06-01

The impedance catheter allows continuous measurement of ventricular volume. External influences have been described as causing parallel shifts in impedance-measured volumes; however, factors affecting impedance measurements in a nonparallel manner have not been fully characterized. Accordingly, an impedance catheter was placed inside a latex balloon into which known volumes of normal saline solution were injected. Conductive and nonconductive materials were individually placed within the balloon. Impedance was measured with materials touching (T) or not touching (NT) the catheter. Impedance-measured volumes were plotted versus actual volumes. Compared with the line of identity (LID), a statistical difference (p < 0.05) was found in the slopes in the presence of metallic objects only. These included a pacing lead (T, NT) (mT = 1.32m mNT = 1.29 versus mLID = 1.00), titanium (T) (mT = 1.68 versus mLID = 1.00), and aluminum (NT) (mNT = 0.72 versus mLID = 1.00). These changes in slope indicate nonparallel effects on impedance that confound the ability of the impedance catheter to determine volumes in vitro. These observations imply that serial calibration of both the slope constant (alpha) and the intercept (parallel conductance) of impedance may be necessary for in vivo measurements of ventricular volume based on impedance in the presence of metallic objects.

Learning fast accurate movements requires intact frontostriatal circuits

PubMed Central

Shabbott, Britne; Ravindran, Roshni; Schumacher, Joseph W.; Wasserman, Paula B.; Marder, Karen S.; Mazzoni, Pietro

2013-01-01

The basal ganglia are known to play a crucial role in movement execution, but their importance for motor skill learning remains unclear. Obstacles to our understanding include the lack of a universally accepted definition of motor skill learning (definition confound), and difficulties in distinguishing learning deficits from execution impairments (performance confound). We studied how healthy subjects and subjects with a basal ganglia disorder learn fast accurate reaching movements. We addressed the definition and performance confounds by: (1) focusing on an operationally defined core element of motor skill learning (speed-accuracy learning), and (2) using normal variation in initial performance to separate movement execution impairment from motor learning abnormalities. We measured motor skill learning as performance improvement in a reaching task with a speed-accuracy trade-off. We compared the performance of subjects with Huntington's disease (HD), a neurodegenerative basal ganglia disorder, to that of premanifest carriers of the HD mutation and of control subjects. The initial movements of HD subjects were less skilled (slower and/or less accurate) than those of control subjects. To factor out these differences in initial execution, we modeled the relationship between learning and baseline performance in control subjects. Subjects with HD exhibited a clear learning impairment that was not explained by differences in initial performance. These results support a role for the basal ganglia in both movement execution and motor skill learning. PMID:24312037

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

PubMed

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

2018-06-01

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

Disruptive behaviour disorders: a systematic review of environmental antenatal and early years risk factors.

PubMed

Latimer, K; Wilson, P; Kemp, J; Thompson, L; Sim, F; Gillberg, C; Puckering, C; Minnis, H

2012-09-01

Disruptive behaviour disorders (DBDs), including attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD) are chronic disorders with significant overlap in aetiology and presentation. An integrative examination of environmental risk factors is lacking. Six literature searches of web-based bibliographic databases were completed to identify literature on DBDs in general and five disorders in particular: CD, ODD, ADHD, deficits of attention, motor control and perception, and reactive attachment disorder. Searches were filtered to focus on studies including diagnostic assessment, focussing on environmental risk and protective factors in the first 4 years of life. The database searches generated 9806 papers of which 47 were reviewed after filters had been applied. The evidence suggests links between a number of early life risk factors and DBDs, including prenatal cigarette smoking and alcohol use, prenatal viral illness, maternal stress and anxiety, low birthweight, peri-partum and early neonatal complications, parental stress and parenting styles in infancy, early deprivation, adoption and separation. Despite the understanding that there is sharing of risk factors between the DBDs, there has been a disproportionate focus on the role of certain risk factors at the expense of others and the field is weakened by difficulties in controlling for all potential confounding variables. © 2012 Blackwell Publishing Ltd.

Five Steps to Successfully Implement and Evaluate Propensity Score Matching in Clinical Research Studies.

PubMed

Staffa, Steven J; Zurakowski, David

2018-01-09

In clinical research, the gold standard level of evidence is the randomized controlled trial (RCT). The availability of nonrandomized retrospective data is growing; however, a primary concern of analyzing such data is comparability of the treatment groups with respect to confounding variables. Propensity score matching (PSM) aims to equate treatment groups with respect to measured baseline covariates to achieve a comparison with reduced selection bias. It is a valuable statistical methodology that mimics the RCT, and it may create an "apples to apples" comparison while reducing bias due to confounding. PSM can improve the quality of anesthesia research and broaden the range of research opportunities. PSM is not necessarily a magic bullet for poor-quality data, but rather may allow the researcher to achieve balanced treatment groups similar to a RCT when high-quality observational data are available. PSM may be more appealing than the common approach of including confounders in a regression model because it allows for a more intuitive analysis of a treatment effect between 2 comparable groups.We present 5 steps that anesthesiologists can use to successfully implement PSM in their research with an example from the 2015 Pediatric National Surgical Quality Improvement Program: a validated, annually updated surgery and anesthesia pediatric database. The first step of PSM is to identify its feasibility with regard to the data at hand and ensure availability of data on any potential confounders. The second step is to obtain the set of propensity scores from a logistic regression model with treatment group as the outcome and the balancing factors as predictors. The third step is to match patients in the 2 treatment groups with similar propensity scores, balancing all factors. The fourth step is to assess the success of the matching with balance diagnostics, graphically or analytically. The fifth step is to apply appropriate statistical methodology using the propensity-matched data to compare outcomes among treatment groups.PSM is becoming an increasingly more popular statistical methodology in medical research. It often allows for improved evaluation of a treatment effect that may otherwise be invalid due to a lack of balance between the 2 treatment groups with regard to confounding variables. PSM may increase the level of evidence of a study and in turn increases the strength and generalizability of its results. Our step-by-step approach provides a useful strategy for anesthesiologists to implement PSM in their future research.

Headache cessation by an educational intervention in grammar schools: a cluster randomized trial.

PubMed

Albers, L; Heinen, F; Landgraf, M; Straube, A; Blum, B; Filippopulos, F; Lehmann, S; Mansmann, U; Berger, U; Akboga, Y; von Kries, R

2015-02-01

Headache is a common health problem in adolescents. There are a number of risk factors for headache in adolescents that are amenable to intervention. The aim of the study was to assess the effectiveness of a low-level headache prevention programme in the classroom setting to prevent these risk factors. In all, 1674 students in 8th-10th grade at 12 grammar schools in greater Munich, Germany, were cluster randomized into intervention and control groups. A standardized 60-min prevention lesson focusing on preventable risk factors for headache (physical inactivity, coffee consumption, alcohol consumption and smoking) and providing instructions on stress management and neck and shoulder muscle relaxation exercises was given in a classroom setting. Seven months later, students were reassessed. The main outcome parameter was headache cessation. Logistic regression models with random effects for cluster and adjustment for baseline risk factors were calculated. Nine hundred students (intervention group N = 450, control group N = 450) with headache at baseline and complete data for headache and confounders were included in the analysis. Headache cessation was observed in 9.78% of the control group compared with 16.22% in the intervention group (number needed to treat = 16). Accounting for cluster effects and confounders, the probability of headache cessation in the intervention group was 1.77 (95% confidence interval = [1.08; 2.90]) higher than in the control group. The effect was most pronounced in adolescents with tension-type headache: odds ratio = 2.11 (95% confidence interval = [1.15; 3.80]). Our study demonstrates the effectiveness of a one-time, classroom-based headache prevention programme. © 2014 EAN.

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

PubMed Central

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2014-06-01

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

Association between obesity and chronic periodontitis: a cross-sectional study.

PubMed

Palle, Ajay Reddy; Reddy, C M Sanjeeva Kumar; Shankar, B Shiva; Gelli, Vemsi; Sudhakar, Jaradoddi; Reddy, K Krishna Mohana

2013-03-01

Chronic periodontitis is multifactorial and numerous risk factors have been identified to contribute in the disease progression. Current study aimed to conduct a cross-sectional study in a population of patients with cardiovascular diseases in order to correlate the association between obesity [body mass index (BMI) and waist circumference (WC)] and periodontal disease parameters. The study was of a cross-sectional design and a total of 201 patients were examined after obtaining their informed consent. Subjects who had a history of cardiovascular diseases and under treatment were included in the study. Two indicators of obesity were used: BMI and WC. The following periodontal parameters were assessed: Probing depth, clinical attachment level. The oral hygiene status of the subjects was assessed by the oral hygiene index (OHI, simplified) given by John C Greene and Jack R Vermillion. The influence of the BMI and other confounding variables on periodontitis severity was assessed by multivariate logistic regression analysis. Data were analyzed using SPSS. Significant association was seen with low density lipoproteins (LDL) and severity of periodontitis (p < 0.005), triglyceride levels (TGL) and severity of periodontitis (p < 0.005), cholesterol and severity of periodontitis (p < 0.005), BMI and severity of periodontitis (p < 0.001), OHI and severity of periodontitis (p < 0.001). Significant association was seen with smoking and severity of periodontitis (p < 0.005), BMI and severity of periodontitis (p < 0.001), WC and severity of periodontitis (p < 0.001), cholesterol and severity of periodontitis (p < 0.001), OHI and severity of periodontitis (p < 0.001). Obesity has been implicated as a risk factor for several conditions including cardiovascular disease, diabetes, etc. In our study the relation between measures of overall and abdominal obesity (BMI and WC) and periodontal disease showed significant association in the multivariate logistic regression analysis independent of other confounding factors. Obesity can act as a significant risk factor in progression of periodontitis.

Type D personality is associated with increased metabolic syndrome prevalence and an unhealthy lifestyle in a cross-sectional Dutch community sample.

PubMed

Mommersteeg, Paula M C; Kupper, Nina; Denollet, Johan

2010-11-19

People with Type D-Distressed-personality have a general tendency towards increased negative affectivity (NA), while at the same time inhibiting these emotions in social situations (SI). Type D personality is associated with an increased risk of adverse outcomes in patients with cardiovascular disease. Whether Type D personality is a cardiovascular risk factor in healthy populations remains to be investigated. In the present study, the relations between Type D personality and classical cardiovascular risk factors, i.e. metabolic syndrome and lifestyle were investigated in a Dutch community sample. In a cross-sectional study 1592 participants were included, aged 20-80 years. Metabolic syndrome was defined by self-report, following the International Diabetes Federation-IDF-guidelines including an increased waist circumference, dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking, alcohol use, exercise and dietary habits were examined. Metabolic syndrome prevalence was stratified by Type D personality (a high score on both NA and SI), lifestyle and confounders age, gender, having a partner, higher education level, cardiac history, family history of cardiovascular disease. Metabolic syndrome was more prevalent in persons with a Type D personality (13% vs. 6%). Persons with Type D personality made poorer lifestyle choices, adhered less to the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, p = .02), had a less varied diet (OR = 0.50, 95%CI = 0.40-0.70, p < .0005), and were less likely to restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, p = .01). Type D personality was related to a twofold increased risk of metabolic syndrome (OR = 2.2, 95%CI = 1.2-4.0, p = .011), independent of lifestyle factors and confounders. Type D personality is related to an increased prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both behavioral and biological vulnerability for development of cardiovascular disorders and diabetes.

Maternal and Paternal Height and the Risk of Preeclampsia.

PubMed

Lee, Yunsung; Magnus, Per

2018-04-01

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

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

PubMed

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

2006-12-01

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

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

PubMed

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

2017-06-15

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

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

PubMed Central

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

2017-01-01

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

Factors Influencing Cognitive Function in Subjects With COPD.

PubMed

Dag, Ersel; Bulcun, Emel; Turkel, Yakup; Ekici, Aydanur; Ekici, Mehmet

2016-08-01

The aim of this study was to assess the association between cognitive function and age, pulmonary function, comorbidity index, and the 6-min walk distance in subjects with COPD as well as to compare the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in terms of their ability to identify cognitive dysfunction in subjects with COPD. A total of 52 individuals with stable COPD were included in this study. Cognitive function was assessed using MMSE and MoCA. Age, body mass index, the Modified Cumulative Illness Rating Scale, 6-min walk distance, arterial blood gases, and pulmonary function tests were assessed and recorded. The range and SD of scores in subjects with COPD were larger with MoCA than with MMSE. MMSE and MoCA scores are associated with 6-min walk distance and comorbidity index in subjects with COPD. General cognitive function measured by MoCA was negatively correlated with the comorbidity index but was positively associated with 6-min walk distance in subjects with COPD after controlling for possible confounding factors in the multivariate model. However, general cognitive function measured by MMSE was not correlated with the comorbidity index and 6-min walk distance in subjects with COPD, after controlling for possible confounding factors in the multivariate model. MoCA may be a more reliable screening test than MMSE in detecting cognitive impairment in subjects with COPD. The addition of cognitive tests on assessment of subjects with COPD can provide further benefit. Copyright © 2016 by Daedalus Enterprises.

Influence of potentially confounding factors on sea urchin porewater toxicity tests

USGS Publications Warehouse

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

2006-01-01

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

[Teenage pregnancy and frequent use of alcohol and drugs in the home environment].

PubMed

Caputo, Valéria Garcia; Bordin, Isabel Altenfelder

2008-06-01

To assess individual and family factors associated to teenage pregnancy, including frequent use of alcohol and illicit drugs by family members. Case-control study conducted with a sample of 408 sexually active female adolescents (aged 13-17 years) in school from the city of Marília (Southeastern Brazil) in 2003-2004. Cases consisted of 100 primigravid teenagers assisted in prenatal care programs in health units. Controls were 308 nulligravid students from state public schools. Standardized instruments identified demographic and educational factors, contraceptive behavior, mental health problems, and family characteristics. Statistical analysis included chi-square tests and logistic regression models. Low paternal education (p=0.01), lack of information on sexuality and fertilization (p=0.001) and the use of illicit drugs by a resident family member (p=0.006) were independent risk factors. Family income per capita and asking the partner to use a condom were confounders. The frequent use of illicit drugs by a resident family member is a factor strongly associated to teenage pregnancy, regardless of other risk factors. The expectation of going to college constitutes a protective factor, mainly in the presence of low maternal education.

Association between socio-economic status and dental caries in elderly people in Sichuan Province, China: a cross-sectional study.

PubMed

Wang, Linyan; Cheng, Li; Yuan, Bo; Hong, Xiao; Hu, Tao

2017-09-24

As a vulnerable group, the elders' oral health gained less attention, particularly the relationship between socioeconomic status (SES) and dental caries. This study aimed to assess the associations and to explore the effects of confounders on the associations in elderly people. Cross-sectional study. 3 neighbourhood committees and 3 village committees in Sichuan Province, China. 744 people (362 men and 382 women) aged 65-74 years were included. Oral health outcomes included the decayed, missing and filled teeth (DMFT) index and its components. SES was assigned by educational level, household income and type of household. The bivariate association between the participants' characteristics and DMFT was analysed using non-parametric tests. Four logistic regression models were used to analyse the associations between SES and dental caries by regulating confounders. Poor oral health was observed in these participants. Bivariate analysis showed a significant association between SES and DMFT (p﹤0.05). Only adjusting gender, high educational level (adjusted (AOR)=0.34, 95% CI 0.17 to 0.66), high household income (AOR=0.47, 95% CI 0.41 to 0.77) were protective factors against dental caries, and living in agricultural families (AOR=1.86, 95% CI 1.32 to 2.63) was risk factor (p﹤0.05). After adjusting other confounders, SES was partly related to the dental caries. Moreover, an interaction existed among SES indicators. SES is associated with dental caries, and older people with low SES have poor oral health. The associations were explained partly by diet, behaviour and awareness. Our results provide effective evidence in targeted policy-making and intervention measures and implicate that pertinence measures, economic assistance and medical insurance funds should be provided to older people of low SES. Furthermore, a follow-up design should attempt to confirm the causal relationship between SES and dental caries and evaluate the effect of intervention. © 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.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-01-01

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

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

DTIC Science & Technology

1999-10-01

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

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

PubMed

Raigrodski, Ariel J; Dogan, Sami

2008-05-01

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

Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up.

PubMed

Piirtola, Maarit; Kaprio, Jaakko; Kujala, Urho M; Heikkilä, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Ropponen, Annina

2016-08-04

Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day) was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models. Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations. Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow-up. The association was found after adjusting for several confounders, including familial factors. Hence, the results point to the conclusion that education has an independent role in the development of long-term physical inactivity and tailored efforts to promote physical activity among lower educated people would be needed throughout adulthood.

The link between discrimination and telomere length in African American adults.

PubMed

Lee, Daniel B; Kim, Eric S; Neblett, Enrique W

2017-05-01

Prior work shows that discrimination is associated with a wide array of negative health outcomes. However, the biological mechanisms through which this link occurs require more study. We evaluated the association between discrimination and leukocyte telomere length (LTL; a biological marker of systemic aging). Cross-sectional data were from the Health and Retirement study, a study of people aged 51+ in the United States, and included 595 African American males and females. Multiple regression analyses were used to evaluate whether discrimination was independently associated with LTL. We also considered the role of potential confounders including sociodemographic factors, health factors, depressive symptoms, and stress. High discrimination was associated with shorter LTL after controlling for sociodemographic factors (b = -.034, SE = 0.14, p = .017). This association persisted in analyses that further adjusted for health factors, depressive symptoms, and stress. Results suggest that discrimination experiences accelerate biological aging in older African American males and females, alike. This finding helps advance our understanding of how discrimination generates greater disease vulnerability and premature death in African Americans. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed

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

2014-10-01

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

Mismeasurement and the resonance of strong confounders: uncorrelated errors.

PubMed

Marshall, J R; Hastrup, J L

1996-05-15

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

Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design.

PubMed

Laukens, Debby; Brinkman, Brigitta M; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

2016-01-01

Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host-microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. © FEMS 2015.

Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design

PubMed Central

Laukens, Debby; Brinkman, Brigitta M.; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

2015-01-01

Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host–microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. PMID:26323480

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

PubMed

Clark, Sarah; Farrington, Ken; Chilcot, Joseph

2014-01-01

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

Genetic Instrumental Variable Studies of Effects of Prenatal Risk Factors

PubMed Central

von Hinke Kessler Scholder, Stephanie

2013-01-01

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

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

PubMed

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

2013-06-01

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

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

PubMed

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

2007-09-01

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

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

PubMed

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

2014-01-01

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

Lung cancer and diesel exhaust: an updated critical review of the occupational epidemiology literature

PubMed Central

Gamble, John F.; Nicolich, Mark J.; Boffetta, Paolo

2012-01-01

A recent review concluded that the evidence from epidemiology studies was indeterminate and that additional studies were required to support the diesel exhaust-lung cancer hypothesis. This updated review includes seven recent studies. Two population-based studies concluded that significant exposure-response (E-R) trends between cumulative diesel exhaust and lung cancer were unlikely to be entirely explained by bias or confounding. Those studies have quality data on life-style risk factors, but do not allow definitive conclusions because of inconsistent E-R trends, qualitative exposure estimates and exposure misclassification (insufficient latency based on job title), and selection bias from low participation rates. Non-definitive results are consistent with the larger body of population studies. An NCI/NIOSH cohort mortality and nested case-control study of non-metal miners have some surrogate-based quantitative diesel exposure estimates (including highest exposure measured as respirable elemental carbon (REC) in the workplace) and smoking histories. The authors concluded that diesel exhaust may cause lung cancer. Nonetheless, the results are non-definitive because the conclusions are based on E-R patterns where high exposures were deleted to achieve significant results, where a posteriori adjustments were made to augment results, and where inappropriate adjustments were made for the “negative confounding” effects of smoking even though current smoking was not associated with diesel exposure and therefore could not be a confounder. Three cohort studies of bus drivers and truck drivers are in effect air pollution studies without estimates of diesel exhaust exposure and so are not sufficient for assessing the lung cancer-diesel exhaust hypothesis. Results from all occupational cohort studies with quantitative estimates of exposure have limitations, including weak and inconsistent E-R associations that could be explained by bias, confounding or chance, exposure misclassification, and often inadequate latency. In sum, the weight of evidence is considered inadequate to confirm the diesel-lung cancer hypothesis. PMID:22656672

Environmental risk factors associated with bovine tuberculosis among cattle in high-risk areas

PubMed Central

Winkler, B.; Mathews, F.

2015-01-01

Our research shows that environmental features are important predictors of bovine tuberculosis (bTB) in British cattle herds in high-prevalence regions. Data from 503 case and 808 control farms included in the randomized badger culling trial (RBCT) were analysed. bTB risk increased in larger herds and on farms with greater areas of maize, deciduous woodland and marsh, whereas a higher percentage of boundaries composed of hedgerows decreased the risk. The model was tested on another case–control study outside RBCT areas, and here it had a much smaller predictive power. This suggests that different infection dynamics operate outside high-risk areas, although it is possible that unknown confounding factors may also have played a role. PMID:26559511

Maternal smoking during pregnancy and child outcomes: Real or spurious effect?

PubMed Central

Knopik, Valerie S.

2013-01-01

Maternal smoking during pregnancy (MSDP) is a major public health concern with clearly established consequences to both mother and newborn (e.g., low birth weight, altered cardiorespiratory responses). MSDP has also been associated with higher rates of a variety of poor cognitive and behavioral outcomes in children, including ADHD, conduct disorder, impaired learning and memory, and cognitive dysfunction. However, the evidence suggesting causal effects of MSDP for these outcomes is muddied in the existing literature due to the frequent inability to separate prenatal exposure effects from other confounding environmental and genetic factors. Carefully designed studies using genetically sensitive strategies can build upon current evidence and begin to elucidate the likely complex factors contributing to associations between MSDP and child outcomes. PMID:19142764

Mismatch of Posttraumatic Stress Disorder (PTSD) Symptoms and DSM-IV Symptom Clusters in a Cancer Sample: Exploratory Factor Analysis of the PTSD Checklist-Civilian Version

PubMed Central

Shelby, Rebecca A.; Golden-Kreutz, Deanna M.; Andersen, Barbara L.

2007-01-01

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994a) conceptualization of posttraumatic stress disorder (PTSD) includes three symptom clusters: reexperiencing, avoidance/numbing, and arousal. The PTSD Checklist-Civilian Version (PCL-C) corresponds to the DSM-IV PTSD symptoms. In the current study, we conducted exploratory factor analysis (EFA) of the PCL-C with two aims: (a) to examine whether the PCL-C evidenced the three-factor solution implied by the DSM-IV symptom clusters, and (b) to identify a factor solution for the PCL-C in a cancer sample. Women (N = 148) with Stage II or III breast cancer completed the PCL-C after completion of cancer treatment. We extracted two-, three-, four-, and five-factor solutions using EFA. Our data did not support the DSM-IV PTSD symptom clusters. Instead, EFA identified a four-factor solution including reexperiencing, avoidance, numbing, and arousal factors. Four symptom items, which may be confounded with illness and cancer treatment-related symptoms, exhibited poor factor loadings. Using these symptom items in cancer samples may lead to overdiagnosis of PTSD and inflated rates of PTSD symptoms. PMID:16281232

Antidepressant sales and regional variations of suicide mortality in Germany.

PubMed

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.

Mental disorders and vulnerability to homicidal death: Swedish nationwide cohort study.

PubMed

Crump, Casey; Sundquist, Kristina; Winkleby, Marilyn A; Sundquist, Jan

2013-03-04

To determine the risk of people with mental disorders being victims of homicide. National cohort study. Sweden. Entire adult population (n = 7,253,516). Homicidal death during eight years of follow-up (2001-08); hazard ratios for the association between mental disorders and homicidal death, with adjustment for sociodemographic confounders; potential modifying effect of comorbid substance use. 615 homicidal deaths occurred in 54.4 million person years of follow-up. Mortality rates due to homicide (per 100,000 person years) were 2.8 among people with mental disorders compared with 1.1 in the general population. After adjustment for sociodemographic confounders, any mental disorder was associated with a 4.9-fold (95% confidence interval 4.0 to 6.0) risk of homicidal death, relative to people without mental disorders. Strong associations were found irrespective of age, sex, or other sociodemographic characteristics. Although the risk of homicidal death was highest among people with substance use disorders (approximately ninefold), the risk was also increased among those with personality disorders (3.2-fold), depression (2.6-fold), anxiety disorders (2.2-fold), or schizophrenia (1.8-fold) and did not seem to be explained by comorbid substance use. Sociodemographic risk factors included male sex, being unmarried, and low socioeconomic status. In this large cohort study, people with mental disorders, including those with substance use disorders, personality disorders, depression, anxiety disorders, or schizophrenia, had greatly increased risks of homicidal death. Interventions to reduce violent death among people with mental disorders should tackle victimisation and homicidal death in addition to suicide and accidents, which share common risk factors.

Association Between National Board Dental Examination Part II Scores and Comprehensive Examinations at Harvard School of Dental Medicine.

PubMed

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.

Tobacco smoking is associated with psychotic experiences in the general population of South London.

PubMed

Bhavsar, V; Jauhar, S; Murray, R M; Hotopf, M; Hatch, S L; McNeill, A; Boydell, J; MacCabe, J H

2018-01-01

The association between cigarette smoking and psychosis remains unexplained, but could relate to causal effects in both directions, confounding by socioeconomic factors, such as ethnicity, or use of other substances, including cannabis. Few studies have evaluated the association between cigarettes and psychotic experiences (PEs) in diverse, inner-city populations, or relationships with number of cigarettes consumed. We assessed associations and dose-response relationships between cigarette smoking and PEs in a cross-sectional survey of household residents (n = 1680) in South East London, using logistic regression to adjust for cannabis use, other illicit substances, and socioeconomic factors, including ethnicity. We found association between any PEs and daily cigarette smoking, which remained following adjustment for age, gender, ethnicity, cannabis and use of illicit stimulant drugs (fully adjusted odds ratio 1.47, 95% confidence interval 1.01-2.15). Fully adjusted estimates for the association, and with number of PEs, increased with number of cigarettes smoked daily, implying a dose-response effect (p = 0.001 and <0.001, respectively). Odds of reporting any PEs in ex-smokers were similar to never-smokers. In this diverse epidemiological sample, association between smoking and PEs was not explained by confounders such as cannabis or illicit drugs. Daily cigarette consumption showed a dose-response relationship with the odds of reporting PEs, and of reporting a greater number of PEs. There was no difference in odds of reporting PEs between ex-smokers and never-smokers, raising the possibility that the increase in PEs associated with smoking may be reversible.

Occupational Stress and Physical Symptoms among Family Medicine Residents

PubMed Central

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

2013-01-01

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

Drosophila melanogaster as a model system for the evaluation of anti-aging compounds.

PubMed

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.

Epidemiological research on radiation-induced cancer in atomic bomb survivors

PubMed Central

Ozasa, Kotaro

2016-01-01

The late effects of exposure to atomic bomb radiation on cancer occurrence have been evaluated by epidemiological studies on three cohorts: a cohort of atomic bomb survivors (Life Span Study; LSS), survivors exposed in utero, and children of atomic bomb survivors (F1). The risk of leukemia among the survivors increased remarkably in the early period after the bombings, especially among children. Increased risks of solid cancers have been evident since around 10 years after the bombings and are still present today. The LSS has clarified the dose–response relationships of radiation exposure and risk of various cancers, taking into account important risk modifiers such as sex, age at exposure, and attained age. Confounding by conventional risk factors including lifestyle differences is not considered substantial because people were non-selectively exposed to the atomic bomb radiation. Uncertainty in risk estimates at low-dose levels is thought to be derived from various sources, including different estimates of risk at background levels, uncertainty in dose estimates, residual confounding and interaction, strong risk factors, and exposure to residual radiation and/or medical radiation. The risk of cancer in subjects exposed in utero is similar to that in LSS subjects who were exposed in childhood. Regarding hereditary effects of radiation exposure, no increased risk of cancers associated with parental exposure to radiation have been observed in the F1 cohort to date. In addition to biological and pathogenetic interpretations of the present results, epidemiological investigations using advanced technology should be used to further analyze these cohorts. PMID:26976124

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

PubMed

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

2017-11-01

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

Does length or neighborhood size cause the word length effect?

PubMed

Jalbert, Annie; Neath, Ian; Surprenant, Aimée M

2011-10-01

Jalbert, Neath, Bireta, and Surprenant (2011) suggested that past demonstrations of the word length effect, the finding that words with fewer syllables are recalled better than words with more syllables, included a confound: The short words had more orthographic neighbors than the long words. The experiments reported here test two predictions that would follow if neighborhood size is a more important factor than word length. In Experiment 1, we found that concurrent articulation removed the effect of neighborhood size, just as it removes the effect of word length. Experiment 2 demonstrated that this pattern is also found with nonwords. For Experiment 3, we factorially manipulated length and neighborhood size, and found only effects of the latter. These results are problematic for any theory of memory that includes decay offset by rehearsal, but they are consistent with accounts that include a redintegrative stage that is susceptible to disruption by noise. The results also confirm the importance of lexical and linguistic factors on memory tasks thought to tap short-term memory.

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

PubMed

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

2012-04-01

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

Maternal obesity and childhood wheezing and asthma.

PubMed

Rusconi, Franca; Popovic, Maja

2017-03-01

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

Factors Influencing Observed Tillage Impacts on Herbicide Transport

USDA-ARS?s Scientific Manuscript database

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

Effect of maternal and neonatal factors on neonatal thyroid stimulating hormone: Results from a population-based prospective cohort study in China.

PubMed

Zhang, Yixin; Du, Cong; Wang, Wei; Chen, Wen; Shao, Ping; Wang, Chongdan; Leng, Junhong; Shen, Jun; Tan, Long; Zhang, Wanqi

2018-09-01

Neonatal TSH screening is effective in detecting congenital hypothyroidism and estimating iodine status in a given population, but various factors influence TSH levels. The aim of this study was to evaluate the effect of maternal and neonatal factors on neonatal TSH levels. Data were obtained from an ongoing prospective cohort study. A total of 988 pregnant women and their newborn infants participated in the study from April 2015 to May 2017 at Tianjin Maternal and Child Health Center and Tanggu Maternity Hospital in Tianjin, China. Maternal demographic information, including age, height, and parity, was recorded by questionnaire. Fasting blood and urinary samples were collected from all pregnant women. After parturition, information on gestation duration, mode of delivery, neonatal sex, neonatal TSH, neonatal birth weight, and neonatal birth height were recorded. Maternal age, maternal BMI, gestation duration, parity, and neonatal birth weight and height were significantly correlated with neonatal TSH (p < 0.05). Quantile regression revealed that maternal age, TSH, FT 4 , and gestation duration were positively correlated with neonatal TSH level. A logistic regression model identified maternal BMI, TSH, and birth height as risk factors for having neonatal TSH > 5 mIU/L (p < 0.05). Neonatal TSH levels are dynamic and may be affected by several maternal and neonatal factors including maternal age, TSH, FT 4 , and birth weight and height. Identification of these confounders is useful for assessing the status of neonatal thyroid development. STRENGTHS AND LIMITATIONS OF THIS STUDY: (1) Iodine deficiency disorder has generally been eliminated, so the median urinary iodine concentration of pregnancy is higher than 150 μg/L even in mildly or moderately iodine deficient areas. (2) Unlike many other studies, which did not consider the complexity of factors or examined only one or two variables, this study used a multivariate model to analyze the data. (3) This study examined numerous high-risk factors in pregnant women and considered the biological interrelation between them. Future studies should consider these confounding factors for neonatal TSH levels and establish a proper neonatal TSH range for monitoring the iodine status of a population or diagnosing congenital hypothyroidism. Copyright © 2018 Elsevier GmbH. All rights reserved.

The field performance of frontal air bags: a review of the literature.

PubMed

Kent, Richard; Viano, David C; Crandall, Jeff

2005-03-01

This article presents a broad review of the literature on frontal air bag field performance, starting with the initial government and industry projections of effectiveness and concluding with the most recent assessments of depowered systems. This review includes as many relevant metrics as practicable, interprets the findings, and provides references so the interested reader can further evaluate the limitations, confounders, and utility of each metric. The evaluations presented here range from the very specific (individual case studies) to the general (statistical analyses of large databases). The metrics used to evaluate air bag performance include fatality reduction or increase; serious, moderate, and minor injury reduction or increase; harm reduction or increase; and cost analyses, including insurance costs and the cost of life years saved for various air bag systems and design philosophies. The review begins with the benefits of air bags. Fatality and injury reductions attributable to the air bag are presented. Next, the negative consequences of air bag deployment are described. Injuries to adults and children and the current trends in air bag injury rates are discussed, as are the few documented instances of inadvertent deployments or non-deployment in severe crashes. In the third section, an attempt is made to quantify the influence of the many confounding factors that affect air bag performance. The negative and positive characteristics of air bags are then put into perspective within the context of societal costs and benefits. Finally, some special topics, including risk homeostasis and the performance of face bags, are discussed.

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

USGS Publications Warehouse

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

2009-01-01

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

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

USGS Publications Warehouse

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

2009-01-01

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

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

PubMed Central

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

2008-01-01

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

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

PubMed Central

McLaws, Mary-Louise

2015-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2018-05-16

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

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

PubMed

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

2018-05-03

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

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-06-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-22

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

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

PubMed

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

1998-07-01

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

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

PubMed Central

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

1996-01-01

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

Association between metabolic syndrome and bone fracture risk: A community-based study using a fracture risk assessment tool.

PubMed

Yu, Chia-Ying; Chen, Fang-Ping; Chen, Li-Wei; Kuo, Sheng-Fong; Chien, Rong-Nan

2017-12-01

Osteoporosis and metabolic syndrome (MS) share similar risk factors. Previous studies of association between bone marrow density (BMD) and MS are controversial. Moreover, some studies revealed that MS is associated with BMD but not with bone fracture. In clinical practice, patients pay more attention to bone fracture risk than BMD values. Hence, this study aimed to evaluate the association between MS and the 10-year bone fracture risk probability using a fracture risk assessment tool (FRAX) from community-based data. From March 2014 to August 2015, 2689 participants (897 men and 1792 women) were enrolled in this study. Inflammatory cytokines, such as tumor necrosis factor alpha and C-reactive protein, and adipokines were included for analysis.The mean age was 60.2 ± 10.7 years in men and 58.9 ± 9.6 years in women. The percentage of MS was 27.6% in men and 27.9% in women. Participants were divided into 2 groups, those with or without MS. Compared with women without MS, women with MS had a higher rate of fracture risk (22.8% vs 16.3%, P = .001). In contrast, men with MS had a lower rate of fracture risk then men without MS (5.6% vs 12.3%, P = .004). However, MS loss the association with a high bone fracture risk in men based on multivariate logistical regression analysis, after adjusting for confounding factor of body mass index (BMI). Conclusively, the result of regression analysis between MS and the bone fracture risk may be different in men and women, and BMI was an important confounding factor to interfere with the regression analysis. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Risk of Autism Associated With Hyperbilirubinemia and Phototherapy.

PubMed

Wu, Yvonne W; Kuzniewicz, Michael W; Croen, Lisa; Walsh, Eileen M; McCulloch, Charles E; Newman, Thomas B

2016-10-01

Whether neonatal hyperbilirubinemia and/or phototherapy increase the risk of autism spectrum disorder (ASD) is unclear. We sought to quantify the risk of ASD associated with elevated total serum bilirubin (TSB) levels and with phototherapy. In a retrospective cohort study of 525 409 infants born at ≥35 weeks' gestation in 15 Kaiser Permanente Northern California (KPNC) hospitals, 1995-2011, we obtained all TSB levels and determined which infants received phototherapy. From the KPNC Autism Registry, we identified patients with ASD diagnosed at a KPNC Autism Center, by a clinical specialist, or by a pediatrician. We calculated Cox proportional hazard ratios (HRs) for time to diagnosis of ASD, adjusting for confounding factors. Among infants in the birth cohort, 2% had at least 1 TSB level ≥20 mg/dL, and 8% received phototherapy. The rate of ASD was 13 per 1000 births. Crude analyses revealed an association between TSB ≥20 and ASD (relative risk: 1.4; 95% confidence interval [CI]: 1.1-1.6), and between phototherapy and ASD (relative risk: 1.7; 95% CI: 1.5-1.8). After adjusting for confounders, TSB ≥20 (HR: 1.09; 95% CI: 0.89-1.35) and phototherapy (HR: 1.10; 95% CI: 0.98-1.24) were no longer significantly associated with ASD. Independent risk factors for ASD included maternal and paternal age; maternal and paternal higher education; male sex; birth weight <2500 g or ≥4200 g; and later year of birth. After adjustment for the effects of sociodemographic factors and birth weight, neither hyperbilirubinemia nor phototherapy was an independent risk factor for ASD. Copyright © 2016 by the American Academy of Pediatrics.

Towards an understanding of the relationship of functional literacy and numeracy to geographical health inequalities.

PubMed

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.

Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study.

PubMed

O'Neill, Sinéad M; Curran, Eileen A; Dalman, Christina; Kenny, Louise C; Kearney, Patricia M; Clarke, Gerard; Cryan, John F; Dinan, Timothy G; Khashan, Ali S

2016-05-01

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n= 1,345,210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ(2)for heterogeneityP= .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2011-02-01

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

Maternal Consumption of Coffee and Caffeine-containing Beverages and Oral Clefts: A Population-based Case-Control Study in Norway

PubMed Central

Wilcox, Allen J.; Lie, Rolv T.; Andersen, Lene F.; Drevon, Christian A.

