Infrared spectroscopic imaging detects chemical modifications in liver fibrosis due to diabetes and disease

PubMed Central

Sreedhar, Hari; Varma, Vishal K.; Gambacorta, Francesca V.; Guzman, Grace; Walsh, Michael J.

2016-01-01

The importance of stroma as a rich diagnostic region in tissue biopsies is growing as there is an increasing understanding that disease processes in multiple organs can affect the composition of adjacent connective tissue regions. This may be especially true in the liver, since this organ’s central metabolic role exposes it to multiple disease processes. We use quantum cascade laser infrared spectroscopic imaging to study changes in the chemical status of hepatocytes and fibrotic regions of liver tissue that result from the progression of liver cirrhosis to hepatocellular carcinoma and the potentially confounding effects of diabetes mellitus. PMID:27375956

Treatment with insulin analogs and prevalence of cardiovascular complications in patients with type 1 diabetes.

PubMed

Hasslacher, Christoph; Lorenzo Bermejo, Justo

2017-11-01

A lower incidence of cardiovascular events has been reported in type 2 diabetes patients treated with insulin analogs (IAs). Corresponding data on people affected by type 1 diabetes are not available yet. We investigated demographic and clinical data from 509 type 1 diabetics, who were treated in an outpatient clinic from 2006 to 2012. Multiple logistic regression was used to investigate the relationship between the type of insulin treatment and the prevalence of cardiovascular (CV) complications, that is, presence of coronary heart, cerebrovascular and peripheral arterial diseases, adjusting for potential confounders. Results from multiple logistic regression revealed that patients with impaired renal function [estimated glomerular filtration rate (eGFR) < 90 ml/min] show lower CV complication rates when treated with IAs (25%) compared with patients treated with human insulin (HI; 28%) and HI/IA (38%, p = 0.06). CV complication rates in the complete patient collective amounted to 17% (IA), 21% (HI) and 21% (HI/IA, p = 0.08). Examination of CV complications according to the type of IA revealed the lowest complication rates in type 1 diabetics treated with insulin lispro (5.9%) and glargine (16%). However, complication rate differences among insulin treatments did not reach statistical significance. The present cross-sectional study shows a borderline significantly lower CV morbidity in people with type 1 diabetes and impaired renal function when treated with IA compared with HI treatment after adjustment for multiple potential confounders [odds ratio (OR) = 0.78, which translates into a 22% lower complication rate]. Validation of these preliminary findings in confirmatory, prospective studies may have important clinical implications.

Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

PubMed

Castro, V M; Kong, S W; Clements, C C; Brady, R; Kaimal, A J; Doyle, A E; Robinson, E B; Churchill, S E; Kohane, I S; Perlis, R H

2016-01-05

Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.

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.

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

PubMed

Elvik, Rune

2011-11-01

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

Physical Activity and Bone Health in Schoolchildren: The Mediating Role of Fitness and Body Fat

PubMed Central

Torres-Costoso, Ana; Gracia-Marco, Luis; Sánchez-López, Mairena; Notario-Pacheco, Blanca; Arias-Palencia, Natalia; Martínez-Vizcaíno, Vicente

2015-01-01

Background The relationship between physical activity (PA) and bone health is well known, although the role of percent body fat (%BF) and fitness as confounders or mediators in this relationship remains uncertain. Objective To examine whether the association between PA and bone mineral content (BMC) is mediated by %BF and cardiorespiratory fitness (CRF). Methods In this cross sectional study, BMC, total %BF (by DXA), vigorous PA (VPA), CRF, age and height were measured in 132 schoolchildren (62 boys, aged 8–11 years). ANCOVA was used to test differences in BMC by %BF, CRF and VPA, controlling for different sets of confounders. Simple mediation analyses and serial multiple mediation analyses were fitted to examine whether the relationship between PA and BMC is mediated by %BF and fitness. Results Children with high %BF had higher total body BMC than their peers after controlling for all sets of confounders. Children with good CRF or VPA had significantly less total body BMC after controlling for age and sex but in children with good CRF this inverse relation disappeared after adjusting by %BF. %BF and CRF both act as a full mediator in the association between VPA and BMC, after inclusion of the potential confounders in the models. Conclusion Fitness and %BF seem to have a mediator role on the relationship between physical activity and bone mass. PMID:25915941

Assessing Omitted Confounder Bias in Multilevel Mediation Models.

PubMed

Tofighi, Davood; Kelley, Ken

2016-01-01

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

Perceived school safety is strongly associated with adolescent mental health problems.

PubMed

Nijs, Miesje M; Bun, Clothilde J E; Tempelaar, Wanda M; de Wit, Niek J; Burger, Huibert; Plevier, Carolien M; Boks, Marco P M

2014-02-01

School environment is an important determinant of psychosocial function and may also be related to mental health. We therefore investigated whether perceived school safety, a simple measure of this environment, is related to mental health problems. In a population-based sample of 11,130 secondary school students, we analysed the relationship of perceived school safety with mental health problems using multiple logistic regression analyses to adjust for potential confounders. Mental health problems were defined using the clinical cut-off of the self-reported Strengths and Difficulties Questionnaire. School safety showed an exposure-response relationship with mental health problems after adjustment for confounders. Odds ratios increased from 2.48 ("sometimes unsafe") to 8.05 ("very often unsafe"). The association was strongest in girls and young and middle-aged adolescents. Irrespective of the causal background of this association, school safety deserves attention either as a risk factor or as an indicator of mental health problems.

Startle reduces recall of a recently learned internal model.

PubMed

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

2011-01-01

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

Mediation Analysis: A Practitioner's Guide.

PubMed

VanderWeele, Tyler J

2016-01-01

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

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.

Cognitively-Impaired-Not-Demented Status Moderates the Time-Varying Association between Finger Tapping Inconsistency and Executive Performance.

PubMed

Halliday, Drew W R; Stawski, Robert S; MacDonald, Stuart W S

2017-02-01

Response time inconsistency (RTI) in cognitive performance predicts deleterious health outcomes in late-life; however, RTI estimates are often confounded by additional influences (e.g., individual differences in learning). Finger tapping is a basic sensorimotor measure largely independent of higher-order cognition that may circumvent such confounds of RTI estimates. We examined the within-person coupling of finger-tapping mean and RTI on working memory, and the moderation of these associations by cognitive status. A total of 262 older adults were recruited and classified as controls, cognitively-impaired-not-demented (CIND) unstable or CIND stable. Participants completed finger-tapping and working-memory tasks during multiple weekly assessments, repeated annually for 4 years. Within-person coupling estimates from multilevel models indicated that on occasions when RTI was greater, working-memory response latency was slower for the CIND-stable, but not for the CIND-unstable or control individuals. The finger-tapping task shows potential for minimizing confounds on RTI estimates, and for yielding RTI estimates sensitive to central nervous system function and cognitive status. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Rainfall and temperatures changes have confounding impacts on Phytophthora cinnamomi occurrence risk in the southwestern USA under climate change scenarios.

PubMed

Thompson, Sally E; Levin, Simon; Rodriguez-Iturbe, Ignacio

2014-04-01

Global change will simultaneously impact many aspects of climate, with the potential to exacerbate the risks posed by plant pathogens to agriculture and the natural environment; yet, most studies that explore climate impacts on plant pathogen ranges consider individual climatic factors separately. In this study, we adopt a stochastic modeling approach to address multiple pathways by which climate can constrain the range of the generalist plant pathogen Phytophthora cinnamomi (Pc): through changing winter soil temperatures affecting pathogen survival; spring soil temperatures and thus pathogen metabolic rates; and changing spring soil moisture conditions and thus pathogen growth rates through host root systems. We apply this model to the southwestern USA for contemporary and plausible future climate scenarios and evaluate the changes in the potential range of Pc. The results indicate that the plausible range of this pathogen in the southwestern USA extends over approximately 200,000 km(2) under contemporary conditions. While warming temperatures as projected by the IPCC A2 and B1 emissions scenarios greatly expand the range over which the pathogen can survive winter, projected reductions in spring rainfall reduce its feasible habitat, leading to spatially complex patterns of changing risk. The study demonstrates that temperature and rainfall changes associated with possible climate futures in the southwestern USA have confounding impacts on the range of Pc, suggesting that projections of future pathogen dynamics and ranges should account for multiple pathways of climate-pathogen interaction. © 2014 John Wiley & Sons Ltd.

Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma.

PubMed

Kumar, Shaji K; Laubach, Jacob P; Giove, Thomas J; Quick, Maureen; Neuwirth, Rachel; Yung, Godwin; Rajkumar, S Vincent; Richardson, Paul G

2017-09-01

Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1-4, 8-11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient-level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe BiPN compared with alternative dexamethasone dosing schedules. © 2017 John Wiley & Sons Ltd.

Waist Circumference and Objectively Measured Sedentary Behavior in Rural School Adolescents.

PubMed

Machado-Rodrigues, Aristides M; Coelho E Silva, Manuel J; Ribeiro, Luís P; Fernandes, Romulo; Mota, Jorge; Malina, Robert M

2016-01-01

Research on relationships between lifestyle behaviors and adiposity in school youth is potentially important for identifying subgroups at risk. This study evaluates the associations between waist circumference (WC) and objective measures of sedentary behavior (SB) in a sample of rural school adolescents. The sample included 254 students (114 boys, 140 girls), 13-16 years of age, from rural regions of the Portuguese midlands. Height, weight, and WC were measured. Cardiorespiratory fitness (CRF) was assessed with the 20-m shuttle-run test. An uniaxial GT1M accelerometer was used to obtain 5 consecutive days of physically activity (PA) and SB. Multiple linear regression was used to test associations between WC and SB, adjusted for several potential confounders (age, sex, PA, CRF, parental education). SB was not significantly associated with the WC, neither in the unadjusted model nor after adjustment for all potential confounders. In the final model, the unique significant predictor of the WC was cardiorespiratory fitness (β = -0.82; 95% confidence interval [CI], -1.02 to -0.62). WC was not independently associated with SB time in rural school adolescents. Future research is claimed among rural adolescents in different geographic contexts to try to clarify recent findings of less studied communities. © 2015, American School Health Association.

Avoiding false discoveries in association studies.

PubMed

Sabatti, Chiara

2007-01-01

We consider the problem of controlling false discoveries in association studies. We assume that the design of the study is adequate so that the "false discoveries" are potentially only because of random chance, not to confounding or other flaws. Under this premise, we review the statistical framework for hypothesis testing and correction for multiple comparisons. We consider in detail the currently accepted strategies in linkage analysis. We then examine the underlying similarities and differences between linkage and association studies and document some of the most recent methodological developments for association mapping.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-09-01

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

Pain of methadone-maintained heroin addicts: lonelier individuals feel more intense pain.

PubMed

Li, Fu; Xu, Yan-Min; Zhu, Jun-Hong; Lu, Jin; Zhong, Bao-Liang

2017-10-03

Managing pain in patients with heroin addiction is challenging, because most pain medications are addictive. A promising way to relieve pain of heroin addicts is to identify and address modifiable psychosocial factors associated with pain. This study examined the association between loneliness and pain intensity in Chinese heroin addicts receiving methadone maintenance treatment (MMT). A consecutive sample of 603 heroin addicts were recruited from three MMT clinics in Wuhan, China. Loneliness was assessed with a single question, and socio-demographic and clinical data were collected with a standardized questionnaire. Pain intensity was assessed with the five-point Verbal Rating Scale. Multiple ordinary logistic regression was used to control for potential confounders that may bias the loneliness-pain relationship. There was a significant and positive correlation between pain intensity and loneliness scores among methadone-maintained heroin addicts ( r = 0.453, P < 0.001). After controlling for potential socio-demographic and clinical confounders, an increase in the level of loneliness was significantly associated with an increase in pain intensity (OR = 1.22, P = 0.042). Loneliness is significantly associated with pain of methadone-maintained heroin addicts. Psychosocial interventions aimed at reducing loneliness might prevent or reduce pain of patients receiving MMT.

Polyunsaturated fatty acids in serum and homocysteine concentrations in Japanese men and women: a cross-sectional study.

PubMed

Kume, Ayami; Kurotani, Kayo; Sato, Masao; Ejima, Yuko; Pham, Ngoc Minh; Nanri, Akiko; Kuwahara, Keisuke; Mizoue, Tetsuya

2013-06-10

Supplementation studies have suggested a role of n-3 polyunsaturated fatty acids (PUFAs) in homocysteine metabolism, but the evidence is limited and inconsistent among studies that measured blood levels of n-3 and n-6 PUFAs. We examined the association between blood levels of PUFAs and homocysteine in Japanese men and women. The subjects were 496 employees (290 men and 206 women) of 2 municipal offices in Japan. Fatty acid composition in serum phospholipids and cholesterol ester (CE) was measured using gas-liquid chromatography. Multiple regression was used to calculate means of homocysteine concentrations according to PUFA tertile with adjustment for potential confounders. Serum homocysteine concentration decreased with increasing levels of total n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid (DHA) in serum phospholipids and CE with adjustment for age, sex and workplace. However, only DHA in serum phospholipids remained statistically significant after additional adjustment for other potential confounders including serum folate (P-trend = 0.04). N-6 PUFAs were not significantly associated with homocysteine concentrations. Higher proportion of DHA in serum phospholipids may be associated with lower homocysteine concentrations in Japanese men and women.