2009-01-01

A large, population-based case-control study of facial clefts was carried out in Norway between 1996 and 2001. The study included 573 cases—377 with cleft lip with or without cleft palate and 196 with cleft palate only—and 763 randomly selected controls. Maternal consumption of coffee and other caffeine-containing beverages in early pregnancy was recorded shortly after birth. Compared with that for no coffee consumption, the adjusted odds ratios for cleft lip with or without cleft palate were 1.39 (95% confidence interval: 1.01, 1.92) for less than 3 cups a day and 1.59 (95% confidence interval: 1.05, 2.39) for 3 cups or more. Coffee consumption was not associated with risk of cleft palate only (for ≥3 cups vs. none, adjusted odds ratio = 0.96, 95% confidence interval: 0.55, 1.67). Tea consumption was associated with a reduced odds ratio of both cleft lip with or without cleft palate and cleft palate only. There was little evidence of an association between caffeine exposure and clefts when all sources of caffeine were considered. Adjustment for known confounding factors in general had minor effects on risk estimates. Still, the authors could not rule out the possibility of uncontrolled confounding by factors associated with the habit of drinking coffee. PMID:19342400

Plasma 17-alpha-OH-progesterone in female workers exposed to urban pollutants.

PubMed

Ciarrocca, M; Cerratti, D; Capozzella, A; Rosati, M V; Anzani, M F; Bernardini, A; Casale, T; Pimpinella, B; Tomei, G; Monti, C; Tomao, E; Tomei, F

2006-01-01

The aim of this study is to evaluate whether occupational exposure to urban pollutants could cause alteration in plasma 17-alpha-OH-P levels in female workers. After excluding the subjects with the principal confounding factors, traffic police and controls were matched by age, working life, age of menarche, menstrual cycle day, BMI, drinking habits, habitual consumption of soy and Italian coffee. 68 traffic police and 82 controls (7th day; follicular phase of the ovarian cycle), 37 traffic police and 20 controls (21st day; lutheal phase of the ovarian cycle) were included in the study and matched for the above mentioned variables. In follicular and lutheal phase of ovarian cycle, 17-alpha-OH-P mean levels and the distribution of 17-alpha-OH-P values were significantly higher in traffic police vs. controls. A higher instance of mental health disorders in traffic police vs. controls was found, although the difference was not significant. Considering that the potential confounding effect of extraneous factors was controlled by restricting the study population and by matching traffic police vs. controls on the above mentioned variables, our results suggest that occupational exposure to urban pollutants may alter plasma 17-alpha-OH-P concentrations. 17-alpha-OH-P could be used in an occupational setting as an early biomarker of exposure to urban pollutants, valuable for a group, even before the onset of related pathologies.

Co-sleeping and childhood enuresis in China.

PubMed

Ma, Jun; Li, Shenghui; Jiang, Fan; Jin, Xingming; Shen, Xiaoming; Li, Fei

2014-01-01

Co-sleeping is associated with disturbance of the natural sleep pattern, including sleep fragmentation and daytime sleepiness. Nocturnal enuresis (NE) or bed-wetting, although benign, is a significant cause of distress to affected children and their caregiver(s). This study investigated the relationship between co-sleeping and NE in primary school children from China. Data from a previous sleep study of primary school children from 8 cities across China were analyzed. Multivariable regression analysis was performed to assess the relationship between co-sleeping and NE while controlling for a number of confounding factors. The prevalence of NE in co-sleeping and non-co-sleeping children in different age groups was evaluated. The prevalence of co-sleeping and NE in children aged 5 to 12 years was 22.8% and 4.6%, respectively. Co-sleeping was associated with a higher prevalence of NE in primary school age children (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.27-1.77; p < .001) after adjusting for confounding factors. The differences in the prevalence of NE between co-sleepers and non-co-sleepers were significant in the 9-year age group (OR, 1.49; 95% CI, 1.06-2.11; p = .025) and 11- to 12-year age group (OR, 3.16; 95% CI, 2.19-4.57; p < .001). Co-sleeping may increase the risk of NE in primary school children, particularly in those aged 11 to 12 years.

Labor patterns in twin gestations

PubMed Central

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

Testing for gene-environment interaction under exposure misspecification.

PubMed

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

2017-11-09

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

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

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

ERIC Educational Resources Information Center

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

2011-01-01

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

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

PubMed

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

2011-12-01

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

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

PubMed

Spears, Dean; Ghosh, Arabinda; Cumming, Oliver

2013-01-01

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

Effect of maternal age on the risk of preterm birth: A large cohort study

PubMed Central

Monet, Barbara; Ducruet, Thierry; Chaillet, Nils; Audibert, Francois

2018-01-01

Background Maternal age at pregnancy is increasing worldwide as well as preterm birth. However, the association between prematurity and advanced maternal age remains controversial. Objective To evaluate the impact of maternal age on the occurrence of preterm birth after controlling for multiple known confounders in a large birth cohort. Study design Retrospective cohort study using data from the QUARISMA study, a large Canadian randomized controlled trial, which collected data from 184,000 births in 32 hospitals. Inclusion criteria were maternal age over 20 years. Exclusion criteria were multiple pregnancy, fetal malformation and intra-uterine fetal death. Five maternal age categories were defined and compared for maternal characteristics, gestational and obstetric complications, and risk factors for prematurity. Risk factors for preterm birth <37 weeks, either spontaneous or iatrogenic, were evaluated for different age groups using multivariate logistic regression. Results 165,282 births were included in the study. Chronic hypertension, assisted reproduction techniques, pre-gestational diabetes, invasive procedure in pregnancy, gestational diabetes and placenta praevia were linearly associated with increasing maternal age whereas hypertensive disorders of pregnancy followed a “U” shaped distribution according to maternal age. Crude rates of preterm birth before 37 weeks followed a “U” shaped curve with a nadir at 5.7% for the group of 30–34 years. In multivariate analysis, the adjusted odds ratio (aOR) of prematurity stratified by age group followed a “U” shaped distribution with an aOR of 1.08 (95%CI; 1.01–1.15) for 20–24 years, and 1.20 (95% CI; 1.06–1.36) for 40 years and older. Confounders found to have the greatest impact were placenta praevia, hypertensive complications, and maternal medical history. Conclusion Even after adjustment for confounders, advanced maternal age (40 years and over) was associated with preterm birth. A maternal age of 30–34 years was associated with the lowest risk of prematurity. PMID:29385154

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

PubMed

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

2017-04-01

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

Effect of maternal age on the risk of preterm birth: A large cohort study.

PubMed

Fuchs, Florent; Monet, Barbara; Ducruet, Thierry; Chaillet, Nils; Audibert, Francois

2018-01-01

Maternal age at pregnancy is increasing worldwide as well as preterm birth. However, the association between prematurity and advanced maternal age remains controversial. To evaluate the impact of maternal age on the occurrence of preterm birth after controlling for multiple known confounders in a large birth cohort. Retrospective cohort study using data from the QUARISMA study, a large Canadian randomized controlled trial, which collected data from 184,000 births in 32 hospitals. Inclusion criteria were maternal age over 20 years. Exclusion criteria were multiple pregnancy, fetal malformation and intra-uterine fetal death. Five maternal age categories were defined and compared for maternal characteristics, gestational and obstetric complications, and risk factors for prematurity. Risk factors for preterm birth <37 weeks, either spontaneous or iatrogenic, were evaluated for different age groups using multivariate logistic regression. 165,282 births were included in the study. Chronic hypertension, assisted reproduction techniques, pre-gestational diabetes, invasive procedure in pregnancy, gestational diabetes and placenta praevia were linearly associated with increasing maternal age whereas hypertensive disorders of pregnancy followed a "U" shaped distribution according to maternal age. Crude rates of preterm birth before 37 weeks followed a "U" shaped curve with a nadir at 5.7% for the group of 30-34 years. In multivariate analysis, the adjusted odds ratio (aOR) of prematurity stratified by age group followed a "U" shaped distribution with an aOR of 1.08 (95%CI; 1.01-1.15) for 20-24 years, and 1.20 (95% CI; 1.06-1.36) for 40 years and older. Confounders found to have the greatest impact were placenta praevia, hypertensive complications, and maternal medical history. Even after adjustment for confounders, advanced maternal age (40 years and over) was associated with preterm birth. A maternal age of 30-34 years was associated with the lowest risk of prematurity.

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

PubMed Central

2013-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

Kuuranne, Tiia; Saugy, Martial; Baume, Norbert

2014-01-01

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

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

PubMed

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

2014-06-01

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

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

PubMed Central

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

2014-01-01

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

Socioeconomic status and risk of car crash injury, independent of place of residence and driving exposure: results from the DRIVE Study.

PubMed

Chen, H Y; Ivers, R Q; Martiniuk, A L C; Boufous, S; Senserrick, T; Woodward, M; Stevenson, M; Norton, R

2010-11-01

Previous studies that found increased crash risks for young drivers of low socioeconomic status (SES) have failed to adjust for factors such as driving exposure and rural residence. This aim of this study is to examine the independent effect of SES on crash risk, adjusting for such factors, and to examine the relationship between injury severity following a crash and SES. Information on risk factors for crash collected from 20,822 newly licenced drivers aged 17-24 years in New South Wales, Australia, as part of the DRIVE Study was prospectively linked to hospitalisation data. SES was classified as high, moderate or low based on the Australia 2001 Socio-Economic Index for Areas. Poisson regression was used to model risk of crash-related hospitalisation by SES, adjusting for confounders. Two measures of injury severity--urgency of treatment and length of hospital stay--were examined by SES. Results of multivariable analysis showed that drivers from low SES areas had increased relative risk (RR 1.8, 95% CI 1.1 to 3.1) of crash-related hospitalisation compared to drivers from high SES areas. This increased risk remained when adjusting for confounders including driving exposure and rurality (RR 1.9, 95% CI 1.1 to 3.2). No significant association was found between injury severity and SES. The higher risk of crash-related hospitalisation for young drivers from low SES areas is independent of driving exposure and rural-urban differences. This finding may help improve and better target interventions for youth of low SES.

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

PubMed

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

2016-01-01

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

Maternal pre-pregnancy BMI and intelligence quotient (IQ) in 5-year-old children: a cohort based study.

PubMed

Bliddal, Mette; Olsen, Jørn; Støvring, Henrik; Eriksen, Hanne-Lise F; Kesmodel, Ulrik S; Sørensen, Thorkild I A; Nøhr, Ellen A

2014-01-01

An association between maternal pre-pregnancy BMI and childhood intelligence quotient (IQ) has repeatedly been found but it is unknown if this association is causal or due to confounding caused by genetic or social factors. We used a cohort of 1,783 mothers and their 5-year-old children sampled from the Danish National Birth Cohort. The children participated between 2003 and 2008 in a neuropsychological assessment of cognitive ability including IQ tests taken by both the mother and the child. Linear regression analyses were used to estimate the associations between parental BMI and child IQ adjusted for a comprehensive set of potential confounders. Child IQ was assessed with the Wechsler Primary and Preschool Scales of Intelligence--Revised (WPPSI-R). The crude association between maternal BMI and child IQ showed that BMI was adversely associated with child IQ with a reduction in IQ of -0.40 point for each one unit increase in BMI. This association was attenuated after adjustment for social factors and maternal IQ to a value of -0.27 (-0.50 to -0.03). After mutual adjustment for the father's BMI and all other factors except maternal IQ, the association between paternal BMI and child IQ yielded a regression coefficient of -0.26 (-0.59 to 0.07), which was comparable to that seen for maternal BMI (-0.20 (-0.44 to 0.04)). Although maternal pre-pregnancy BMI was inversely associated with the IQ of her child, the similar association with paternal BMI suggests that it is not a specific pregnancy related adiposity effect.

Prolonged mounted patrolling is a risk factor for developing knee pain in Danish military personnel deployed to the Helmand Province.

PubMed

Lundin, Christina Rydahl; Houe, T; Sevelsted, A; Nissen, L

2016-10-01

Non-battle injuries have been the leading cause of medical evacuation in the recent wars in Afghanistan and Iraq. This study investigates the hypothesis, that the occurrence of knee problems could be associated with mounted patrolling in armoured vehicles independent of other risk factors. Retrospective questionnaire-based cohort study of Danish soldiers deployed to Afghanistan during 1 February-31 July 2013. 307 soldiers included. Response rate 70%. 33% reported knee pain. Significant association between knee pain and time spent weekly on mounted patrols (OR 1.23, CI 1.07 to 1.41, p=0.003). Controlled for confounders age, body mass index and duration of military employment (OR 1.22, CI 1.06 to 1.41, p=0.006). Adjusted for confounders and all other risk factors (OR 1.25, CI 1.07 to 1.48, p=0.007). The main finding in a subset of the 33% with knee pain: Significant association between more severe knee problems with Knee injury and Osteoarthritis Outcome Score below 400 and time spent weekly on mounted patrols (OR 1.49, CI 1.17 to 1.56, p=0.002). A major concern regarding knee problems among Danish deployed military personnel is identified. The risk of suffering from knee problems and the severity of symptoms increase with the amount of time spent inside a vehicle on mounted patrols. 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/

Drug safety analyses in a rheumatoid arthritis registry: application of different approaches regarding timing of exposure and confounder measurement.

PubMed

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.

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

PubMed Central

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

2012-01-01

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

A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

PubMed

Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

2009-12-01

Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors. 2009 Wiley-Liss, Inc.

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

PubMed

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

2016-06-01

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

Etiology of depression comorbidity in combat-related PTSD: a review of the literature.

PubMed

Stander, Valerie A; Thomsen, Cynthia J; Highfill-McRoy, Robyn M

2014-03-01

Posttraumatic stress disorder is often diagnosed with other mental health problems, particularly depression. Although PTSD comorbidity has been associated with more severe and chronic symptomology, relationships among commonly co-occurring disorders are not well understood. The purpose of this study was to review the literature regarding the development of depression comorbid with combat-related PTSD among military personnel. We summarize results of commonly tested hypotheses about the etiology of PTSD and depression comorbidity, including (1) causal hypotheses, (2) common factor hypotheses, and (3) potential confounds. Evidence suggests that PTSD may be a causal risk factor for subsequent depression; however, associations are likely complex, involving bidirectional causality, common risk factors, and common vulnerabilities. The unique nature of PTSD-depression comorbidity in the context of military deployment and combat exposure is emphasized. Implications of our results for clinical practice and future research are discussed. Published by Elsevier Ltd.

Experimental Design in Clinical 'Omics Biomarker Discovery.

PubMed

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.

Implant outcomes poorer in patients with history of periodontal disease.

PubMed

Veitz-Keenan, Analia; Keenan, James R

2017-03-01

Data sourcesMedline and Embase databases and bibliographies of all included articles and relevant review articles were screened for possible inclusion.Study selectionLongitudinal studies were included reporting on implant survival, success, incidence of peri-implantitis, bone loss and periodontal status and on partially dentate patients with a history of treatment for periodontitis. There were no language restrictions for the included studies.Data extraction and synthesisAuthors independently and in duplicate assessed the studies for eligibility and data extraction. Disagreements were resolved by discussion and consensus. The methodological quality assessment of the included studies was done using an adapted Newcastle-Ottawa Scale (NOS). Confounding factors such as smoking, systemic disease influencing osseointegration, chemotherapy and radiation were assessed and adjusted in the analysis. Data were organised into tables and grouped in accordance with the study design.ResultsTwenty-four studies reported in 27 publications were included. Implant survival and success rate were higher in periodontally healthy patients.Twelve prospective cohort studies, five case series with a control group, four retrospective cohort studies and three studies with a sub group comparison were included.Bone loss and peri-implantitis were increased in patients with a history of treated periodontitis. More complications were reported in patients presenting with more severe forms of periodontitis. High heterogeneity among the studies in terms of study design, population, therapy, unit of analysis, inconsistent definitions of baseline and outcomes, inadequate reporting and confounding factors meant a meta-analysis could not be performed.Most of the studies showed better implant survival rates for the non-periodontitis group ranging from 91.67% to 100% compared to the treated periodontitis group 79.22% to 100% over a 1.2 to 16 year follow-up.ConclusionsImplants placed in patients treated for periodontal disease are associated with higher incidence of biological complications and lower success and survival rates than those placed in periodontally healthy patients. Severe forms of periodontal disease are associated with higher rates of implant loss. The conclusion of the review is limited by the strength of the evidence.

Delayed heart rate recovery after exercise as a risk factor of incident type 2 diabetes mellitus after adjusting for glycometabolic parameters in men.

PubMed

Yu, Tae Yang; Jee, Jae Hwan; Bae, Ji Cheol; Hong, Won-Jung; Jin, Sang-Man; Kim, Jae Hyeon; Lee, Moon-Kyu

2016-10-15

Some studies have reported that delayed heart rate recovery (HRR) after exercise is associated with incident type 2 diabetes mellitus (T2DM). This study aimed to investigate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the development of T2DM including glucose-associated parameters as an adjusting factor in healthy Korean men. Analyses including fasting plasma glucose, HOMA-IR, HOMA-β, and HbA1c as confounding factors and known confounders were performed. HRR was calculated as peak heart rate minus heart rate after a 1-min rest (HRR 1). Cox proportional hazards model was used to quantify the independent association between HRR and incident T2DM. During 9082 person-years of follow-up between 2006 and 2012, there were 180 (10.1%) incident cases of T2DM. After adjustment for age, BMI, systolic BP, diastolic BP, smoking status, peak heart rate, peak oxygen uptake, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, HOMA-β, and HbA1c, the hazard ratios (HRs) [95% confidence interval (CI)] of incident T2DM comparing the second and third tertiles to the first tertile of HRR 1 were 0.867 (0.609-1.235) and 0.624 (0.426-0.915), respectively (p for trend=0.017). As a continuous variable, in the fully-adjusted model, the HR (95% CI) of incident T2DM associated with each 1 beat increase in HRR 1 was 0.980 (0.960-1.000) (p=0.048). This study demonstrated that delayed HRR after exercise predicts incident T2DM in men, even after adjusting for fasting glucose, HOMA-IR, HOMA-β, and HbA1c. However, only HRR 1 had clinical significance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth

PubMed Central

Feldstein Ewing, Sarah W.; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

Background A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. Methods For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Results Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Conclusions Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain. PMID:26958467

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth.

PubMed

Ewing, Sarah W Feldstein; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain.

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

PubMed

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

2013-04-01

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

DOT associated with reduced all-cause mortality among tuberculosis patients in Taipei, Taiwan, 2006–2008

PubMed Central

Yen, Y-F.; Rodwell, T. C.; Yen, M-Y.; Shih, H-C.; Hu, B-S.; Li, L-H.; Shie, Y-H.; Chuang, P.; Garfein, R. S.