Does environmental confounding mask pleiotropic effects of a multiple sclerosis susceptibility variant on vitamin D in psychosis?

PubMed

Iyegbe, Conrad O; Acharya, Anita; Lally, John; Gardner-Sood, Poonam; Smith, Louise S; Smith, Shubulade; Murray, Robin; Howes, Oliver; Gaughran, Fiona

2015-01-01

This work addresses the existing and emerging evidence of overlap within the environmental and genetic profiles of multiple sclerosis (MS) and schizophrenia. To investigate whether a genetic risk factor for MS (rs703842), whose variation is indicative of vitamin D status in the disorder, could also be a determinant of vitamin D status in chronic psychosis patients. A cohort of 224 chronic psychosis cases was phenotyped and biologically profiled. The relationship between rs703842 and physiological vitamin D status in the blood plasma was assessed by logistic regression. Deficiency was defined as a blood plasma concentration below 10 ng/µl. Potential environmental confounders of the vitamin D status were considered as part of the analysis. We report suggestive evidence of an association with vitamin D status in established psychosis (ß standardized=0.51, P=0.04). The logistic model fit significantly benefited from controlling for body mass index, depression and ethnicity (χ (2)=91.7; 2 degrees of freedom (df); P=1.2×10(20)). The results suggest that, in addition to lifestyle changes that accompany the onset of illness, vitamin D dysregulation in psychosis has a genetic component that links into MS. Further, comprehensive studies are needed to evaluate this prospect.

Re-examining the link between prenatal maternal anxiety and child emotional difficulties, using a sibling design.

PubMed

Bekkhus, Mona; Lee, Yunsung; Nordhagen, Rannveig; Magnus, Per; Samuelsen, Sven O; Borge, Anne I H

2018-02-01

Prenatal exposure to maternal anxiety has been associated with child emotional difficulties in a number of epidemiological studies. One key concern, however, is that this link is vulnerable to confounding by pleiotropic genes or environmental family factors. Data on 82 383 mothers and children from the population-based Mother and Child Cohort Study and data on 21 980 siblings were used in this study. Mothers filled out questionnaires for each unique pregnancy, for infant difficulties at 6 months and for emotional difficulties at 36 months. The link between prenatal maternal anxiety and child difficulties were examined using logistic regression analyses and multiple linear regression analyses for the full study sample and the sibling sample. In the conventional full-cohort analyses, prenatal exposure to maternal anxiety was associated with child difficulties at both 6 months [odds ratio (OR) = 2.1 (1.94-2.27)] and 36 months [OR = 2.72 (2.47-2.99)]. The findings were essentially the same whether we examined difficulties at 6 months or at 36 months. However, these associations were no longer present once we controlled for potential social and genetic confounders in the sibling comparison analyses, either at 6 months [OR = 1.32 (0.91-1.90)] or at 36 months [OR = 1.28 (0.63-2.60)]. Findings from multiple regression analyses with continuous measures were essentially the same. Our finding lends little support for there being an independent prenatal effect on child emotional difficulties; rather, our findings suggest that the link between prenatal maternal anxiety and child difficulties could be confounded by pleiotropic genes or environmental family factors. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Stability and change of body mass index as a predictor of disability pension.

PubMed

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

2016-06-01

To investigate whether stability or change in body mass index (BMI) predict disability pension (DP) due to musculoskeletal diagnosis (MSD) when controlling for familial confounding. Our study cohort consisted of 17,169 Finnish twins born before 1958. Data on BMI and multiple covariates from questionnaires in 1975 and 1981 were included and DPs were collected from the national pension registers until the end of 2004. Cox proportional hazards regression models with Hazard Ratios (HR) and 95% Confidence Intervals (CI) were used for statistical analyses. General DP was granted to 2853 individuals and DP due to MSD to 1143 individuals during the 23-year follow-up. A one-unit increase in BMI in both 1975 (HR 1.08, 95% CI 1.05, 1.10) and 1981 (HR 1.06, 95% CI 1.04, 1.07), as well as the stability of and change in BMI from 1975 to 1981 were all associated with an increased risk of DP. These associations held in the analyses controlling for multiple covariates (age, sex, socioeconomic status, education, marital status, leisure-time physical activity, and musculoskeletal pain), and mainly also familial confounding, that is, genetics and shared environment. HR for stable obesity was 2.28 (95% CI 1.69, 3.08) for DP due to MSD, and 1.91 (95% CI 1.56, 2.34) for general DP in the fully adjusted models. CONCLUSIONS BMI IS AN EARLY PREDICTOR OF GENERAL DP AND ALSO OF DP DUE TO MSD OWING TO THE INDEPENDENCY OF VARIOUS COVARIATES AND POTENTIALLY ALSO FAMILIAL CONFOUNDING, BMI MAY POSSIBLY HAVE A DIRECT EFFECT ON THE RISK OF DP. © 2016 the Nordic Societies of Public Health.

Combining evidence from multiple electronic health care databases: performances of one-stage and two-stage meta-analysis in matched case-control studies.

PubMed

La Gamba, Fabiola; Corrao, Giovanni; Romio, Silvana; Sturkenboom, Miriam; Trifirò, Gianluca; Schink, Tania; de Ridder, Maria

2017-10-01

Clustering of patients in databases is usually ignored in one-stage meta-analysis of multi-database studies using matched case-control data. The aim of this study was to compare bias and efficiency of such a one-stage meta-analysis with a two-stage meta-analysis. First, we compared the approaches by generating matched case-control data under 5 simulated scenarios, built by varying: (1) the exposure-outcome association; (2) its variability among databases; (3) the confounding strength of one covariate on this association; (4) its variability; and (5) the (heterogeneous) confounding strength of two covariates. Second, we made the same comparison using empirical data from the ARITMO project, a multiple database study investigating the risk of ventricular arrhythmia following the use of medications with arrhythmogenic potential. In our study, we specifically investigated the effect of current use of promethazine. Bias increased for one-stage meta-analysis with increasing (1) between-database variance of exposure effect and (2) heterogeneous confounding generated by two covariates. The efficiency of one-stage meta-analysis was slightly lower than that of two-stage meta-analysis for the majority of investigated scenarios. Based on ARITMO data, there were no evident differences between one-stage (OR = 1.50, CI = [1.08; 2.08]) and two-stage (OR = 1.55, CI = [1.12; 2.16]) approaches. When the effect of interest is heterogeneous, a one-stage meta-analysis ignoring clustering gives biased estimates. Two-stage meta-analysis generates estimates at least as accurate and precise as one-stage meta-analysis. However, in a study using small databases and rare exposures and/or outcomes, a correct one-stage meta-analysis becomes essential. Copyright © 2017 John Wiley & Sons, Ltd.

Alternating treatments design: one strategy for comparing the effects of two treatments in a single subject.

PubMed Central

Barlow, D H; Hayes, S C

1979-01-01

A little used and often confused design, capable of comparing two treatments within a single subject, has been termed, variously, a multielement baseline design, a multiple schedule design, and a randomization design. The background of these terms is reviewed, and a new, more descriptive term, Alternating Treatments Design, is proposed. Critical differences between this design and a Simultaneous Treatment Design are outlined, and experimental questions answerable by each design are noted. Potential problems with multiple treatment interference in this procedure are divided into sequential confounding, carryover effects, and alternation effects and the importance of these issues vis-a-vis other single-case experimental designs is considered. Methods of minimizing multiple treatment interference as well as methods of studying these effects are outlined. Finally, appropriate uses of Alternating Treatments Designs are described and discussed in the context of recent examples. PMID:489478

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

PubMed

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

2017-11-01

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

Elevated C-reactive protein and posttraumatic stress pathology among survivors of the 9/11 World Trade Center attacks.

PubMed

Rosen, Rebecca L; Levy-Carrick, Nomi; Reibman, Joan; Xu, Ning; Shao, Yongzhao; Liu, Mengling; Ferri, Lucia; Kazeros, Angeliki; Caplan-Shaw, Caralee E; Pradhan, Deepak R; Marmor, Michael; Galatzer-Levy, Isaac R

2017-06-01

Systemic inflammation has emerged as a promising marker and potential mechanism underlying post-traumatic stress disorder (PTSD). The relationship between posttraumatic stress pathology and systemic inflammation has not, however, been consistently replicated and is potentially confounded by comorbid illness or injury, common complications of trauma exposure. We analyzed a large naturalistic cohort sharing a discrete physical and mental health trauma from the destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641). We evaluated the relationship between multiple physical and mental health related indices collected through routine evaluations at the WTC Environmental Health Center (WTC EHC), a treatment program for community members exposed to the disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance, negative cognitions/mood, arousal), depression and anxiety, while controlling for WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential risks or confounders. CRP was positively associated with PTSD severity (p < 0.001), trending toward association with depression (p = 0.06), but not with anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001) and avoidance (p < 0.05) symptom clusters, and trended toward associations with negative cognitions/mood (p = 0.06) and arousal (p = 0.08). In this large study of the relationship between CRP and posttraumatic stress pathology, we demonstrated an association between systemic inflammation and stress pathology (PTSD; trending with depression), which remained after adjusting for potentially confounding variables. These results contribute to research findings suggesting a salient relationship between inflammation and posttraumatic stress pathology. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2007-04-01

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

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

PubMed Central

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

2017-01-01

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

Confounder summary scores when comparing the effects of multiple drug exposures.

PubMed

Cadarette, Suzanne M; Gagne, Joshua J; Solomon, Daniel H; Katz, Jeffrey N; Stürmer, Til

2010-01-01

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2015-08-01

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

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 ...

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.

Leveraging Hierarchical Population Structure in Discrete Association Studies

PubMed Central

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

2007-01-01

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

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.

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

PubMed

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

2003-09-01

An increased rate of non-Hodgkin's lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult. 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. 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. Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention.

PubMed

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M; Stuart, Elizabeth A

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration.

An overview of confounding. Part 1: the concept and how to address it.

PubMed

Howards, Penelope P

2018-04-01

Confounding is an important source of bias, but it is often misunderstood. We consider how confounding occurs and how to address confounding using examples. Study results are confounded when the effect of the exposure on the outcome, mixes with the effects of other risk and protective factors for the outcome. This problem arises when these factors are present to different degrees among the exposed and unexposed study participants, but not all differences between the groups result in confounding. Thinking about an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe helps to distinguish confounders from other differences. In an actual study, an observed unexposed population is chosen to stand in for the unobserved parallel universe. Differences between this substitute population and the parallel universe result in confounding. Confounding by identified factors can be addressed analytically and through study design, but only randomization has the potential to address confounding by unmeasured factors. Nevertheless, a given randomized study may still be confounded. Confounded study results can lead to incorrect conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

How multiple causes combine: independence constraints on causal inference.

PubMed

Liljeholm, Mimi

2015-01-01

According to the causal power view, two core constraints-that causes occur independently (i.e., no confounding) and influence their effects independently-serve as boundary conditions for causal induction. This study investigated how violations of these constraints modulate uncertainty about the existence and strength of a causal relationship. Participants were presented with pairs of candidate causes that were either confounded or not, and that either interacted or exerted their influences independently. Consistent with the causal power view, uncertainty about the existence and strength of causal relationships was greater when causes were confounded or interacted than when unconfounded and acting independently. An elemental Bayesian causal model captured differences in uncertainty due to confounding but not those due to an interaction. Implications of distinct sources of uncertainty for the selection of contingency information and causal generalization are discussed.

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.

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.

Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

ERIC Educational Resources Information Center

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

2016-01-01

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

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

PubMed Central

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

2007-01-01

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

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-05-01

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

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

PubMed

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

2017-05-01

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

Associations between parity and maternal BMI in a population-based cohort study.