2012-01-01

OBJECTIVE To determine whether patients receiving directly observed treatment (DOT) had lower all-cause mortality than those treated with self-administered treatment (SAT) and to identify factors associated with mortality among tuberculosis (TB) patients. DESIGN All TB patients in Taipei, Taiwan, diagnosed between 2006 and 2008 were included in a retrospective cohort study. RESULTS Among 3624 TB patients, 45.5% received DOT, which was disproptionately offered to older patients and those with more underlying illness and severe TB disease. After controlling for patient sociodemographic factors, clinical findings and underlying comorbidities, the odds of death was 40% lower (aOR 0.60, 95%CI 0.5–0.8) among patients treated with DOT than those on SAT. After adjusting for DOT, independent predictors of death included non-Taiwan birth, increasing age, male, unemployment, end-stage renal disease requiring dialysis, malignancy, acid-fast bacilli smear positivity and pleural effusion. CONCLUSION DOT was associated with lower all-cause mortality after controlling for confounding factors. DOT should be expanded in Taiwan to improve critical treatment outcomes among TB patients. PMID:22236917

Causal Methods for Observational Research: A Primer.

PubMed

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

2018-04-01

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

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

PubMed

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

2014-04-01

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

Directly observed therapy reduces tuberculosis-specific mortality: a population-based follow-up study in Taipei, Taiwan.

PubMed

Yen, Yung-Feng; Yen, Muh-Yong; Lin, Yi-Ping; Shih, Hsiu-Chen; Li, Lan-Huei; Chou, Pesus; Deng, Chung-Yeh

2013-01-01

To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB). All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006-2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome. Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30-0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65-79 and ≥80 years vs. 18-49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk. DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality.

Directly Observed Therapy Reduces Tuberculosis-Specific Mortality: A Population-Based Follow-Up Study in Taipei, Taiwan

PubMed Central

Yen, Yung-Feng; Yen, Muh-Yong; Lin, Yi-Ping; Shih, Hsiu-Chen; Li, Lan-Huei; Chou, Pesus; Deng, Chung-Yeh

2013-01-01

Objectives To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB). Methods All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006–2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome. Results Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30–0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65–79 and ≥80 years vs. 18–49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk. Conclusions DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality. PMID:24278152

The importance of inhaler devices: the choice of inhaler device may lead to suboptimal adherence in COPD patients.

PubMed

Darbà, Josep; Ramírez, Gabriela; Sicras, Antoni; Francoli, Pablo; Torvinen, Saku; Sánchez-de la Rosa, Rainel

2015-01-01

This study aims to identify factors associated with poor adherence to COPD treatment in patients receiving a fixed-dose combination (FDC) of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), focusing on the importance of inhaler devices. We conducted a retrospective and multicenter study based on a review of medical registries between 2007 and 2012 of COPD patients (n=1,263) treated with ICS/LABA FDC, whose medical devices were either dry powder inhalers (DPIs) or pressurized metered-dose inhalers (pMDI). Medication adherence included persistence outcomes through 18 months and medication possession ratios. Data on exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also included as confounders of adherence. The analyses revealed that COPD patients whose medication was delivered through a DPI were less likely to have medication adherence compared to patients with pMDI, after adjusting for confounding factors, especially active ingredients. Younger groups of patients were less likely to be adherent compared to the oldest group. Smoker men were less likely to be adherent compared to women and non-smokers. Comorbidities decreased the probability of treatment adherence. Those patients that visited their doctor once a month were more likely to adhere to their medication regimen; however, suboptimal adherence was more likely to occur among those patients who visited more than three times per month their doctor. We also found that worsening of COPD is negatively associated with adherence. According to this study, inhaler devices influence patients' adherence to long-term COPD medication. We also found that DPIs delivering ICS/LABA FDC had a negative impact on adherence. Patients' clinic and socioeconomic characteristics were associated with adherence.

Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies

USGS Publications Warehouse

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.

The influence of socioeconomic factors on gender disparities in lower extremity bypass.

PubMed

Sinnamon, Andrew J; Sonnenberg, Elizabeth M; Bartlett, Edmund K; Meise, Chelsey K; Wang, Grace J; Kelz, Rachel R

2014-05-15

Some contend that gender differences in outcomes after lower extremity bypass (LEB) for peripheral arterial disease (PAD) relate to socioeconomic factors (SEFs). Here, we evaluate these disparities with attention to clinically relevant yet understudied SEF. A retrospective cohort study of patients aged >50 y with PAD undergoing LEB was performed using data from Pennsylvania Health care and Cost Containment Council (2003-2011). Multivariable logistic regression modeling was performed to evaluate the association between gender and outcomes with adjustment for potential confounders including SEF such as income, insurance provider, distance to hospital, and race. Generalized estimating equations were used to adjust for hospital clustering. Independent models were developed to examine death or serious morbidity (DSM) and failure-to-rescue (FTR). Of 4202 patients identified, 1510 (36%) were women. SEF differed by gender. DSM was more frequent in women (15.6% versus 12.2%; P = 0.002). There was no association between gender and FTR in univariate analysis (P = 0.49). SEFs were associated with DSM and FTR. After adjustment for potential confounders including SEF, women remained more likely to experience DSM (odds ratio = 1.28; P = 0.01). There remained no significant association between gender and FTR on independent modeling (odds ratio = 0.49; P = 0.11). Women undergoing LEB in the state of Pennsylvania are at increased risk of poor outcomes, which is not completely explained by SEF. Quality of postoperative care does not appear to be different between gender as there was no difference in FTR. To improve these outcomes, efforts should be made to increase awareness of PAD and promote screening among high-risk women to ensure timely diagnosis and referral. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2009-04-01

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

Epidemiological research on radiation-induced cancer in atomic bomb survivors.

PubMed

Ozasa, Kotaro

2016-08-01

The late effects of exposure to atomic bomb radiation on cancer occurrence have been evaluated by epidemiological studies on three cohorts: a cohort of atomic bomb survivors (Life Span Study; LSS), survivors exposed IN UTERO : , and children of atomic bomb survivors (F1). The risk of leukemia among the survivors increased remarkably in the early period after the bombings, especially among children. Increased risks of solid cancers have been evident since around 10 years after the bombings and are still present today. The LSS has clarified the dose-response relationships of radiation exposure and risk of various cancers, taking into account important risk modifiers such as sex, age at exposure, and attained age. Confounding by conventional risk factors including lifestyle differences is not considered substantial because people were non-selectively exposed to the atomic bomb radiation. Uncertainty in risk estimates at low-dose levels is thought to be derived from various sources, including different estimates of risk at background levels, uncertainty in dose estimates, residual confounding and interaction, strong risk factors, and exposure to residual radiation and/or medical radiation. The risk of cancer in subjects exposed IN UTERO : is similar to that in LSS subjects who were exposed in childhood. Regarding hereditary effects of radiation exposure, no increased risk of cancers associated with parental exposure to radiation have been observed in the F1 cohort to date. In addition to biological and pathogenetic interpretations of the present results, epidemiological investigations using advanced technology should be used to further analyze these cohorts. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Pregnancy outcome of patients following bariatric surgery as compared with obese women: a population-based study.

PubMed

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.

Factors associated with dropout in medical education: a literature review.

PubMed

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.

Association between all-cause mortality and severity of depressive symptoms in patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS).

PubMed

Matsunaga, Satoshi; Tanaka, Shiro; Fujihara, Kazuya; Horikawa, Chika; Iimuro, Satoshi; Kitaoka, Masafumi; Sato, Asako; Nakamura, Jiro; Haneda, Masakazu; Shimano, Hitoshi; Akanuma, Yasuo; Ohashi, Yasuo; Sone, Hirohito

2017-08-01

The aims of this study are to confirm whether the excess mortality caused by depressive symptoms is independent of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and to evaluate the association between all-cause mortality and degrees of severity of depressive symptoms in Japanese patients with T2DM. A total of 1160 Japanese patients with T2DM were eligible for this analysis. Participants were followed prospectively for 3years and their depressive states were evaluated at baseline by the Center for Epidemiologic Studies Depression Scale (CES-D). Cox proportional hazards model was used to evaluate the relative risk of all-cause mortality and was adjusted by possible confounding factors, including severe hypoglycemia, all of which are known as risk factors for both depression and mortality. After adjustment for severe hypoglycemia, each 5-point increase in the CES-D score was significantly associated with excess all-cause mortality (hazard ratio 1.69 [95% CI 1.26-2.17]). The spline curve of HRs for mortality according to total CES-D scores showed that mortality risk was slightly increased at lower scores but was sharply elevated at higher scores. A high score on the CES-D at baseline was significantly associated with all-cause mortality in patients with T2DM after adjusting for confounders including severe hypoglycemia. However, only a small effect on mortality risk was found at relatively lower levels of depressive symptoms in this population. Further research is needed to confirm this relationship between the severity of depressive symptoms and mortality in patients with T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between altitude and lithium in groundwater in the United States of America: results of a 1992-2003 study.

PubMed

Huber, Rebekah S; Kim, Namkug; Renshaw, Carl E; Renshaw, Perry F; Kondo, Douglas G

2014-11-01

Therapeutic dosages of lithium are known to reduce suicide rates, which has led to investigations of confounding environmental risk factors for suicide such as lithium in groundwater. It has been speculated that this might play a role in the potential relationship between suicide and altitude. A recent study in Austria involving geospatial analysis of lithium in groundwater and suicide found lower levels of lithium at higher altitudes. Since there is no reason to suspect this correlation is universal given variation in geology, the current study set out to investigate the relationship between altitude and lithium in groundwater in the United States of America (USA). The study utilised data extracted from the National Water-Quality Assessment programme implemented by the United States Geological Survey that has collected 5,183 samples from 48 study areas in USA for the period of 1992 to 2003. Lithium was the trace-element of interest and 518 samples were used in the current analyses. Due to uneven lithium sampling within the country, only the states (n=15) with the highest number of lithium samples were included. Federal information processing standard codes were used to match data by county with the mean county altitude calculated using altitude data from the Shuttle Radar Topography Mission. The study was controlled for potential confounding factors known to affect levels of lithium in groundwater including aquifer, aquifer type, lithology, water level and the depths of wells. The levels of lithium in groundwater, increased with altitude (R(2) = 0.226, P <0.001) during the study period. These findings differ from the Austrian study and suggest a need for further research accounting also for the impact of geographical variation.

Errors in Martian paleodischarges skew interpretations of hydrologic history: Case study of the Aeolis Dorsa, Mars, with insights from the Quinn River, NV

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.

The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer.

PubMed

Winn, D M; Lee, Y-C A; Hashibe, M; Boffetta, P

2015-09-01

The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors associated with higher oxytocin requirements in labor.

PubMed

Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

2015-09-01

To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

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

ERIC Educational Resources Information Center

Tamanja, Emmanuel Makabu J.

2016-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

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

2014-12-16

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

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

PubMed

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

2014-05-01

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

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

PubMed

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

2007-01-01

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

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

PubMed

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

2004-01-01

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

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

PubMed

Takeuchi, Yoshinori; Shinozaki, Tomohiro; Matsuyama, Yutaka

2018-01-08

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

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

DTIC Science & Technology

1986-04-01

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

The development of a modified spectral ripple test.

PubMed

Aronoff, Justin M; Landsberger, David M

2013-08-01

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

Adult Body Height Is a Good Predictor of Different Dimensions of Cognitive Function in Aged Individuals: A Cross-Sectional Study.

PubMed

Pereira, Vitor H; Costa, Patrício S; Santos, Nadine C; Cunha, Pedro G; Correia-Neves, Margarida; Palha, Joana A; Sousa, Nuno

2016-01-01

Background: Adult height, weight, and adiposity measures have been suggested by some studies to be predictors of depression, cognitive impairment, and dementia. However, the presence of confounding factors and the lack of a thorough neuropsychological evaluation in many of these studies have precluded a definitive conclusion about the influence of anthropometric measures in cognition and depression. In this study we aimed to assess the value of height, weight, and abdominal perimeter to predict cognitive impairment and depressive symptoms in aged individuals. Methods and Findings: Cross-sectional study performed between 2010 and 2012 in the Portuguese general community. A total of 1050 participants were included in the study and randomly selected from local area health authority registries. The cohort was representative of the general Portuguese population with respect to age (above 50 years of age) and gender. Cognitive function was assessed using a battery of tests grouped in two dimensions: general executive function and memory. Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood before and after correction for possible confounding factors (gender, age, school years, physical activity, alcohol consumption, and smoking habits). We found single associations of weight, height, body mass index, abdominal perimeter, and age with executive function, memory and depressive symptoms. However, when included in a predictive model adjusted for gender, age, school years, and lifestyle factors only height prevailed as a significant predictor of general executive function (β = 0.139; p < 0.001) and memory (β = 0.099; p < 0.05). No relation was found between mood and any of the anthropometric measures studied. Conclusions and Relevance: Height is an independent predictor of cognitive function in late-life and its effects on the general and executive function and memory are independent of age, weight, education level, gender, and lifestyle factors. Altogether, our data suggests that modulators of adult height during childhood may irreversibly contribute to cognitive function in adult life and that height should be used in models to predict cognitive performance.

Is male factor infertility associated with midlife low-grade inflammation? A population based study.

PubMed

Hærvig, Katia Keglberg; Kierkegaard, Lene; Lund, Rikke; Bruunsgaard, Helle; Osler, Merete; Schmidt, Lone

2018-06-01

Male factor infertility is associated with an increased risk of disease and mortality, which has been related to markers of chronic systemic inflammation. The objective of this study was to investigate the association between male factor infertility and low-grade inflammation and furthermore to examine the lifetime prevalence of male factor infertility and overall infertility (also including female and couple infertility). The study population consisted of 2140 members of the Metropolit 1953 Danish Male Birth Cohort who had participated in the Copenhagen Aging and Midlife Biobank data collection in 2009-2011. Information on male factor infertility and overall infertility was obtained from a questionnaire, and low-grade inflammation was evaluated as the highest plasma levels of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha in the population. The level of interleukin-6 was significantly higher among men with male factor infertility compared with other men adjusted for potential confounders. This was not found for the two other inflammatory markers. The lifetime prevalence of male factor infertility and overall infertility were 10.2% and 17.9%, respectively. The findings suggest that male factor infertility might be associated with an increased level of interleukin-6.

Proton-pump inhibitors: understanding the complications and risks.

PubMed

Malfertheiner, Peter; Kandulski, Arne; Venerito, Marino

2017-12-01

Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.

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

PubMed

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

2017-12-28

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

Osteoporosis in adult patients with atopic dermatitis: A nationwide population-based study

PubMed Central

Lu, Chun-Ching; Su, Yu-Feng; Tsai, Tai-Hsin; Wu, Chieh-Hsin

2017-01-01

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. PMID:28207767

The association between anthropometric measures and lung function in a population-based study of Canadian adults.

PubMed

Rowe, A; Hernandez, P; Kuhle, S; Kirkland, S

2017-10-01

Decreased lung function has health impacts beyond diagnosable lung disease. It is therefore important to understand the factors that may influence even small changes in lung function including obesity, physical fitness and physical activity. The aim of this study was to determine the anthropometric measure most useful in examining the association with lung function and to determine how physical activity and physical fitness influence this association. The current study used cross-sectional data on 4662 adults aged 40-79 years from the Canadian Health Measures Survey Cycles 1 and 2. Linear regression models were used to examine the association between the anthropometric and lung function measures (forced expiratory volume in 1 s [FEV 1 ] and forced vital capacity [FVC]); R 2 values were compared among models. Physical fitness and physical activity terms were added to the models and potential confounding was assessed. Models using sum of 5 skinfolds and waist circumference consistently had the highest R 2 values for FEV 1 and FVC, while models using body mass index consistently had among the lowest R 2 values for FEV 1 and FVC and for men and women. Physical activity and physical fitness were confounders of the relationships between waist circumference and the lung function measures. Waist circumference remained a significant predictor of FVC but not FEV 1 after adjustment for physical activity or physical fitness. Waist circumference is an important predictor of lung function. Physical activity and physical fitness should be considered as potential confounders of the relationship between anthropometric measures and lung function. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed

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

2014-08-01

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

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

PubMed

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.

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

PubMed Central

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

2016-01-01

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

Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies.

PubMed

Braga, J R; Santos, I S O; McDonald, M; Shah, P S; Ross, H J

2012-01-01

Cardiac allograft vasculopathy (CAV) is a significant factor impacting outcomes after heart transplant. We performed a systematic review of risk factors for the development of CAV. A search of electronic databases was performed. The eligibility criteria included cohort and case-control studies with more than 50 adult patients submitted to a heart transplant. The outcome should be CAV diagnosed by angiography and/or intravascular ultrasound (IVUS). Two reviewers performed study selection, data abstraction, and quality assessment. Of 2514 citations, 66 articles were included--46 had 200 participants or less; 61 were single-center; and 44 were retrospective cohorts. The most used definition of CAV using angiography was the detection of any degree of abnormality (21 studies of 58). In studies using IVUS, an intimal thickness ≥0.5 mm was the most used definition (five of eight studies). Quality assessment revealed an inadequate description of patient selection, attrition, and accounting of potential confounders. Donor age, recipient age, recipient gender, etiology of heart failure, ischemic time, human leukocyte antigen matching, cytomegalovirus, lipid profile, and rejection episodes were the most studied factors. Our review indicates that the current evidence is not consistent across different studies. The definite contribution of risk factors for the development of CAV is still to be determined. © 2011 John Wiley & Sons A/S.

Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review.

PubMed

Møller, Morten Hylander; Adamsen, Sven; Thomsen, Reimar Wernich; Møller, Ann Merete

2010-08-01

Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.

The relationship between labor unions and safety in US airlines: Is there a "union effect?"

NASA Astrophysics Data System (ADS)

Zapf, Renee Catherine

Every airline union claims to work for safety and presents anecdotes where greater airline safety has been achieved through union efforts. The effect unionization has on safety outcomes in U.S. commercial airlines, however, wasn't found to be previously tested. Studies have shown that in industries such as coal mining, retail, and construction, unionization does lead to an increase in safety. This study evaluated the safety rates of 15 major US commercial airlines to compare the difference between unionized and non-unionized airlines. These safety rates were compared based on if and how long each airline's pilots and flight attendants have been unionized, to determine if unionization had an effect on safety outcomes. The 15 airlines included in the study identified as operating most of the years between 1990 and 2013, with annual departures averaging over 130,000, available through the Bureau of Transportation Statistics. Accident and Incident information was acquired through the National Transportation Safety Board database. The number of accident and incidents divided by the total departures at each airline was used as the safety rate. Union websites provided information on unionization at the airlines. Due to the complex nature of the aviation industry, a number of confounding factors could have affected the tests, including mergers, route structures, and legislation. To help control for these confounding factors, this study was limited to airlines with a stable presence in the industry over time, which limited the number of airlines included. No significant difference was found between unionized and non-unionized airlines in this study, though the mean safety rate of unionized airlines was found be better than non-unionized airlines. This study did not take into account safety improvements that were union-backed and eventually required at all airlines, regardless of unionization. Due to the large sample size of the small population the difference in safety rate means could be indicative of greater safety in unionized airlines.

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

PubMed

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

2017-03-01

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

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

PubMed

Ullemar, V; Lundholm, C; Almqvist, C

2015-08-01

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

EVALUATION AND MANAGEMENT OF ANEMIA IN THE ELDERLY

PubMed Central

Goodnough, Lawrence Tim; Schrier, Stanley L.

2015-01-01

Anemia is now recognized as a risk factor for a number of adverse outcomes in the elderly, including hospitalization, morbidity, and mortality. What constitutes appropriate evaluation and management for an elderly patient with anemia, and when to initiate a referral to a hematologist, are significant issues. Attempts to identify suggested hemoglobin levels for blood transfusion therapy have been confounded for elderly patients with their co-morbidities. Since no specific recommended hemoglobin threshold has stood the test of time, prudent transfusion practices to maintain hemoglobin thresholds of 9–10 g/dl in the elderly are indicated, unless or until evidence emerges to indicate otherwise. PMID:24122955

Parental History of Type 2 Diabetes in Patients with Nonaffective Psychosis

PubMed Central

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

2009-01-01

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

Coronary Artery Calcification in Japanese Men in Japan and Hawaii

PubMed Central

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

2013-01-01

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

Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics.

PubMed

Ananth, Cande V; Schisterman, Enrique F

2017-08-01

Prospective and retrospective cohorts and case-control studies are some of the most important study designs in epidemiology because, under certain assumptions, they can mimic a randomized trial when done well. These assumptions include, but are not limited to, properly accounting for 2 important sources of bias: confounding and selection bias. While not adjusting the causal association for an intermediate variable will yield an unbiased estimate of the exposure-outcome's total causal effect, it is often that obstetricians will want to adjust for an intermediate variable to assess if the intermediate is the underlying driver of the association. Such a practice must be weighed in light of the underlying research question and whether such an adjustment is necessary should be carefully considered. Gestational age is, by far, the most commonly encountered variable in obstetrics that is often mislabeled as a confounder when, in fact, it may be an intermediate. If, indeed, gestational age is an intermediate but if mistakenly labeled as a confounding variable and consequently adjusted in an analysis, the conclusions can be unexpected. The implications of this overadjustment of an intermediate as though it were a confounder can render an otherwise persuasive study downright meaningless. This commentary provides an exposition of confounding bias, collider stratification, and selection biases, with applications in obstetrics and perinatal epidemiology. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2007-03-01

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

A cross-sectional study to estimate associations between education level and osteoporosis in a Chinese postmenopausal women sample.

PubMed

Piao, Hui-Hong; He, Jiajia; Zhang, Keqin; Tang, Zihui

2015-01-01

Our research aims to investigate the associations between education level and osteoporosis (OP) in Chinese postmenopausal women. A large-scale, community-based, cross-sectional study was conducted to examine the associations between education level and OP. A self-reported questionnaire was used to access the demographical information and medical history of the participants. A total of 1905 postmenopausal women were available for data analysis in this study. Multiple regression models controlling for confounding factors to include education level were performed to investigate the relationship with OP. The prevalence of OP was 28.29% in our study sample. Multivariate linear regression analyses adjusted for relevant potential confounding factors detected significant associations between education level and T-score (β = 0.025, P-value = 0.095, 95% CI: -0.004-0.055 for model 1; and β = 0.092, P-value = 0.032, 95% CI: 0.008-0.175 for model 2). Multivariate logistic regression analyses detected significant associations between education level and OP in model 1 (P-value = 0.070 for model 1, Table 5), while no significant associations was reported in model 2 (P value = 0.131). In participants with high education levels, the OR for OP was 0.914 (95% CI: 0.830-1.007). The findings indicated that education level was independently and significantly associated with OP. The prevalence of OP was more frequent in Chinese postmenopausal women with low educational status.

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

PubMed

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

2018-02-01

Osteoporosis is considered a public health problem with high worldwide prevalence. One approach to prevention is through the promotion of physical activity, especially exercise, during adolescence. This study compared bone variables in different body segments in adolescents according to participation in track and field. The study included 34 adolescents (22 boys), of whom 17 were track and field athletes and 17 were control subjects. Bone mineral density (BMD, g/cm 2 ) and bone mineral content (BMC, g) were analyzed using dual energy X-ray absorptiometry (total body stratified by body segments). Peak height velocity was used to estimate somatic maturation. Athletes had higher BMD ( P =0.003) and BMC ( P =0.011) values in the lower limbs and higher whole body BMD ( P =0.025) than the control group. However, when adjusted for confounding factors, the difference was not maintained. The groups had similar lean soft tissue values ( P =0.094). Training overload was positively correlated with BMD in the upper limbs (r=0.504; 95% confidence interval, 0.031-0.793). Although track and field athletes had higher BMD and BMC values in the lower limbs, these differences were not significant when adjusted for confounding factors. Track and field participation in adolescence appears to influence BMD and BMC in lower limbs, and fat-free mass seems to mediate this effect. Also, higher training loads were found to be positive for bone health in upper limbs.

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

PubMed Central

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

2018-01-01

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

Age-related changes in humoral and cell-mediated immunity in Down syndrome children living at home.

PubMed

Lockitch, G; Singh, V K; Puterman, M L; Godolphin, W J; Sheps, S; Tingle, A J; Wong, F; Quigley, G

1987-11-01

Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 micrograms/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.

Impact of breastfeeding on the intelligence quotient of eight-year-old children.

PubMed

Fonseca, Ana L M; Albernaz, Elaine P; Kaufmann, Cristina C; Neves, Ivana H; Figueiredo, Vera L M de

2013-01-01

This study aimed to determine the influence of breastfeeding on the intellectual capacity of children from a cohort in a developing country, with a control for the main confounding factors. A prospective cohort study was performed including all infants born in the hospitals of a medium-size city, and a random sample of these newborns was monitored at 30, 90, and 180 days of life, and at age 8 years. Several aspects of breastfeeding were assessed in the follow-up and, at 8 years, general intellectual capacity was assessed through the Raven's Colored Progressive Matrices test. The statistical analyses used Student's t-test, ANOVA, and linear regression and logistics, considering p-values less than 0.05 as statistically significant associations. At age 8 years, 560 children were assessed with Raven's Colored Progressive Matrices test. The average score was 22.56 points, with a standard deviation of 5.93. The difference in the averages found between the breastfed and non-breastfed groups at six months of age was 1.33 (p=0.008). Mother's and child's skin color, social and economic class, maternal education and smoking, and breastfeeding at six months of age (p=0.007) were still associated with the outcome. Children that were breastfed for six months or more had better performance in the general intellectual assessment, even after adjusting for the main confounding factors. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

PubMed

Bagshaw, Andrew T M; Horwood, L John; Fergusson, David M; Gemmell, Neil J; Kennedy, Martin A

2017-02-03

The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-β) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-β gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p < 0.001), and of self-reported criminal behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. The potential functional importance of the TBR1 gene's promoter microsatellite deserves further investigation. Our results suggest that it participates in a gene-environment interaction with MDSP and antisocial behaviour. However, previous evidence that mothers who smoke during pregnancy carry genes for antisocial behaviour suggests that epistasis may influence the interaction.

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

Guendelman, S; Silberg, M J

1993-01-01

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

Religion and mortality among the community-dwelling elderly.

PubMed Central

Oman, D; Reed, D

1998-01-01

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

Egg consumption and the risk of type 2 diabetes mellitus: a case-control study.

PubMed

Radzevičienė, Lina; Ostrauskas, Rytas

2012-08-01

Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. A case-control study in a Lithuanian out-patient clinic was performed in 2001. A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.

Waterpipe Use and Susceptibility to Cigarette Smoking Among Never-Smoking Youth.

PubMed

Veeranki, Sreenivas P; Alzyoud, Sukaina; Kheirallah, Khalid A; Pbert, Lori

2015-10-01

Susceptibility to cigarette smoking, defined as the lack of a firm decision against smoking, is a strong predictor of regular smoking and addiction. Several modifiable risk factors have been identified among never cigarette smokers, and one potential factor of interest is waterpipe use. The purpose of this study is to determine the association of waterpipe use with susceptibility to cigarette smoking among never-smoking youth. In a pooled analysis of 17 Arab nations with nationally representative Global Youth Tobacco Surveys conducted during 2002-2011, tobacco-related information was obtained from 30,711 never-smoking adolescents representing 4,962,872 youth. Study outcome was susceptibility to cigarette smoking, and primary exposure was waterpipe use. Data were analyzed in 2014 using weighted logistic regression models, including stratified models by gender, to determine the odds of susceptibility to cigarette smoking with waterpipe use, adjusting for confounders. Overall, 20% of never-smoking youth were susceptible to cigarette smoking, ranging from 13.1% in Oman to 32.6% in Somalia; 5.2% currently used waterpipe, ranging from 0.3% in Morocco to 23.5% in Kuwait. The estimated odds of susceptibility to cigarette smoking were 2.5 (95% CI=1.9, 3.4) times higher for adolescents who used waterpipe in the past month compared with those who did not, controlling for confounders. Estimates were similar when stratified by gender. Waterpipe use is associated with susceptibility to cigarette smoking. Study findings identify a novel risk factor for never smokers to initiate smoking and will help the public health community develop and implement policies around waterpipe use prevention. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Individual contributions of visceral fat and total body fat to subclinical atherosclerosis: The NEO study.

PubMed

Gast, Karin B; den Heijer, Martin; Smit, Johannes W A; Widya, Ralph L; Lamb, Hildo J; de Roos, Albert; Jukema, J Wouter; Rosendaal, Frits R; de Mutsert, Renée

2015-08-01

Both overall and abdominal adiposity are established risk factors for cardiovascular disease. Visceral adipose tissue (VAT) and total body fat (TBF) are strongly correlated and previous studies did not make this distinction. We aimed to distinguish individual contributions of TBF, VAT, and the ratio of VAT to abdominal subcutaneous adipose tissue (VAT/SAT) to subclinical atherosclerosis in men and women. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, we assessed VAT and SAT with magnetic resonance imaging, TBF with bio-electrical impendence analysis, and carotid Intima-Media Thickness (cIMT) with ultrasound. We performed linear regression analyses of standardized values of TBF, VAT, VAT/SAT with cIMT. We adjusted the models for confounding factors (age, sex, ethnicity, education, smoking, alcohol, physical activity), and either for VAT or TBF. This analysis included 2451 participants, 53% men with mean (SD) cIMT of 615 (91)μm. After adjustment for confounding factors, the difference in cIMT (95% CI) per SD in VAT was 14 (8,21)μm in men and 18 (13,24)μm in women. After adjustment for TBF, this attenuated to 5 (-3,13)μm in men and 13 (5,20)μm in women. In the full model, differences in cIMT (95% CI) per SD of TBF were 14 (6,22)μm in men and 8 (0,16)μm in women, and per SD of VAT/SAT were 7 (-1,15)μm and 9 (3,16)μm respectively. In this population-based study, VAT contributed beyond overall adiposity to subclinical atherosclerosis, particularly in women. This implies a specific role of VAT in the early development of atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The 'bioscience problem' for nursing students: an integrative review of published evaluations of Year 1 bioscience, and proposed directions for curriculum development.

PubMed

McVicar, Andrew; Andrew, Sharon; Kemble, Ross

2015-03-01

The difficulties that nursing students have in learning human biosciences have given cause for concern for over 20 years but the problem remains. To conduct an integrative review of published primary research into the 'bioscience problem', evaluate their outcomes, and provide a contemporary analysis of potential directions for curriculum planners. A systematic search of electronic databases CINAHL, Medline, British Nursing Index and Google Scholar was conducted for empirical research studies, published between 1990 and 2013, designed to either predict performance of students in bioscience assessments in Year 1 of their studies or identify in-course curriculum delivery issues. The search generated nineteen papers that met inclusion criteria. Twelve papers involved predictive factors for bioscience attainment and seven surveyed student views on curriculum issues. Four others that surveyed reflections of later-year students or qualified nurses on Year 1 outcomes were also retained for additional context. Prediction based on pre-admission academic achievement was not reliable. Student factors including age at entry, self-efficacy in science, and having appropriate study skills in particular appear to be confounding factors. In-course influences such as teaching strategy or lecturer skills are also inconsistent and likely to represent confounders operating at local, institutional level. The integrative review approach enabled analysis of incongruencies between studies that have been a barrier to curriculum development. Sound admissions criteria based on pre-university academic performance show promise in resolving the 'bioscience problem' but will likely be contingent on innovative support early in Year 1 for study skills and the fundamentals of human bioscience, plus attention to local quality assurance for curriculum delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Part-time work or social benefits as predictors for disability pension: a prospective study of Swedish twins.

PubMed

Ropponen, Annina; Alexanderson, Kristina; Svedberg, Pia

2014-04-01

To a large extent, it is unknown whether work absences other than sickness absence (SA) covered by social benefits such as parental leave, rehabilitation, or unemployment would predict disability pension (DP). We investigated whether part-time work or having received social benefits for sick leave, rehabilitation, or parental leave would be predictors for DP taking into account familial confounding (genetics and shared environment, e.g., social background) in these associations. A sample of 17,640 same-sex Swedish twin ndividuals [corrected] was followed from 2000 to 2008 via national registries for their receipt of social benefits and DP including additional baseline questionnaire data. Cox proportional hazard ratios were estimated. Full-time work was less common (47 %) among those being granted DP during the follow-up compared to those without DP (69 %). Self-reported full-time work, part-time work (≥50 %), and self-employment and registry data of caring for a child were the direct protective factors, whereas self-reported part-time work (<50 %) and long-term SA and registry data on SA, compensation for rehabilitation, and benefits during return to work were the direct risk factors for DP, i.e., independent of familial confounding. Part-time work and social benefits play different roles in predicting DP. Thus, full-time work, part-time work (≥50 %), self-employment, and benefits for parental leave seem to protect from DP. In contrast, SA and part-time work (<50 %) carry a highly increased risk for DP. Although these associations were mainly independent from several mediating factors, some of the associations seem to be influenced by family situation, social benefits, or severity of diseases.

Assessing the determinants of evolutionary rates in the presence of noise.

PubMed

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-06-01

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

Three Mile Island epidemiologic radiation dose assessment revisited: 25 years after the accident.

PubMed

Field, R William

2005-01-01

Over the past 25 years, public health concerns following the Three Mile Island (TMI) accident prompted several epidemiologic investigations in the vicinity of TMI. One of these studies is ongoing. This commentary suggests that the major source of radiation exposure to the population has been ignored as a potential confounding factor or effect modifying factor in previous and ongoing TMI epidemiologic studies that explore whether or not TMI accidental plant radiation releases caused an increase in lung cancer in the community around TMI. The commentary also documents the observation that the counties around TMI have the highest regional radon potential in the United States and concludes that radon progeny exposure should be included as part of the overall radiation dose assessment in future studies of radiation-induced lung cancer resulting from the TMI accident.

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

PubMed

Jackson, John W

2016-11-01

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

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

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

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

1995-12-31

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

A Vision for an International Multi-Sensor Snow Observing Mission

NASA Technical Reports Server (NTRS)

Kim, Edward

2015-01-01

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

Why Assembling Plant Genome Sequences Is So Challenging

PubMed Central

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

2012-01-01

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

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

PubMed

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

2016-05-01

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

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

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

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

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

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

Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies.

PubMed

Flegr, Jaroslav; Lindová, Jitka; Pivoñková, Vera; Havlícek, Jan

2008-12-01

A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence. (c) 2008 Wiley-Liss, Inc.

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

PubMed

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

2016-06-03

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

Childhood Medical and Behavioral Consequences of Maternal Cocaine Use1

PubMed Central

Singer, Lynn; Farkas, Kathleen; Kliegman, Robert

2014-01-01

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

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

PubMed

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

2014-05-01

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

Effectiveness of electronic stability control on single-vehicle accidents.

PubMed

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

2015-01-01

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

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

PubMed Central

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

2010-01-01

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

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

ERIC Educational Resources Information Center

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

2013-01-01

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

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

ERIC Educational Resources Information Center

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

2012-01-01

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

WHAT TO DO IF THERE IS NO REFERENCE SYSTEM

EPA Science Inventory

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

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

PubMed

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

2013-11-01

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

A Review of Covariate Selection for Nonexperimental Comparative Effectiveness Research

PubMed Central

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

2014-01-01

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

Effectiveness and confounding factors of penetrating astigmatic keratotomy in clinical practice

PubMed Central

Yen, Chu-Yu; Tseng, Gow-Lieng

2018-01-01

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

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

PubMed

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

2017-08-01

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

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

PubMed Central

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

2012-01-01

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

Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.

PubMed

Larivée, N; Suissa, S; Khosrow-Khavar, F; Tagalakis, V; Filion, K B

2017-09-01

The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial. To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs. We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index. Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French. We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding. Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57. As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk. Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel). © 2017 Royal College of Obstetricians and Gynaecologists.

Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change.

PubMed

Darmon, Michael; Diconne, Eric; Souweine, Bertrand; Ruckly, Stéphane; Adrie, Christophe; Azoulay, Elie; Clec'h, Christophe; Garrouste-Orgeas, Maïté; Schwebel, Carole; Goldgran-Toledano, Dany; Khallel, Hatem; Dumenil, Anne-Sylvie; Jamali, Samir; Cheval, Christine; Allaouchiche, Bernard; Zeni, Fabrice; Timsit, Jean-François

2013-01-21

To assess the prevalence of dysnatremia, including borderline changes in serum sodium concentration, and to estimate the impact of these dysnatremia on mortality after adjustment for confounders. Observational study on a prospective database fed by 13 intensive care units (ICUs). Unselected patients with ICU stay longer than 48 h were enrolled over a 14-year period were included in this study. Mild to severe hyponatremia were defined as serum sodium concentration < 135, < 130, and < 125 mmol/L respectively. Mild to severe hypernatremia were defined as serum sodium concentration > 145, > 150, and > 155 mmol/L respectively. Borderline hyponatremia and hypernatremia were defined as serum sodium concentration between 135 and 137 mmol/L or 143 and 145 respectively. A total of 11,125 patients were included in this study. Among these patients, 3,047 (27.4%) had mild to severe hyponatremia at ICU admission, 2,258 (20.3%) had borderline hyponatremia at ICU admission, 1,078 (9.7%) had borderline hypernatremia and 877 (7.9%) had mild to severe hypernatremia. After adjustment for confounder, both moderate and severe hyponatremia (subdistribution hazard ratio (sHR) 1.82, 95% CI 1.002 to 1.395 and 1.27, 95% CI 1.01 to 1.60 respectively) were associated with day-30 mortality. Similarly, mild, moderate and severe hypernatremia (sHR 1.34, 95% CI 1.14 to 1.57; 1.51, 95% CI 1.15 to 1.99; and 2.64, 95% CI 2.00 to 3.81 respectively) were independently associated with day-30 mortality. One-third of critically ill patients had a mild to moderate dysnatremia at ICU admission. Dysnatremia, including mild changes in serum sodium concentration, is an independent risk factor for hospital mortality and should not be neglected.