PubMed

Iversen, Ditte S; Kesmodel, Ulrik S; Ovesen, Per G

2018-06-01

We aimed to investigate the change in prevalence of overweight and obesity in pregnant Danish women from 2004 to 2012, and investigate whether increasing parity was associated with a change in body mass index (BMI) prevalence. We obtained a population-based cohort from the Danish Medical Birth Registry consisting of all Danish women giving birth in 2004-2012 (n = 572 321). This registry contains information on 99.8% of all births in Denmark. We calculated the overall change in prepregnancy BMI status among pregnant women in Denmark, and a multiple linear regression model with adjustment for several potential confounders was used to examine the change in prepregnancy BMI with increasing parity. In 2004, the prevalence of prepregnancy overweight and obesity (BMI ≥ 25) and obesity alone (BMI ≥ 30) was 31.9 and 11%, respectively. In 2012, the prevalence had reached 34.2 and 12.8%. The mean BMI increased for every additional parity from 23.80 (95% CI 23.77-23.82) in parity group 1 to 26.70 (26.52-26.90) in parity group 5+. A multiple linear regression adjusted for potential confounders showed that women on average gained 0.62 (0.58-0.65) BMI units after every additional birth. This study showed a 7.2% increase in overweight and obesity (BMI ≥ 25) and a 16.4% increase in obesity alone (BMI ≥ 30) for pregnant women in Denmark from 2004 to 2012. In addition, an increase in interpregnancy BMI was seen at every additional delivery, suggesting that obesity is an increasing challenge in obstetrics. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

A longitudinal comparative study of falls in persons with knee arthroplasty and persons with or at high risk for knee osteoarthritis.

PubMed

L Riddle, Daniel; J Golladay, Gregory

2016-11-01

we determined the yearly prevalence of single and multiple falls in persons with or at risk of knee osteoarthritis (OA) and persons undergoing knee arthroplasty over an 8-year period. We also compared annual fall rates among persons with and without knee arthroplasty to determine if fall rates are associated with knee arthroplasty. we studied 4,200 persons from the Osteoarthritis Imitative (OAI), a National Institutes of Health funded prospective study of persons 45-79 years and conducted from 2004 to 2012. All either had knee OA or were at risk of developing knee OA but did not have knee arthroplasty. The surgical group comprised 413 persons who underwent knee arthroplasty. Key fall risk factors were assessed at yearly study visits. Graphical depictions illustrated single and multiple fall trajectories. Multinomial regression adjusted for potential confounders compared fall rates for those with and without knee arthroplasty. fall rate trajectories for the two samples were generally flat and fall rates were similar. For the arthroplasty sample, fall rates did not increase in the immediate perioperative period relative to earlier and later periods. No differences in fall rates were found among the arthroplasty and non-arthroplasty samples after adjustment for potential confounding (P > 0.05). fall rates were generally stable and similar over an 8-year period among persons with and without knee arthroplasty. Clinicians should not assume that persons undergoing knee arthroplasty are at greater risk for falls either before or after surgery as compared to persons with or at risk for knee OA. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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

PubMed

Foo, Jong Yong Abdiel

2007-08-01

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

Network Analysis of Rodent Transcriptomes in Spaceflight

NASA Technical Reports Server (NTRS)

Ramachandran, Maya; Fogle, Homer; Costes, Sylvain

2017-01-01

Network analysis methods leverage prior knowledge of cellular systems and the statistical and conceptual relationships between analyte measurements to determine gene connectivity. Correlation and conditional metrics are used to infer a network topology and provide a systems-level context for cellular responses. Integration across multiple experimental conditions and omics domains can reveal the regulatory mechanisms that underlie gene expression. GeneLab has assembled rich multi-omic (transcriptomics, proteomics, epigenomics, and epitranscriptomics) datasets for multiple murine tissues from the Rodent Research 1 (RR-1) experiment. RR-1 assesses the impact of 37 days of spaceflight on gene expression across a variety of tissue types, such as adrenal glands, quadriceps, gastrocnemius, tibalius anterior, extensor digitorum longus, soleus, eye, and kidney. Network analysis is particularly useful for RR-1 -omics datasets because it reinforces subtle relationships that may be overlooked in isolated analyses and subdues confounding factors. Our objective is to use network analysis to determine potential target nodes for therapeutic intervention and identify similarities with existing disease models. Multiple network algorithms are used for a higher confidence consensus.

Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction-Having Your Cake and Eating It Two.

PubMed

Spiegelman, Donna; Rivera-Rodriguez, Claudia L; Haneuse, Sebastien

2016-07-01

In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis-in which detailed high-quality confounding data are obtained among a small subsample-can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake.

Shared processing in multiple object tracking and visual working memory in the absence of response order and task order confounds

PubMed Central

Howe, Piers D. L.

2017-01-01

To understand how the visual system represents multiple moving objects and how those representations contribute to tracking, it is essential that we understand how the processes of attention and working memory interact. In the work described here we present an investigation of that interaction via a series of tracking and working memory dual-task experiments. Previously, it has been argued that tracking is resistant to disruption by a concurrent working memory task and that any apparent disruption is in fact due to observers making a response to the working memory task, rather than due to competition for shared resources. Contrary to this, in our experiments we find that when task order and response order confounds are avoided, all participants show a similar decrease in both tracking and working memory performance. However, if task and response order confounds are not adequately controlled for we find substantial individual differences, which could explain the previous conflicting reports on this topic. Our results provide clear evidence that tracking and working memory tasks share processing resources. PMID:28410383

Shared processing in multiple object tracking and visual working memory in the absence of response order and task order confounds.

PubMed

Lapierre, Mark D; Cropper, Simon J; Howe, Piers D L

2017-01-01

To understand how the visual system represents multiple moving objects and how those representations contribute to tracking, it is essential that we understand how the processes of attention and working memory interact. In the work described here we present an investigation of that interaction via a series of tracking and working memory dual-task experiments. Previously, it has been argued that tracking is resistant to disruption by a concurrent working memory task and that any apparent disruption is in fact due to observers making a response to the working memory task, rather than due to competition for shared resources. Contrary to this, in our experiments we find that when task order and response order confounds are avoided, all participants show a similar decrease in both tracking and working memory performance. However, if task and response order confounds are not adequately controlled for we find substantial individual differences, which could explain the previous conflicting reports on this topic. Our results provide clear evidence that tracking and working memory tasks share processing resources.

Increasing atmospheric CO2 overrides the historical legacy of multiple stable biome states in Africa.

PubMed

Moncrieff, Glenn R; Scheiter, Simon; Bond, William J; Higgins, Steven I

2014-02-01

The dominant vegetation over much of the global land surface is not predetermined by contemporary climate, but also influenced by past environmental conditions. This confounds attempts to predict current and future biome distributions, because even a perfect model would project multiple possible biomes without knowledge of the historical vegetation state. Here we compare the distribution of tree- and grass-dominated biomes across Africa simulated using a dynamic global vegetation model (DGVM). We explicitly evaluate where and under what conditions multiple stable biome states are possible for current and projected future climates. Our simulation results show that multiple stable biomes states are possible for vast areas of tropical and subtropical Africa under current conditions. Widespread loss of the potential for multiple stable biomes states is projected in the 21st Century, driven by increasing atmospheric CO2 . Many sites where currently both tree-dominated and grass-dominated biomes are possible become deterministically tree-dominated. Regions with multiple stable biome states are widespread and require consideration when attempting to predict future vegetation changes. Testing for behaviour characteristic of systems with multiple stable equilibria, such as hysteresis and dependence on historical conditions, and the resulting uncertainty in simulated vegetation, will lead to improved projections of global change impacts. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Musculoskeletal pain and re-employment among unemployed job seekers: a three-year follow-up study.

PubMed

Nwaru, Chioma A; Nygård, Clas-Håkan; Virtanen, Pekka

2016-07-08

Poor health is a potential risk factor for not finding employment among unemployed individuals. We investigated the associations between localized and multiple-site musculoskeletal pain and re-employment in a three-year follow-up of unemployed job seekers. Unemployed people (n = 539) from six localities in southern Finland who participated in various active labour market policy measures at baseline in 2002/2003 were recruited into a three-year health service intervention trial. A questionnaire was used to collect data on musculoskeletal health and background characteristics at baseline and on employment status at the end of the follow-up. We conducted a complete case (n = 284) and multiple imputation analyses using logistic regression to investigate the association between baseline musculoskeletal pain and re-employment after three years. Participants with severe pain in the lower back were less likely to become re-employed. This was independent of potential confounding variables. Pain in the hands/upper extremities, neck/shoulders, lower extremities, as well as multiple site were not determinants of re-employment. Our findings lend some support to the hypothesis that poor health can potentially cause health selection into employment. There is the need to disentangle health problems in order to clearly appreciate their putative impact on employment. This will allow for more targeted interventions for the unemployed.

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

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.

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.

An overview of confounding. Part 2: how to identify it and special situations.

PubMed

Howards, Penelope P

2018-04-01

Confounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time-varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention

PubMed Central

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M.; Stuart, Elizabeth A.

2016-01-01

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration. PMID:27158217

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

PubMed

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

2017-12-29

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

Mapping Resting-State Brain Networks in Conscious Animals

PubMed Central

Zhang, Nanyin; Rane, Pallavi; Huang, Wei; Liang, Zhifeng; Kennedy, David; Frazier, Jean A.; King, Jean

2010-01-01

In the present study we mapped brain functional connectivity in the conscious rat at the “resting state” based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models. PMID:20382183

Effects of Multiple Maternal Relationship Transitions on Offspring Antisocial Behavior in Childhood and Adolescence: A Cousin-Comparison Analysis

PubMed Central

Goodnight, Jackson A.; D’Onofrio, Brian M.; Cherlin, Andrew J.; Emery, Robert E.; Van Hulle, Carol A.; Lahey, Benjamin B.

2012-01-01

Previous studies of the association between multiple parental relationship transitions (i.e., when a parent begins or terminates an intimate relationship involving cohabitation) and offspring antisocial behavior have varied in their efforts to rule out confounding influences, such as parental antisocial behavior and low income. They also have been limited in the representativeness of their samples. Thus, it remains unclear to what degree parents’ multiple relationship transitions have independent effects on children’s antisocial behavior. Analyses were conducted using data on 8,652 6–9-year-old, 6,911 10–13-year-old, and 6,495 14-17-year-old offspring of a nationally representative sample of U.S. women. Cousin-comparisons were used in combination with statistical covariates to evaluate the associations between maternal relationship transitions and offspring antisocial behavior in childhood and adolescence. Cousin-comparisons suggested that associations between maternal relationship transitions and antisocial behavior in childhood and early adolescence are largely explained by confounding factors. In contrast, the associations between maternal relationship transitions and offspring delinquency in late adolescence were robust to measured and unmeasured confounds. The present findings suggest that interventions aimed at reducing exposure to parental relationship transitions or addressing the psychosocial consequences of exposure to parental relationship transitions could reduce risk for offspring delinquency in late adolescence. PMID:22829173

Long-term exposure to particulate matter, NO2 and the oxidative potential of particulates and diabetes prevalence in a large national health survey.

PubMed

Strak, Maciej; Janssen, Nicole; Beelen, Rob; Schmitz, Oliver; Vaartjes, Ilonca; Karssenberg, Derek; van den Brink, Carolien; Bots, Michiel L; Dijst, Martin; Brunekreef, Bert; Hoek, Gerard

2017-11-01

The evidence from observational epidemiological studies of a link between long-term air pollution exposure and diabetes prevalence and incidence is currently mixed. Some studies found the strongest associations of diabetes with fine particles, other studies with nitrogen dioxide and some studies found no associations. Our aim was to investigate associations between long-term exposure to multiple air pollutants and diabetes prevalence in a large national survey in the Netherlands. We performed a cross-sectional analysis using the 2012 Dutch national health survey to investigate the associations between the 2009 annual average concentrations of multiple air pollutants (PM 10 , PM 2.5 , PM 10-2.5 , PM 2.5 absorbance, OP DTT , OP ESR and NO 2 ) and diabetes prevalence, among 289,703 adults. Air pollution exposure was assessed by land use regression models. Diabetes was defined based on a combined measure of self-reported physician diagnosis and medication prescription from an external database. Using logistic regression, we adjusted for potential confounders, including neighborhood- and individual socio-economic status and lifestyle-related risk factors such as smoking habits, alcohol consumption, physical activity and BMI. After adjustment for potential confounders, all pollutants (except PM 2.5 ) were associated with diabetes prevalence. In two-pollutant models, NO 2 and OP DTT remained associated with increased diabetes prevalence. For NO 2 and OP DTT , single-pollutant ORs per interquartile range were 1.07 (95% CI: 1.05, 1.09) and 1.08 (95% CI: 1.05, 1.10), respectively. Stratified analysis showed no consistent effect modification by any of the included known diabetes risk factors. Long-term residential air pollution exposure was associated with diabetes prevalence in a large health survey in the Netherlands, strengthening the evidence of air pollution being an important diabetes risk factor. Most consistent associations were observed for NO 2 and oxidative potential of PM 2.5 measured by the DTT assay. The finding of an association with the oxidative potential of fine particles but not with PM 2.5 , suggests that particle composition may be important for a potential effect on diabetes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2018-06-01

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

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

PubMed

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

2017-04-14

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

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

PubMed Central

Casey, Martin F.; Neidell, Matthew

2013-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Magnetic resonance imaging traits in siblings discordant for Alzheimer disease.