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

PubMed

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

2014-12-10

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2009-01-01

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

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

PubMed Central

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

2015-01-01

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

On the importance of controlling for effort in analysis of count survey data: Modeling population change from Christmas Bird Count data

USGS Publications Warehouse

Link, W.A.; Sauer, J.R.; Helbig, Andreas J.; Flade, Martin

1999-01-01

Count survey data are commonly used for estimating temporal and spatial patterns of population change. Since count surveys are not censuses, counts can be influenced by 'nuisance factors' related to the probability of detecting animals but unrelated to the actual population size. The effects of systematic changes in these factors can be confounded with patterns of population change. Thus, valid analysis of count survey data requires the identification of nuisance factors and flexible models for their effects. We illustrate using data from the Christmas Bird Count (CBC), a midwinter survey of bird populations in North America. CBC survey effort has substantially increased in recent years, suggesting that unadjusted counts may overstate population growth (or understate declines). We describe a flexible family of models for the effect of effort, that includes models in which increasing effort leads to diminishing returns in terms of the number of birds counted.

Does aircraft noise exposure increase the risk of hypertension in the population living near airports in France?

PubMed

Evrard, Anne-Sophie; Lefèvre, Marie; Champelovier, Patricia; Lambert, Jacques; Laumon, Bernard

2017-02-01

The largest study until now around 6 major European airports, the HYENA (HYpertension and Exposure to Noise near Airports) study, reported an excess risk of hypertension related to long-term aircraft noise exposure. The DEBATS (Discussion on the health effects of aircraft noise) study investigated the relationship between this exposure and the risk of hypertension in men and in women near French airports. Blood pressure of 1244 participants older than 18 years of age was measured. Information about health, socioeconomic and lifestyle factors was collected by means of a face-to-face questionnaire performed at home by an interviewer. Aircraft noise exposure was assessed for each participant's home address using noise maps. They were calculated with the Integrated Noise Model with a 1 dB(A)-resolution. The major potential confounders being risk factors for hypertension were included in the logistic regression models: age, occupational activity, body mass index, physical activity and alcohol consumption. After adjustment for the main potential confounders, an exposure-response relationship was evidenced between the risk of hypertension and aircraft noise exposure at night for men only. A 10-dB(A) increase in L night was associated with an OR of 1.34 (95% CI 1.00 to 1.97). These findings contribute to the overall evidence suggesting that aircraft noise exposure at night-time may increase the risk of hypertension in men. Hypertension is a well-known and established risk factor for cardiovascular disease. The association reported in the present study between aircraft noise and hypertension implies that aircraft noise might be a risk factor also for cardiovascular disease. 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/.

Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

PubMed

Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

2016-01-01

Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the developing infant gut microbiome.

Adding Salt to Meals as a Risk Factor of Type 2 Diabetes Mellitus: A Case-Control Study.

PubMed

Radzeviciene, Lina; Ostrauskas, Rytas

2017-01-13

Type 2 diabetes mellitus (T2DM) is thought to arise from the complex interplay between genetic and environmental factors. It is important to identify modifiable risk factors that may help to reduce the risk of diabetes. Data on salt intake and the risk of type 2 diabetes are limited. The aim of this study was to assess the relationship between adding salt to prepared meals and the risk of type 2 diabetes. In a case-control study, we included 234 cases, all of whom were patients aged 35-86 years with a newly confirmed diagnosis of T2DM, and 468 controls that were free of the disease. Cases and controls (ratio 1:2) were matched by gender and age (±5 years). A questionnaire was used to collect information on possible risk factors for diabetes. Adding salt to prepared meals was assessed according to: Never, when there was not enough, or almost every time without tasting. The odds ratios (OR), and 95% confidence intervals (CI) for type 2 diabetes was calculated using a conditional logistic regression. The cases had a higher body mass index and a significantly lower education level compared to the controls. Variables such as waist circumference, body mass index, eating speed, smoking, family history of diabetes, arterial hypertension, plasma triglycerides, educational level, occupational status, morning exercise, marital status, daily urine sodium excretion, and daily energy intake were retained in the models as confounders. After adjusting for possible confounders, an approximately two-fold increased risk of type 2 diabetes was determined in subjects who add salt to prepared meals when "it is not enough" or "almost every time without tasting" (1.82; 95% CI 1.19-2.78; p = 0.006) compared with never adding salt. Presented data suggest the possible relationship between additional adding of salt to prepared meals and an increased risk of type 2 diabetes.

Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota

PubMed Central

Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

2016-01-01

Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the developing infant gut microbiome. PMID:27362264

Factors affecting microbial adhesion to stainless steel and other materials used in medical devices.

PubMed

Verran, J; Whitehead, K

2005-11-01

The role of biofilm in medical device associated infections is well documented. Biofilms are more resistant to antibiotics than planktonic cells, these are extremely difficult to treat. Prevention strategies include efforts to insert implants under stringent aseptic conditions, and also encompass the development of novel materials which interfere with the initial attachment of microorganisms to the surface of the device. Microbial cells also attach onto hygienic surfaces in the hospital setting, and thereby pose a cross-infection problem. In this case, vigorous cleaning and sanitizing regimes may be employed in addition to any surface modifications. Many factors affect the initial attachment of organisms to inert substrata, and their subsequent retention or removal/detachment, including the physical and chemical nature and location of the substratum, the type of organic material and microorganisms potentially fouling the surface, and the nature of the interface (solid-liquid in the body; solid-air on environmental surfaces). Focusing on one factor, surface topography, it is apparent that many further variables need to be defined in order to fully understand the interactions occurring between the cell and surface. It is therefore important when modifying one substratum surface property in order to reduce adhesion, to also consider other potentially confounding factors.

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

PubMed

Boy, Erick; Bruce, Nigel; Delgado, Hernán

2002-01-01

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

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

PubMed Central

Boy, Erick; Bruce, Nigel; Delgado, Hernán

2002-01-01

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

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

PubMed

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

2016-09-01

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

Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

PubMed

Wu, Wilfred; Clark, Erin A S; Stoddard, Gregory J; Watkins, W Scott; Esplin, M Sean; Manuck, Tracy A; Xing, Jinchuan; Varner, Michael W; Jorde, Lynn B

2013-04-25

Because of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup analysis by population strata to: (1) reduce the confounding effect of population structure, (2) increase sample size and statistical power, and (3) elucidate the association between rs1800975 and PTB. We reviewed all published papers for PTB phenotype and SNP rs1800795 genotype. Maternal genotype and fetal genotype were analyzed separately and the analyses were stratified by population. The PTB phenotype was defined as gestational age (GA) < 37 weeks, but results from earlier GA were selected when available. All studies were compared by genotype (CC versus CG+GG), based on functional studies.For the maternal genotype analysis, 1,165 PTBs and 3,830 term controls were evaluated. Populations were stratified into women of European descent (for whom the most data were available) and women of heterogeneous origin or admixed populations. All ancestry was self-reported. Women of European descent had a summary odds ratio (OR) of 0.68, (95% confidence interval (CI) 0.51 - 0.91), indicating that the CC genotype is protective against PTB. The result for non-European women was not statistically significant (OR 1.01, 95% CI 0.59 - 1.75). For the fetal genotype analysis, four studies were included; there was no significant association with PTB (OR 0.98, 95% CI 0.72 - 1.33). Sensitivity analysis showed that preterm premature rupture of membrane (PPROM) may be a confounding factor contributing to phenotype heterogeneity. IL6 SNP rs1800795 genotype CC is protective against PTB in women of European descent. It is not significant in other heterogeneous or admixed populations, or in fetal genotype analysis.Population structure is an important confounding factor that should be controlled for in studies of PTB.

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

PubMed

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

2018-05-01

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

Participation in cancer screening among female migrants and non-migrants in Germany

PubMed Central

Brzoska, Patrick; Abdul-Rida, Chadi

2016-01-01

Abstract In many European countries, migrants utilize cancer screening less often than non-migrants. In Germany, in contrast, higher rates of utilization among migrants as compared with non-migrants have been reported. The role of demographic and socioeconomic factors potentially confounding the association between migration status and participation in screening, however, could not be studied. The present study aims to investigate the utilization of cancer screening among migrant and nonmigrant women residing in Germany, adjusting for potential confounders. We used self-reported information from women surveyed on whether they have ever participated in screening for cancer (n = 11,709). The data was collected as part of a cross-sectional representative telephone survey conducted by the Robert Koch-Institute in 2010. We distinguished between three groups of women: (1) respondents of non-German nationality, those who had immigrated to Germany after their birth or those who have two foreign-born parents (“migrants with two-sided migration background”), (2) respondents who only have one foreign-born parent (“migrant with one-sided migration background”), and (3) all others (“non-migrants”). To account for confounders, logistic regression analysis was performed. Only individuals proficient in German were included in the survey, allowing to control for a bias arising from poor language proficiency. 84.9% of nonmigrant women, 82.1% of women with a one-sided, and 70.5% of women with a two-sided migration background had utilized screening for cancer at least once in their lifetime before the survey. The adjusted odds ratios (OR) as compared with nonmigrant women were 0.99 (95% confidence interval [95% CI]: 0.77–1.27) and 0.55 (95% CI: 0.47–0.64), respectively. The study shows that migrant women with a two-sided migration background residing in Germany utilize screening for cancer less often than nonmigrant women—independently of demographic and socioeconomic factors. This is in line with findings from other countries. Likely, barriers that migrant women encounter limit them from taking informed choices. These barriers need to be identified and appropriate measures aiming to enhance informed decision making must be implemented. PMID:27472697

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

PubMed

Aarabi, Ardalan; Osharina, Victoria; Wallois, Fabrice

2017-07-15

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

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

PubMed Central

2013-01-01

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

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

PubMed

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

2013-11-01

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

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

PubMed

Bao, Ai-Min; Swaab, Dick F

2018-01-01

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

Drug induced liver injury with analysis of alternative causes as confounding variables.

PubMed

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.

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

PubMed Central

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

2012-01-01

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

Psychosocial well-being and health-related quality of life in a UK population with Usher syndrome.

PubMed

Dean, Gavin; Orford, Amy; Staines, Roy; McGee, Anna; Smith, Kimberley J

2017-01-12

To determine whether psychosocial well-being is associated with the health-related quality of life (HRQOL) of people with Usher syndrome. The survey was advertised online and through deafblind-related charities, support groups and social groups throughout the UK. 90 people with Usher syndrome took part in the survey. Inclusion criteria are having a diagnosis of Usher syndrome, being 18 or older and being a UK resident. All participants took part in a survey that measured depressive symptoms, loneliness and social support (predictors) and their physical and mental HRQOL (outcomes). Measured confounders included age-related, sex-related and health-related characteristics. Hierarchical multiple linear regression analyses examined the association of each psychosocial well-being predictor with the physical and mental HRQOL outcomes while controlling for confounders in a stepwise manner. After adjusting for all confounders, psychosocial well-being was shown to predict physical and mental HRQOL in our population with Usher syndrome. Increasing depressive symptoms were predictive of poorer physical (β=-0.36, p<0.01) and mental (β=-0.60, p<0.001) HRQOL. Higher levels of loneliness predicted poorer mental HRQOL (β=-0.20, p<0.05). Finally, increasing levels of social support predicted better mental HRQOL (β=0.19, p<0.05). Depression, loneliness and social support all represent important issues that are linked with HRQOL in a UK population with Usher syndrome. Our results add to the growing body of evidence that psychosocial well-being is an important factor to consider in people with Usher syndrome alongside functional and physical impairment within research and clinical practice. 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/.

Cancer incidence in Holocaust male survivors-An Israeli cohort study.

PubMed

Keinan-Boker, Lital; Goldbourt, Uri

2016-12-01

Previous studies, often using proxy exposure assessment and not controlling for individual risk factors, suggested higher cancer risk in Holocaust survivors. We have used individual-level data from a male cohort of Israeli civil servants recruited in 1963 to investigate cancer incidence in Holocaust survivors, controlling for potential confounders. The analysis included 4,669 Europe-born subjects; 689 exposed = E (immigrated to Israel after 1939 and reported of being in Nazi camps during World War II); 2,307 potentially exposed = PE (immigrated to Israel after 1939 and reported of not being in Nazi camps); and 1,673 non-exposed = NE (immigrated to Israel prior to 1939). Vital status and cancer incidence in the cohort were determined based on national registries. Socioeconomic level, health behaviors and cancer incidence were compared between the groups and Cox proportional hazards regression models adjusting for potential confounders assessed hazard risk ratios for cancer by exposure status. All-cause mortality was studied as a competing risk. In total, 241, 682, and 522 cancer cases were diagnosed in the E, PE, and NE, respectively. Compared with the NE, all-site cancer incidence was higher in the E (HR = 1.13, 95%CI 0.97-1.32) but not in the PE. All-cause mortality competed with all-site invasive cancer incidence in the E group (HR = 1.18, 95%CI 1.02-1.38). Colorectal and lung cancer seemed to be positively though non-significantly associated with the exposure while prostate cancer was not. Male Holocaust survivors may be at a weakly increased risk for all-site, colorectal and lung cancer. The role of age at exposure and residual confounding should be further investigated. © 2016 UICC.

A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure Is Defined as Progression to >45 Degrees.

PubMed

Bohl, Daniel D; Telles, Connor J; Ruiz, Ferrin K; Badrinath, Raghav; DeLuca, Peter A; Grauer, Jonathan N

2016-04-01

Retrospective cohort. To determine whether a genetic test is associated with successful Providence bracing for adolescent idiopathic scoliosis (AIS). Genetic factors have been defined that predict the risk of progression of AIS in a polygenic fashion. From these data, a commercially available genetic test, ScoliScore, was developed. It is now used in clinical practice for counseling and to guide clinical management. Bracing is a mainstay of treatment for AIS. Large efforts have been made recently to reduce potential confounding across studies of different braces; however, none of these have considered genetics as a potential confounder. In particular, ScoliScore has not been evaluated in a population undergoing bracing. We conducted a retrospective cohort study in which we identified a population of AIS patients who were initiated with Providence bracing and followed over time. Although these patients did not necessarily fit the commercial indications for ScoliScore, we contacted the patients and obtained a saliva sample from each for genetic analysis. We then tested whether ScoliScore correlated with the outcome of their bracing therapy. We were able to contact and invite 25 eligible subjects, of whom 16 (64.0%) returned samples for laboratory analysis. Patients were followed for an average of 2.3 years (range, 1.1-4 y) after initiation of the Providence brace. Eight patients (50.0%) progressed to >45 degrees, whereas the other 8 patients (50.0%) did not. The mean ScoliScore among those who progressed to >45 degrees was higher than that among those who did not (176 vs. 112, P=0.030). We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding.

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

PubMed

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

2003-01-01

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

Psychosocial well-being and health-related quality of life in a UK population with Usher syndrome

PubMed Central

Dean, Gavin; Orford, Amy; Staines, Roy; McGee, Anna; Smith, Kimberley J

2017-01-01

Objectives To determine whether psychosocial well-being is associated with the health-related quality of life (HRQOL) of people with Usher syndrome. Setting The survey was advertised online and through deafblind-related charities, support groups and social groups throughout the UK. Participants 90 people with Usher syndrome took part in the survey. Inclusion criteria are having a diagnosis of Usher syndrome, being 18 or older and being a UK resident. Primary and secondary outcome measures All participants took part in a survey that measured depressive symptoms, loneliness and social support (predictors) and their physical and mental HRQOL (outcomes). Measured confounders included age-related, sex-related and health-related characteristics. Hierarchical multiple linear regression analyses examined the association of each psychosocial well-being predictor with the physical and mental HRQOL outcomes while controlling for confounders in a stepwise manner. Results After adjusting for all confounders, psychosocial well-being was shown to predict physical and mental HRQOL in our population with Usher syndrome. Increasing depressive symptoms were predictive of poorer physical (β=−0.36, p<0.01) and mental (β=−0.60, p<0.001) HRQOL. Higher levels of loneliness predicted poorer mental HRQOL (β=−0.20, p<0.05). Finally, increasing levels of social support predicted better mental HRQOL (β=0.19, p<0.05). Conclusions Depression, loneliness and social support all represent important issues that are linked with HRQOL in a UK population with Usher syndrome. Our results add to the growing body of evidence that psychosocial well-being is an important factor to consider in people with Usher syndrome alongside functional and physical impairment within research and clinical practice. PMID:28082366

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

PubMed

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

2017-06-05

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2015-07-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2008-06-01

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

What's in a name? Y chromosomes, surnames and the genetic genealogy revolution.

PubMed

King, Turi E; Jobling, Mark A

2009-08-01

Heritable surnames are highly diverse cultural markers of coancestry in human populations. A patrilineal surname is inherited in the same way as the non-recombining region of the Y chromosome and there should, therefore, be a correlation between the two. Studies of Y haplotypes within surnames, mostly of the British Isles, reveal high levels of coancestry among surname cohorts and the influence of confounding factors, including multiple founders for names, non-paternities and genetic drift. Combining molecular genetics and surname analysis illuminates population structure and history, has potential applications in forensic studies and, in the form of 'genetic genealogy', is an area of rapidly growing interest for the public.

HIV Genetic Diversity and Drug Resistance.

PubMed

Santos, André F; Soares, Marcelo A

2010-02-01

Most of the current knowledge on antiretroviral (ARV) drug development and resistance is based on the study of subtype B of HIV-1, which only accounts for 10% of the worldwide HIV infections. Cumulative evidence has emerged that different HIV types, groups and subtypes harbor distinct biological properties, including the response and susceptibility to ARV. Recent laboratory and clinical data highlighting such disparities are summarized in this review. Variations in drug susceptibility, in the emergence and selection of specific drug resistance mutations, in viral replicative capacity and in the dynamics of resistance acquisition under ARV selective pressure are discussed. Clinical responses to ARV therapy and associated confounding factors are also analyzed in the context of infections by distinct HIV genetic variants.

Can we continue to ignore gender differences in performance on simulation trainers?

PubMed

Thorson, Chad M; Kelly, Jason P; Forse, R Armour; Turaga, Kiran K

2011-05-01

There are differences between the genders in their innate performances on simulation trainers, which may impair accurate assessment of psychomotor skills. The performance of fourth-year students with no exposure to the Minimally Invasive Surgical Trainer compared based on gender, and other psychomotor skills. Our study included 16 male and 16 female students. After adjusting for choice of medical specialty (P<.001), current video game use (P=.6), and experience in the operating room (P=.4), female sex was an independent factor for worse performance (P=.04) in multivariate models. Women took more time than men (P<.01) and made more errors (29 versus 25 on 3 reps, P<.01). Among medical students with no previous exposure to laparoscopic trainers, female students perform worse than male students after adjusting for confounding factors. This difference must be recognized by training programs while using simulators for training and evaluation.

The significance of cell-related challenges in the clinical application of tissue engineering.