PubMed

Cuenco, Karen T; Green, Robert C; Zhang, J; Lunetta, Kathryn; Erlich, Porat M; Cupples, L Adrienne; Farrer, Lindsay A; DeCarli, Charles

2008-07-01

Magnetic resonance imaging (MRI) can aid clinical assessment of brain changes potentially correlated with Alzheimer disease (AD). MRI traits may improve our ability to identify genes associated with AD-outcomes. We evaluated semi-quantitative MRI measures as endophenotypes for genetic studies by assessing their association with AD in families from the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) Study. Discordant siblings from multiple ethnicities were ascertained through a single affected proband. Semi-quantitative MRI measures were obtained for each individual. The association between continuous/ordinal MRI traits and AD were analyzed using generalized estimating equations. Medical history and Apolipoprotein E (APOE)epsilon4 status were evaluated as potential confounders. Comparisons of 214 affected and 234 unaffected subjects from 229 sibships revealed that general cerebral atrophy, white matter hyperintensities (WMH), and mediotemporal atrophy differed significantly between groups (each at P < .0001) and varied by ethnicity. Age at MRI and duration of AD confounded all associations between AD and MRI traits. Among unaffected sibs, the presence of at least one APOEepsilon4 allele and MRI infarction was associated with more WMH after adjusting for age at MRI. The strong association between MRI traits and AD suggests that MRI traits may be informative endophenotypes for basic and clinical studies of AD. In particular, WMH may be a marker of vascular disease that contributes to AD pathogenesis.

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

Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids

PubMed Central

McKay, Gareth J; Loane, Edward; Nolan, John M; Patterson, Christopher C; Meyers, Kristin J; Mares, Julie A; Yonova-Doing, Ekaterina; Hammond, Christopher J; Beatty, Stephen; Silvestri, Giuliana

2013-01-01

Objective To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). Design A cross-sectional study of healthy adults aged 20-70. Participants 302 participants recruited following local advertisement. Methods MPOD was measured by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by HPLC and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and CAREDS cohorts. Main outcome measures Odds ratios (ORs) for macular pigment optical density area, serum lutein and zeaxanthin concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and sex. Results Following multiple regression analysis with adjustment for age, body mass index, sex, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, smoking, dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P=0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P=2×10−4), a SNP in high linkage disequilibrium with rs11057841 (r2=0.93). No significant interactions by sex were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. Conclusions Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of AMD risk through combating the effects of oxidative stress within the retina. PMID:23562302

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

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

PubMed

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

2018-01-01

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

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

PubMed

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

2012-10-01

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

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.

The Interrelation of Prayer and Worship Service Attendance in Moderating the Negative Impact of Life Event Stressors on Mental Well-Being.

PubMed

Rainville, G

2017-09-13

The interrelation of worship service attendance and private prayer in moderating the negative impact of life event stressors on mental well-being is examined using hierarchical multiple regressions on a national sample of 2601 Americans. A theoretical model is proposed in which stressful life events are made less distressing under conditions in which exposure to pro-social content at worship services is internalized through frequent private prayer. Interactive models controlling for a block of potential confounds are run to confirm that the stress-moderating effects of worship service attendance are noted only when attendance is complemented by relatively frequent engagement in private prayer.

Housing Instability and Children's Health Insurance Gaps.

PubMed

Carroll, Anne; Corman, Hope; Curtis, Marah A; Noonan, Kelly; Reichman, Nancy E

To assess the extent to which housing instability is associated with gaps in health insurance coverage of preschool-age children. Secondary analysis of data from the Early Childhood Longitudinal Study-Birth Cohort, a nationally representative study of children born in the United States in 2001, was conducted to investigate associations between unstable housing-homelessness, multiple moves, or living with others and not paying rent-and children's subsequent health insurance gaps. Logistic regression was used to adjust for potentially confounding factors. Ten percent of children were unstably housed at age 2, and 11% had a gap in health insurance between ages 2 and 4. Unstably housed children were more likely to have gaps in insurance compared to stably housed children (16% vs 10%). Controlling for potentially confounding factors, the odds of a child insurance gap were significantly higher in unstably housed families than in stably housed families (adjusted odds ratio 1.27; 95% confidence interval 1.01-1.61). The association was similar in alternative model specifications. In a US nationally representative birth cohort, children who were unstably housed at age 2 were at higher risk, compared to their stably housed counterparts, of experiencing health insurance gaps between ages 2 and 4 years. The findings from this study suggest that policy efforts to delink health insurance renewal processes from mailing addresses, and potentially routine screenings for housing instability as well as referrals to appropriate resources by pediatricians, would help unstably housed children maintain health insurance. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

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

PubMed

Karmon, Anatte; Sheiner, Eyal

2008-06-01

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

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

PubMed

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

2016-09-01

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

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

PubMed Central

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

2016-01-01

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

Preeclampsia and retinopathy of prematurity in preterm births.

PubMed

Yu, Xiao Dan; Branch, D Ware; Karumanchi, S Ananth; Zhang, Jun

2012-07-01

The relationship between gestational hypertension, preeclampsia, and the risk of retinopathy of prematurity (ROP) remains unclear. Thus, we used a large cohort database to study the influence of maternal gestational hypertension and preeclampsia on the occurrence of ROP in preterm infants. We used data from a previous retrospective cohort study that includes 25,473 eligible preterm neonates. We examined the association between gestational hypertension, preeclampsia, and ROP while controlling for potential confounders by multiple logistic regression analysis. Of the 8758 early preterm infants (gestational age <34 weeks), 1024 (11.69%) had ROP, while of the 16,715 late preterm infants, only 29 (0.17%) had ROP. After adjusting for confounders, preeclampsia was associated with a significantly reduced risk of ROP (adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI], 0.49-0.86 for early preterm birth; aOR, 0.10; 95% CI, 0.01-0.93 for late preterm birth; aOR, 0.66; 95% CI, 0.50-0.87 for all preterm births). Gestational hypertension was not significantly associated with ROP at early or late preterm births. Preeclampsia, but not gestational hypertension, was associated with a reduced risk of ROP in preterm births.

Smoking and cognitive impairment among older persons in Malaysia.