PubMed

Almela, Thafar; Brook, Ian M; Moharamzadeh, Keyvan

2016-12-01

Tissue engineering is increasingly being recognized as a new approach that could alleviate the burden of tissue damage currently managed with transplants or synthetic devices. Making this novel approach available in the future for patients who would potentially benefit is largely dependent on understanding and addressing all those factors that impede the translation of this technology to the clinic. Cell-associated factors in particular raise many challenges, including those related to cell sources, up- and downstream techniques, preservation, and the creation of in vitro microenvironments that enable cells to grow and function as far as possible as they would in vivo. This article highlights the main confounding issues associated with cells in tissue engineering and how these issues may hinder the advancement of therapeutic tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3157-3163, 2016. © 2016 Wiley Periodicals, Inc.

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

PubMed Central

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

2003-01-01

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

Cancer prevalence and education by cancer site: logistic regression analysis.

PubMed

Johnson, Stephanie; Corsten, Martin J; McDonald, James T; Gupta, Michael

2010-10-01

Previously, using the American National Health Interview Survey (NHIS) and a logistic regression analysis, we found that upper aerodigestive tract (UADT) cancer is correlated with low socioeconomic status (SES). The objective of this study was to determine if this correlation between low SES and cancer prevalence exists for other cancers. We again used the NHIS and employed education level as our main measure of SES. We controlled for potentially confounding factors, including smoking status and alcohol consumption. We found that only two cancer subsites shared the pattern of increased prevalence with low education level and decreased prevalence with high education level: UADT cancer and cervical cancer. UADT cancer and cervical cancer were the only two cancers identified that had a link between prevalence and lower education level. This raises the possibility that an associated risk factor for the two cancers is causing the relationship between lower education level and prevalence.

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

PubMed

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

2017-03-01

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

HOMA-IR Values are Associated With Glycemic Control in Japanese Subjects Without Diabetes or Obesity: The KOBE Study.

PubMed

Hirata, Takumi; Higashiyama, Aya; Kubota, Yoshimi; Nishimura, Kunihiro; Sugiyama, Daisuke; Kadota, Aya; Nishida, Yoko; Imano, Hironori; Nishikawa, Tomofumi; Miyamatsu, Naomi; Miyamoto, Yoshihiro; Okamura, Tomonori

2015-01-01

Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men. HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

Emerging technologies in bioremediation: constraints and opportunities.

PubMed

Rayu, Smriti; Karpouzas, Dimitrios G; Singh, Brajesh K

2012-11-01

Intensive industrialisation, inadequate disposal, large-scale manufacturing activities and leaks of organic compounds have resulted in long-term persistent sources of contamination of soil and groundwater. This is a major environmental, policy and health issue because of adverse effects of contaminants on humans and ecosystems. Current technologies for remediation of contaminated sites include chemical and physical remediation, incineration and bioremediation. With recent advancements, bioremediation offers an environmentally friendly, economically viable and socially acceptable option to remove contaminants from the environment. Three main approaches of bioremediation include use of microbes, plants and enzymatic remediation. All three approaches have been used with some success but are limited by various confounding factors. In this paper, we provide a brief overview on the approaches, their limitations and highlights emerging technologies that have potential to revolutionise the enzymatic and plant-based bioremediation approaches.

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

PubMed

Woolgar, Alexandra; Golland, Polina; Bode, Stefan

2014-09-01

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

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

PubMed Central

2017-01-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2014-01-01

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

Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

PubMed Central

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

2011-01-01

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

Maternal postpartum depressive symptoms and infant externalizing and internalizing behaviors.

PubMed

Vafai, Yassaman; Steinberg, Julia R; Shenassa, Edmond D

2016-02-01

Maternal postpartum depression has been shown to be one of the main predictors of externalizing and internalizing behaviors in toddlers and adolescents. Research suggests that presence of such behaviors can be observed as early as infancy. The current study uses longitudinal data from 247 mothers to examine the relationship between postpartum depressive symptoms at 8 weeks and the infant's externalizing and internalizing behaviors at 12 months. In unadjusted linear regression models, there were associations between postpartum depressive symptoms and infant externalizing behaviors (β=0.082, SE=0.032, p=0.012) and internalizing behaviors (β=0.111, SE=0.037, p=0.003). After controlling for potential confounding factors, including maternal age, race, education, home ownership, smoking status in the postpartum period, marital status, parenting stress, and happiness from becoming a parent, the associations between postpartum depressive symptoms and infant externalizing (β=0.051, SE=0.034, p=0.138) and internalizing behaviors (β=0.077, SE=0.040, p=0.057) were reduced and became non-significant. Furthermore, in these models the total amount of variance explained was 17.2% (p<0.0001) for externalizing behaviors and 10.5% (p<0.01) for internalizing behaviors; the only significant predictor of externalizing behaviors was maternal age (β=-0.074, SE=0.030, p=0.014), and of internalizing behaviors was white non-Hispanic ethnicity (β=-1.33, SE=0.378, p=0.0005). A combined effect of the confounding factors seems to explain the finding of no significant independent association between postpartum depressive symptoms and infant externalizing and internalizing behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Bisphenol A and Peripheral Arterial Disease: Results from the NHANES

PubMed Central

Teppala, Srinivas; Sabanayagam, Charumathi

2012-01-01

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

Influenza vaccination of Michigan children by provider type, 2010-2011.

PubMed

Clayton, Joshua L; Potter, Rachel C; Wells, Eden V; Carlton, Cristi A; Boulton, Matthew L

2014-07-01

Influenza vaccination for all children aged 6 months to 18 years has been recommended since 2008 to prevent flu-related morbidity and mortality. However, 2010-2011 influenza vaccine coverage estimates show under-vaccination in children of all ages. We examined predictors of influenza vaccination in Michigan during the 2010-2011 influenza season. To determine whether immunization provider type was associated with a child's influenza vaccination in Michigan and assess whether county-level factors were confounders of the association. Influenza vaccinations reported to the Michigan Care Improvement Registry from the 2010-2011 influenza season were analyzed in 2012 to estimate ORs for the association between immunization provider type and influenza vaccination. Among 2,373,826 Michigan children aged 6 months through 17 years, 17% were vaccinated against influenza and lower vaccination rates were observed for public compared to private providers (13% vs 18%). In the unadjusted model, public providers had lower odds of vaccinating children compared to private providers (OR=0.60, 95% CI=0.60, 0.61). County-level factors, including percentage of families living below the poverty line, median household income, and percentage black race, were not shown to confound the association. In the adjusted models, public providers had lower odds of vaccinating children compared to private providers (OR=0.87, 95% CI=0.86, 0.88). Although a child's likelihood of influenza vaccination in Michigan varies by provider type, more effective strategies to improve influenza vaccination rates for all Michigan children are needed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

PubMed

Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

2016-04-01

Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Adolescent adaptive behavior profiles in Williams-Beuren syndrome, Down syndrome, and autism spectrum disorder.

PubMed

Del Cole, Carolina Grego; Caetano, Sheila Cavalcante; Ribeiro, Wagner; Kümmer, Arthur Melo E E; Jackowski, Andrea Parolin

2017-01-01

Adaptive behavior can be impaired in different neurodevelopmental disorders and may be influenced by confounding factors, such as intelligence quotient (IQ) and socioeconomic classification. Our main objective was to verify whether adaptive behavior profiles differ in three conditions-Williams Beuren syndrome (WBS), Down syndrome (DS), and autism spectrum disorder (ASD), as compared with healthy controls (HC) and with each other. Although the literature points towards each disorder having a characteristic profile, no study has compared profiles to establish the specificity of each one. A secondary objective was to explore potential interactions between the conditions and socioeconomic status, and whether this had any effect on adaptive behavior profiles. One hundred and five adolescents were included in the study. All adolescents underwent the following evaluations: the Vineland Adaptive Behavior Scale (VABS), the Wechsler Intelligence Scale for Children (WISC), and the Brazilian Economic Classification Criteria. Our results demonstrated that the WBS group performed better than the DS group in the communication domain, β = -15.08, t(3.45), p = .005, and better than the ASD group in the socialization domain, β = 8.92, t(-2.08), p = .013. The DS group also performed better than the ASD group in socialization, β = 16.98, t(-2.32), p = .024. IQ was an important confounding factor, and socioeconomic status had an important effect on the adaptive behavior of all groups. There is a heterogeneity regarding adaptive behavior profiles in WBS, DS, and ASD. These data are important to better design specific strategies related to the health and social care of each particular group.

Urine specific gravity as an indicator of dehydration in Olympic combat sport athletes; considerations for research and practice.

PubMed

Zubac, Damir; Reale, Reid; Karnincic, Hrvoje; Sivric, Anamaria; Jelaska, Igor

2018-05-10

Urine specific gravity (U SG ) is the most commonly reported biochemical marker used in research and applied settings to detect fluid deficits in athletes, including those participating in combat sports. Despite the popularity of its use, there has been a growing debate regarding the diagnostic accuracy and the applicability of U SG in characterizing whole-body fluid status and fluctuations. Moreover, recent investigations report universally high prevalence of hypohydration (∼90%) via U SG assessment in combat sport athletes, often in spite of stable body-mass. Given the widespread use in both research and practice, and its use in a regulatory sense as a 'hydration test' in combat sports as a means to detect dehydration at the time of weigh-in; understanding the limitations and applicability of U SG assessment is of paramount importance. Inconsistencies in findings of U SG readings, possibly as a consequence of diverse methodological research approaches and/or overlooked confounding factors, preclude a conclusive position stand within current combat sports research and practice. Thus the primary aim of this paper is to critically review the literature regarding U SG assessment of hydration status in combat sports research and practice. When taken on balance, the existing literature suggests: the use of laboratory derived benchmarks in applied settings, inconsistent sampling methodologies, the incomplete picture of how various confounding factors affect end-point readings, and the still poorly understood potential of renal adaptation to dehydration in combat athletes; make the utility of hydration assessment via U SG measurement quite problematic, particularly when diet and training is not controlled.

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

PubMed

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

2018-01-01

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

Comorbidity of intellectual disability confounds ascertainment of autism: implications for genetic diagnosis.

PubMed

Polyak, Andrew; Kubina, Richard M; Girirajan, Santhosh

2015-10-01

While recent studies suggest a converging role for genetic factors towards risk for nosologically distinct disorders including autism, intellectual disability (ID), and epilepsy, current estimates of autism prevalence fail to take into account the impact of comorbidity of these disorders on autism diagnosis. We aimed to assess the effect of comorbidity on the diagnosis and prevalence of autism by analyzing 11 years (2000-2010) of special education enrollment data on approximately 6.2 million children per year. We found a 331% increase in the prevalence of autism from 2000 to 2010 within special education, potentially due to a diagnostic recategorization from frequently comorbid features such as ID. The decrease in ID prevalence equaled an average of 64.2% of the increase of autism prevalence for children aged 3-18 years. The proportion of ID cases potentially undergoing recategorization to autism was higher (P = 0.007) among older children (75%) than younger children (48%). Some US states showed significant negative correlations between the prevalence of autism compared to that of ID while others did not, suggesting state-specific health policy to be a major factor in categorizing autism. Further, a high frequency of autistic features was observed when individuals with classically defined genetic syndromes were evaluated for autism using standardized instruments. Our results suggest that current ascertainment practices are based on a single facet of autism-specific clinical features and do not consider associated comorbidities that may confound diagnosis. Longitudinal studies with detailed phenotyping and deep molecular genetic analyses are necessary to completely understand the cause of this complex disorder. © 2015 Wiley Periodicals, Inc.

Associations between cognitive biases and domains of schizotypy in a non-clinical sample.

PubMed

Aldebot Sacks, Stephanie; Weisman de Mamani, Amy Gina; Garcia, Cristina Phoenix

2012-03-30

Schizotypy is a non-clinical manifestation of the same underlying biological factors that give rise to psychotic disorders (Claridge and Beech, 1995). Research on normative populations scoring high on schizotypy is valuable because it may help elucidate the predisposition to schizophrenia (Jahshan and Sergi, 2007) and because performance is not confounded by issues present in schizophrenia samples. In the current study, a Confirmatory Factor Analysis was conducted using several comprehensive measures of schizotypy. As expected and replicating prior research, a four-factor model of schizotypy emerged including a positive, a negative, a cognitive disorganization, and an impulsive nonconformity factor. We also evaluated how each factor related to distinct cognitive biases. In support of hypotheses, increased self-certainty, decreased theory of mind, and decreased source memory were associated with higher scores on the positive factor; decreased theory of mind was associated with higher scores on the negative factor; and increased self-certainty was associated with greater impulsive nonconformity. Unexpectedly, decreased self-certainty and increased theory of mind were associated with greater cognitive disorganization, and decreased source memory was associated with greater impulsive nonconformity. These findings offer new insights by highlighting cognitive biases that may be risk factors for psychosis. Published by Elsevier Ireland Ltd.

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

PubMed Central

2012-01-01

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

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

PubMed

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

2009-06-08

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

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

PubMed

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

2012-11-02

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-01

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

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

PubMed

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

2016-09-01

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

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

PubMed

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

2018-02-01

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

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

PubMed

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

2011-12-01

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

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

PubMed

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

2013-06-01

Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients <45 years of age to 26.1% in patients aged ≥85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with β-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies.

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

PubMed

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

2018-03-15

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

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

PubMed

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

2012-10-01

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

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

PubMed

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

2014-12-01

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

Photosynthetic responses to temperature across leaf-canopy-ecosystem scales: a 15-year study in a Californian oak-grass savanna.

PubMed

Ma, Siyan; Osuna, Jessica L; Verfaillie, Joseph; Baldocchi, Dennis D

2017-06-01

Ecosystem CO 2 fluxes measured with eddy-covariance techniques provide a new opportunity to retest functional responses of photosynthesis to abiotic factors at the ecosystem level, but examining the effects of one factor (e.g., temperature) on photosynthesis remains a challenge as other factors may confound under circumstances of natural experiments. In this study, we developed a data mining framework to analyze a set of ecosystem CO 2 fluxes measured from three eddy-covariance towers, plus a suite of abiotic variables (e.g., temperature, solar radiation, air, and soil moisture) measured simultaneously, in a Californian oak-grass savanna from 2000 to 2015. Natural covariations of temperature and other factors caused remarkable confounding effects in two particular conditions: lower light intensity at lower temperatures and drier air and soil at higher temperatures. But such confounding effects may cancel out. At the ecosystem level, photosynthetic responses to temperature did follow a quadratic function on average. The optimum value of photosynthesis occurred within a narrow temperature range (i.e., optimum temperature, T opt ): 20.6 ± 0.6, 18.5 ± 0.7, 19.2 ± 0.5, and 19.0 ± 0.6 °C for the oak canopy, understory grassland, entire savanna, and open grassland, respectively. This paradigm confirms that photosynthesis response to ambient temperature changes is a functional relationship consistent across leaf-canopy-ecosystem scales. Nevertheless, T opt can shift with variations in light intensity, air dryness, or soil moisture. These findings will pave the way to a direct determination of thermal optima and limits of ecosystem photosynthesis, which can in turn provide a rich resource for baseline thresholds and dynamic response functions required for predicting global carbon balance and geographic shifts of vegetative communities in response to climate change.

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

PubMed

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

2013-01-01

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

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

PubMed

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

2005-07-01

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

Open-Ended Coaxial Probe Technique for Dielectric Measurement of Biological Tissues: Challenges and Common Practices.

PubMed

La Gioia, Alessandra; Porter, Emily; Merunka, Ilja; Shahzad, Atif; Salahuddin, Saqib; Jones, Marggie; O'Halloran, Martin

2018-06-05

Electromagnetic (EM) medical technologies are rapidly expanding worldwide for both diagnostics and therapeutics. As these technologies are low-cost and minimally invasive, they have been the focus of significant research efforts in recent years. Such technologies are often based on the assumption that there is a contrast in the dielectric properties of different tissue types or that the properties of particular tissues fall within a defined range. Thus, accurate knowledge of the dielectric properties of biological tissues is fundamental to EM medical technologies. Over the past decades, numerous studies were conducted to expand the dielectric repository of biological tissues. However, dielectric data is not yet available for every tissue type and at every temperature and frequency. For this reason, dielectric measurements may be performed by researchers who are not specialists in the acquisition of tissue dielectric properties. To this end, this paper reviews the tissue dielectric measurement process performed with an open-ended coaxial probe. Given the high number of factors, including equipment- and tissue-related confounders, that can increase the measurement uncertainty or introduce errors into the tissue dielectric data, this work discusses each step of the coaxial probe measurement procedure, highlighting common practices, challenges, and techniques for controlling and compensating for confounders.

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

PubMed

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

2016-01-01

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

Sarcopenia is a risk factor for elevated aminotransferase in men independently of body mass index, dietary habits, and physical activity.

PubMed

Yoo, Ki Deok; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon

2015-04-01

Aminotransferase activity is a surrogate marker of liver injury showing strong correlations with obesity and metabolic syndrome. However, elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic patients in clinical practice. To examine the relationship between sarcopenia and aminotransferase activity in a large population-based cohort. Data from the Korean National Health and Nutrition Examinations were used. A total of 13,431 subjects were included. A whole-body dual X-ray absorptiometry scan was performed on each patient to measure total and regional muscle mass. Appendicular skeletal muscle mass indices were also obtained. The prevalence of sarcopenia was significantly higher in the group with elevated aminotransferase levels than in the normal liver enzyme group (males: 26.5% vs. 16.9%; females: 38.3% vs. 22.1%, p<0.05). The skeletal muscle index was negatively correlated with most cardiometabolic risk factors, including fasting glucose and cholesterol levels. The frequency of elevated aminotransferase increased in male patients with sarcopenia after adjusting for potential confounding factors including age, body mass index, fasting glucose level, dietary, and exercise habits. However, the correlation was no longer observed in women after adjusting for body mass index. Sarcopenia is a risk factor for elevated aminotransferase in men, independently of body mass index, dietary habits, and physical activity. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study.

PubMed

de Keyser, Catherine E; Leening, Maarten J G; Romio, Silvana A; Jukema, J Wouter; Hofman, Albert; Ikram, M Arfan; Franco, Oscar H; Stijnen, Theo; Stricker, Bruno H

2014-11-01

When studying the causal effect of drug use in observational data, marginal structural modeling (MSM) can be used to adjust for time-dependent confounders that are affected by previous treatment. The objective of this study was to compare traditional Cox proportional hazard models (with and without time-dependent covariates) with MSM to study causal effects of time-dependent drug use. The example of primary prevention of cardiovascular disease (CVD) with statins was examined using up to 17.7 years of follow-up from 4,654 participants of the observational prospective population-based Rotterdam Study. In the MSM model, the weight was based on measurements of established cardiovascular risk factors and co-morbidity. In general, we could not demonstrate important differences in results from the Cox models and MSM. Results from analysis on duration of statin use suggested that substantial residual confounding by indication was not accounted for during the period shortly after statin initiation. In conclusion, although on theoretical grounds MSM is an elegant technique, lack of data on the precise time-dependent confounders, such as indication of treatment or other considerations of the prescribing physician jeopardizes the calculation of valid weights. Confounding remains a hurdle in observational effectiveness research on preventive drugs with a multitude of prescription determinants.

Relationship of family formation characteristics with unsafe abortion: is it confounded by women's socio-economic status? - A case-control study from Sri Lanka.

PubMed

Arambepola, Carukshi; Rajapaksa, Lalini C; Attygalle, Deepika; Moonasinghe, Loshan

2016-06-17

Literature shows that choice for unsafe abortion is often driven by poverty. However, factors related to the family formation behaviour of women are also implied as determinants of this decision. This study assessed which family formation characteristics of women are associated with the risk of unsafe abortion, without being confounded by their low socio-economic status among Sri Lankan women admitted to hospital following post-abortion complications. An unmatched case-control study was conducted in nine hospitals in eight districts in Sri Lanka among 171 women with post-abortion complications following unsafe abortion (Cases) and 600 postpartum mothers admitted to same hospitals during the same period for delivery of term unintended pregnancies (Controls). Interviewer-administered-questionnaires obtained demographic, socio-economic and family formation related characteristics. Risk factors of abortion were assessed by odds-ratio (OR), adjusted for their socio-economic status in logistic regression analysis. Low socio-economic status, characterised by low-education (adjusted OR = 1.5; 95 % CI = 1.1-2.4) and less/unskilled occupations (2.3; 1.4-3.6) was a significant risk factor for unsafe abortion. Independent of this risk, being unmarried (9.3; 4.0-21.6), failure in informed decisions about desired family size (2.2; 1.4-3.5), not having a girl-child (2.2; 1.4-3.4) and longer average birth intervals (0.7 years; 0.6-0.8) signified the vulnerability of women for unsafe abortion. Cases were as fast as the controls in their family completion (4.3 versus 4.5 years; p = 0.4), but were at increased risk for abortion, if their average birth intervals (including the last one) were longer. Previous contraceptive use, age at reproductive events or partners' characteristics did not impart any risk for abortion. Low socio-economic status is not the most influencing risk factor for unsafe abortions leading to complications, but many other factors in relation to their family formation characteristics that are independent of their low socio-economic status.

Testing the Developmental Origins of Health and Disease Hypothesis for Psychopathology Using Family-Based Quasi-Experimental Designs

PubMed Central

D’Onofrio, Brian M.; Class, Quetzal A.; Lahey, Benjamin B.; Larsson, Henrik

2014-01-01

The Developmental Origin of Health and Disease (DOHaD) hypothesis is a broad theoretical framework that emphasizes how early risk factors have a causal influence on psychopathology. Researchers have raised concerns about the causal interpretation of statistical associations between early risk factors and later psychopathology because most existing studies have been unable to rule out the possibility of environmental and genetic confounding. In this paper we illustrate how family-based quasi-experimental designs can test the DOHaD hypothesis by ruling out alternative hypotheses. We review the logic underlying sibling-comparison, co-twin control, offspring of siblings/twins, adoption, and in vitro fertilization designs. We then present results from studies using these designs focused on broad indices of fetal development (low birth weight and gestational age) and a particular teratogen, smoking during pregnancy. The results provide mixed support for the DOHaD hypothesis for psychopathology, illustrating the critical need to use design features that rule out unmeasured confounding. PMID:25364377

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-11-01

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

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

PubMed

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

2016-10-12

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

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

PubMed

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

2015-11-01

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

Psychosocial working conditions and exhaustion in a working population sample of Swedish middle-aged men and women.

PubMed

Lindeberg, Sara I; Rosvall, Maria; Choi, Bongkyoo; Canivet, Catarina; Isacsson, Sven-Olof; Karasek, Robert; Ostergren, Per-Olof

2011-04-01

Exhaustion is a concept of interest for both occupational health research and stress-disease theory research. The aim of the present study was to explore associations between chronic stressors, in terms of psychosocial working conditions, and exhaustion in a Swedish middle-aged population sample. A vocationally active population sample of the Malmö Shoulder and Neck Study cohort, comprising 2555 men and 2466 women between 45 and 64 years of age, was used. Psychosocial working conditions, assessed by means of the demand-control-support model, were measured longitudinally with a 1-year interval. Exhaustion was assessed by the SF-36 vitality scale and measured at follow-up, yielding a cross-sectional study design. Exhaustion was twice as common in women as in men. High psychological job demands, low job control and low job support were independently associated with exhaustion in both men and women. These associations remained after controlling for a variety of potential confounders and mediators, including socio-demographic factors, lifestyle factors, musculoskeletal pain, disease, other work-related factors (including physical workload) and non-work-related factors. High demands in combination with low control (job strain), and job strain combined with low job support (iso-strain), increased the risk for exhaustion. Psychosocial working conditions seem to contribute to exhaustion in middle-aged men and women. Future research should include exploration of exhaustion as a possible mediator between work stress and disease, as well as exploration of other chronic stressors, including non-work-related stressors, regarding their effects on exhaustion in men and women.

Disease features and outcomes in United States lupus patients of Hispanic origin and their Mestizo counterparts in Latin America: a commentary

PubMed Central

Pons-Estel, Guillermo J.; Molineros, Julio; Wojdyla, Daniel; McGwin, Gerald; Nath, Swapan K.; Pons-Estel, Bernardo A.; Alarcón-Riquelme, Marta; Alarcón, Graciela S.

2016-01-01

Objective. To evaluate disease features and outcomes in two populations with significant Amerindian ancestry. Methods. Hispanic patients (from Texas) from the Lupus in Minorities: Nature versus Nurture (LUMINA) cohort and Mestizo patients from the Grupo Latino Americano De Estudio del Lupus or Latin American Group for the Study of Lupus (GLADEL) cohort were included. Disease features and outcomes were evaluated at baseline and last visit. Admixture informative markers of Mestizo Genoma de Lupus Eritematoso Sistémico Network consortium (GENLES) patients and Hispanic LUMINA patients were compared. Univariable analyses were performed using Chi square or Student’s t test as appropriate. Multivariable analyses adjusting for possible confounders were carried out using Poisson, logistic or Cox regression models as appropriate. Results. A total of 114 LUMINA and 619 GLADEL patients were included. GLADEL patients had accrued more damage at baseline, but the opposite was the case at last visit. Being from LUMINA was a risk factor for damage accrual, even after adjusting for possible confounders [relative risk (RR) 1.33, 95% CI 1.12, 1.58]. Also, LUMINA patients have a higher risk of mortality than GLADEL patients [hazard ratio (HR) 2.37, 95% CI 1.10, 5.15], having 5-year survival of 85.6% and 94.5%, respectively. In addition, 79 LUMINA patients and 744 Mestizo GENLES patients were evaluated in order to compare genetic ancestry between the two groups; GENLES patients had a higher proportion of European ancestry (48.5% vs 43.3%, P = 0.003) and a lower proportion of Asian ancestry (3.7% vs 4.9%, P = 0.048), but the proportions of Amerindian and African ancestry were comparable in both. Conclusion. USA Hispanic patients seemed to have a poorer prognosis than their counterparts from Latin America, despite having a comparable genetic background. Socioeconomic factors may account for these observations. PMID:26412809

Radiographic bone loss in a Scottish non-smoking Type 1 Diabetes mellitus population; a Bitewing Radiographic Study.

PubMed

Plessas, Anastasios; Robertson, Douglas P; Hodge, Penny J

2018-05-15

The dental complications of uncontrolled diabetes include reduced salivary flow rate, candidiasis and periodontal manifestations. A recent meta-analysis concluded that diabetes patients have a significantly higher severity, but not extent, of destructive periodontal disease than non-diabetes people. The authors reported that most type-1 diabetes studies using dental radiographic data have not controlled for confounding factors such as smoking. The aim of this cross-sectional study was to compare radiographic alveolar bone loss between type 1 diabetes (T1DM) and non-diabetes (NDM) participants in a Scottish non-smoking population. Digital bitewing radiographs for 174 Scottish adult never or ex-smoker (> 5 years) participants (108 T1DM, 66 NDS), recruited from outpatient clinics throughout Greater Glasgow and Clyde, were included in the analysis. A single blinded, trained and calibrated examiner recorded the radiographic bone loss seen on bitewing radiographs using the digital screen caliper. The bone loss was measured as the distance between the cemento-enamel junction (CEJ) and the deepest radiographic alveolar bone margin interproximally of each tooth. T1DM participants had more radiographic alveolar bone loss throughout the all teeth measured (median:1.27 mm vs 1.06 mm, P < 0.001) and more than a two fold increase in the risk of having sites with ≥2 mm periodontal destruction (OR = 2.297, 95%CI 1.058-4.986, P = 0.036) compared with non-diabetes subjects. Patients suffering from type 1 diabetes are at higher risk of periodontitis even when controlling for multiple possible confounding factors and this difference can be detected on routine dental radiographs at an early stage. These data confirm radiographically the previously reported association between T1DM and periodontal bone loss. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women’s Survey

PubMed Central

Harvey, Nicholas C.; Moon, Rebecca J.; Sayer, Avan Aihie; Ntani, Georgia; Davies, Justin H.; Javaid, M Kassim; Robinson, Sian M.; Godfrey, Keith M.; Inskip, Hazel M.; Cooper, Cyrus

2013-01-01

Context Maternal 25-hydroxy-vitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function but little is known about a role for antenatal 25(OH)D exposure in programming muscle development. Objective We investigated the associations between maternal plasma 25(OH)D status at 34 weeks gestation and offspring lean mass and muscle strength at 4 years of age. Design and setting A prospective UK population-based mother-offspring cohort: the Southampton Women’s Survey (SWS). Participants 12583 non-pregnant women were initially recruited into SWS, of which 3159 had singleton pregnancies. 678 mother-child pairs were included in this analysis. Main Outcomes Measured At 4 years of age, offspring assessments included hand grip strength (Jamar Dynamometer) and whole body DXA (Hologic Discovery) yielding lean mass and %lean mass. Physical activity was assessed by 7-day accelerometry (Actiheart) in a subset of children (n=326). Results Maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength (β=0.10 SD/SD, p=0.013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding and child’s physical activity at 4 years (β=0.13 SD/SD, p=0.014). Maternal 25(OH)D was also positively associated with offspring %lean mass (β=0.11 SD/SD, p=0.006), but not total lean mass (β=0.06, p=0.15). This however did not persist after adjustment for confounding factors (β=0.09 SD/SD, p=0.11). Conclusions This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than muscle mass. PMID:24178796

The effect of alcohol advertising, marketing and portrayal on drinking behaviour in young people: systematic review of prospective cohort studies.

PubMed

Smith, Lesley A; Foxcroft, David R

2009-02-06

The effect of alcohol portrayals and advertising on the drinking behaviour of young people is a matter of much debate. We evaluated the relationship between exposure to alcohol advertising, marketing and portrayal on subsequent drinking behaviour in young people by systematic review of cohort (longitudinal) studies. studies were identified in October 2006 by searches of electronic databases, with no date restriction, supplemented with hand searches of reference lists of retrieved articles. Cohort studies that evaluated exposure to advertising or marketing or alcohol portrayals and drinking at baseline and assessed drinking behaviour at follow-up in young people were selected and reviewed. seven cohort studies that followed up more than 13,000 young people aged 10 to 26 years old were reviewed. The studies evaluated a range of different alcohol advertisement and marketing exposures including print and broadcast media. Two studies measured the hours of TV and music video viewing. All measured drinking behaviour using a variety of outcome measures. Two studies evaluated drinkers and non-drinkers separately. Baseline non-drinkers were significantly more likely to have become a drinker at follow-up with greater exposure to alcohol advertisements. There was little difference in drinking frequency at follow-up in baseline drinkers. In studies that included drinkers and non-drinkers, increased exposure at baseline led to significant increased risk of drinking at follow-up. The strength of the relationship varied between studies but effect sizes were generally modest. All studies controlled for age and gender, however potential confounding factors adjusted for in analyses varied from study to study. Important risk factors such as peer drinking and parental attitudes and behaviour were not adequately accounted for in some studies. data from prospective cohort studies suggest there is an association between exposure to alcohol advertising or promotional activity and subsequent alcohol consumption in young people. Inferences about the modest effect sizes found are limited by the potential influence of residual or unmeasured confounding.

Effects of prenatal alcohol exposure on testosterone and pubertal development

PubMed Central

Carter, R.C.; Jacobson, J.L.; Dodge, N.C.; Granger, D.A.; Jacobson, S.W.

2014-01-01

Background Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic-pituitary-gonadal (HPG) axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development. Methods The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over-represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/mL), self-reported Tanner stages for pubertal development, and age at menarche (females). Results Prenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group X testosterone interaction term and potential confounders. Conclusions This study was the first to show a relation between prenatal alcohol exposure and increased testosterone during adolescence and evidence of decreased testosterone responsiveness in tissues related to pubertal development. Further studies examining androgen receptor expression and other hormonal and cellular factors affecting pubertal development may reveal important mechanisms underlying these teratogenic effects of alcohol exposure. PMID:24717169

Short term effects of air pollution on health: a European approach using epidemiologic time series data: the APHEA protocol.

PubMed Central

Katsouyanni, K; Schwartz, J; Spix, C; Touloumi, G; Zmirou, D; Zanobetti, A; Wojtyniak, B; Vonk, J M; Tobias, A; Pönkä, A; Medina, S; Bachárová, L; Anderson, H R

1996-01-01

BACKGROUND AND OBJECTIVES: Results from several studies over the past five years have shown that the current levels of pollutants in Europe and North America have adverse short term effects on health. The APHEA project aims to quantifying these in Europe, using standardised methodology. The project protocol and analytical methodology are presented here. DESIGN: Daily time series data were gathered for several air pollutants (sulphur dioxide; particulate matter, measured as total particles or as the particle fraction with an aerodynamic diameter smaller than a certain cut off, or as black smoke; nitrogen dioxide; and ozone) and health outcomes (the total and cause specific number of deaths and emergency hospital admissions). The data included fulfilled the quality criteria set by the APHEA protocol. SETTING: Fifteen European cities from 10 different countries with a total population over 25 million. METHODOLOGY: The APHEA collaborative group decided on a specific methodological procedure to control for confounding effects and evaluate the hypothesis. At the same time there was sufficient flexibility to allow local characteristics to be taken into account. The procedure included modelling of all potential confounding factors (that is, seasonal and long term patterns, meteorological factors, day of the week, holidays, and other unusual events), choosing the "best" air pollution models, and applying diagnostic tools to check the adequacy of the models. The final analysis used autoregressive Poisson models allowing for overdispersion. Effects were reported as relative risks contrasting defined increases in the corresponding pollutant levels. Each participating group applied the analyses to their own data. CONCLUSIONS: This methodology enabled results from many different European settings to be considered collectively. It represented the best available compromise between feasibility, comparability, and local adaptibility when using aggregated time series data not originally collected for the purpose of epidemiological studies. PMID:8758218

Defining sarcopenia in terms of risk of physical limitations: a 5-year follow-up study of 3,153 chinese men and women.

PubMed

Woo, Jean; Leung, Jason; Sham, Aprille; Kwok, Timothy

2009-12-01

To examine the definition of sarcopenia in Chinese subjects by relating the value of appendicular skeletal muscle mass (ASM) divided by height squared to physical functional outcomes after 4 years. Four-year prospective study. A Chinese community in Hong Kong SAR China. Three thousand one hundred fifty-three community-living men and women aged 65 and older. Information collected by questionnaire included demographics, health limitation on activities of daily living (ADLs), self-care, physical activity level, dietary intake, and psychosocial functioning. Measurements included height, weight, grip strength, step length in a 6-minute walk, and body composition. Four-year outcomes for those with ASM in kg per height in meters squared (ASM/ht(2)) less than 2 standard deviations (SDs) and 2 SDs or more below the young adult mean value were compared using analysis of variance and logistic regression, adjusting for potential confounding factors such as age, fat mass, presence or absence of malnutrition, dietary protein and vitamin D intake, comorbidity, and cognitive impairment. Participants with ASM/ht(2) 2 SDs or more below the young adult mean had lower grip strength and greater limitation in climbing stairs and general ADLs after adjusting for confounding factors. A U-shaped relationship was observed between physical limitation and ASM/ht(2), with increasing physical limitation below or above a range of 7.25 to 6.75 kg/m(2) in men and 6.00 to 6.25 kg/m(2) in women. Values of 5.25 to 6.74 kg/m(2) in women were associated with approximately 30% less risk of functional limitation after 5 years. No clear cutoff was found in men. Sarcopenia may be defined in terms of a range of values for ASM/ht(2) associated with the lowest risk of future physical limitations. The importance of establishing a quantitative value for the definition of sarcopenia may facilitate future interventional studies using pharmacological or nonpharmacological strategies.

Maternal age at first birth and offspring criminality: Using the children-of-twins design to test causal hypotheses

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behaviour. It is not clear if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children-of-siblings and children-of-twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant MZ twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association. PMID:23398750

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

PubMed

Wilkinson, Paul O; Croudace, Tim J; Goodyer, Ian M

2013-10-08

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

Maternal age at first birth and offspring criminality: using the children of twins design to test causal hypotheses.

PubMed

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D'Onofrio, Brian M

2013-02-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

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

PubMed

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

2014-08-27

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

Malignant Tumors of the Female Reproductive System

PubMed Central

Labrèche, France

2012-01-01

This review summarizes the epidemiology of cancer of the female reproductive system and associated lifestyle factors. It also assesses the available evidence for occupational factors associated with these cancers. Cervical, endometrial, and ovarian cancers are relatively common, and cause significant cancer morbidity and mortality worldwide, whereas vulvar, vaginal, fallopian tube cancers, and choriocarcinomas are very rare. As several lifestyle factors are known to play a major role in the etiology of these cancers, very few published studies have investigated possible relationships with occupational factors. Some occupational exposures have been associated with increased risks of these cancers, but apart from the available evidence on the relationships between asbestos fibers and ovarian cancer, and tetrachloroethylene and cervical cancer, the data is rather scarce. Given the multifactorial nature of cancers of the female reproductive system, it is of the utmost importance to conduct occupational studies that will gather detailed data on potential individual confounding factors, in particular reproductive history and other factors that influence the body's hormonal environment, together with information on socio-economic status and lifestyle factors, including physical activity from multiple sources. Studies on the mechanisms of carcinogenesis in the female reproductive organs are also needed in order to elucidate the possible role of chemical exposures in the development of these cancers. PMID:23019529

Prevention of motor‐vehicle deaths by changing vehicle factors

PubMed Central

Robertson, Leon S

2007-01-01

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

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

PubMed

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

2015-03-15

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

Flooding and mental health: a systematic mapping review.

PubMed

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

2015-01-01

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

Flooding and Mental Health: A Systematic Mapping Review

PubMed Central

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

2015-01-01

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