PubMed

Momtaz, Yadollah Abolfathi; Ibrahim, Rahimah; Hamid, Tengku Aizan; Chai, Sen Tyng

2015-06-01

Previous studies have shown conflicting results on the association between smoking and cognitive function. This study aims to examine the relationship of smoking with cognitive function. Data for the study, consisting of 2553 older adults aged 60 years and older, were drawn from a nationwide household survey entitled "Determinants of Wellness among Older Malaysians: A Health Promotion Perspective" conducted in 2010. Current smokers had lower rates of cognitive impairment compared to never smokers (17.4% vs 25.9%), while cognitive function in former or ex-smokers was almost similar to that of the never smokers. Findings from multiple logistic regression analysis showed that current smokers were 37% less likely to be cognitively impaired, compared to the never smokers (odds ratio [OR] = .63; 95% confidence interval [CI]: .46-.86) while controlling for potential confounders. No difference in cognitive function was observed between former smokers and never smokers (OR = .94; 95% CI: .71-1.25). Although the findings indicated a negative association between cigarette smoking and cognitive impairment, we are unable to conclude whether this relationship is causal or affected by other unmeasured confounding factors, especially survival bias. © The Author(s) 2014.

Frequency of soup intake and amount of dietary fiber intake are inversely associated with plasma leptin concentrations in Japanese adults.

PubMed

Kuroda, Motonaka; Ohta, Masanori; Okufuji, Tatsuya; Takigami, Chieko; Eguchi, Masafumi; Hayabuchi, Hitomi; Ikeda, Masaharu

2010-06-01

Previous studies have shown that the intake of soup negatively correlates with the body mass index (BMI), suggesting that soup intake reduces the risk of obesity. In this study, to clarify the association of the intake of soup and various nutrients with plasma leptin concentration, a cross-sectional study on 504 Japanese adults aged 20-76 years (103 men and 401 women) was performed. The intake of soup and various nutrients was investigated by food frequency questionnaires. Plasma leptin concentration was measured in fasting blood by radioimmunoassay. The correlation was analyzed by multiple regression analysis. The average frequency of soup intake was 7.6 times/week. The average plasma leptin concentration was 7.76 ng/ml. After adjusting the confounding factors, the frequency of soup intake has a significant inverse association with plasma leptin concentration. Among the macronutrients, only dietary fiber intake negatively correlated with plasma leptin concentration after the adjustment for potential confounding factors. These results suggest that the intakes of soup and dietary fiber were negatively correlated with plasma leptin concentration in Japanese adults. Copyright 2010 Elsevier Ltd. All rights reserved.

Estimating scaled treatment effects with multiple outcomes.

PubMed

Kennedy, Edward H; Kangovi, Shreya; Mitra, Nandita

2017-01-01

In classical study designs, the aim is often to learn about the effects of a treatment or intervention on a single outcome; in many modern studies, however, data on multiple outcomes are collected and it is of interest to explore effects on multiple outcomes simultaneously. Such designs can be particularly useful in patient-centered research, where different outcomes might be more or less important to different patients. In this paper, we propose scaled effect measures (via potential outcomes) that translate effects on multiple outcomes to a common scale, using mean-variance and median-interquartile range based standardizations. We present efficient, nonparametric, doubly robust methods for estimating these scaled effects (and weighted average summary measures), and for testing the null hypothesis that treatment affects all outcomes equally. We also discuss methods for exploring how treatment effects depend on covariates (i.e., effect modification). In addition to describing efficiency theory for our estimands and the asymptotic behavior of our estimators, we illustrate the methods in a simulation study and a data analysis. Importantly, and in contrast to much of the literature concerning effects on multiple outcomes, our methods are nonparametric and can be used not only in randomized trials to yield increased efficiency, but also in observational studies with high-dimensional covariates to reduce confounding bias.

Childhood maltreatment and adulthood poor sleep quality: a longitudinal study.

PubMed

Abajobir, Amanuel A; Kisely, Steve; Williams, Gail; Strathearn, Lane; Najman, Jake M

2017-08-01

Available evidence from cross-sectional studies suggests that childhood maltreatment may be associated with a range of sleep disorders. However, these studies have not controlled for potential individual-, familial- and environmental-level confounders. To determine the association between childhood maltreatment and lower sleep quality after adjusting for potential confounders. Data for the present study were obtained from a pre-birth cohort study of 3778 young adults (52.6% female) of the Mater Hospital-University of Queensland Study of Pregnancy follow up at a mean age of 20.6 years. The Mater Hospital-University of Queensland Study of Pregnancy is a prospective Australian pre-birth cohort study of mothers consecutively recruited during their first obstetric clinic visit at Brisbane's Mater Hospital in 1981-1983. Participants completed the Pittsburgh Sleep Quality Index at the 21-year follow up. We linked this dataset to agency-recorded substantiated cases of childhood maltreatment. A series of separate logistic regression models was used to test whether childhood maltreatment predicted lower sleep quality after adjustment for selected confounders. Substantiated physical abuse significantly predicted lower sleep quality in males. Single and multiple forms of childhood maltreatment, including age of maltreatment and number of substantiations, did not predict lower sleep quality in either gender in both crude and adjusted models. Not being married, living in a residential problem area, cigarette smoking and internalising were significantly associated with lower sleep quality in a fully adjusted model for the male-female combined sample. Childhood maltreatment does not appear to predict young adult poor sleep quality, with the exception of physical abuse for males. While childhood maltreatment has been found to predict a range of mental health problems, childhood maltreatment does not appear to predict sleep problems occurring in young adults. Poor sleep quality was accounted for by concurrent social disadvantage, cigarette smoking and internalising. © 2017 Royal Australasian College of Physicians.

Interventional effects for mediation analysis with multiple mediators

PubMed Central

Vansteelandt, Stijn; Daniel, Rhian M.

2016-01-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins21 introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal in order to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when – as often – the structural dependence between the multiple mediators is unknown; for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators. PMID:27922534

Interventional Effects for Mediation Analysis with Multiple Mediators.

PubMed

Vansteelandt, Stijn; Daniel, Rhian M

2017-03-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

The physical health of British adults with intellectual disability: cross sectional study.

PubMed

Emerson, Eric; Hatton, Chris; Baines, Susannah; Robertson, Janet

2016-01-20

Adults with intellectual disability have poorer health than their non-disabled peers. However, little is known about the health of the 'hidden majority' of adults with primarily mild intellectual disability who do not use intellectual disability services. The aims of the present study were: to estimate the physical health status of a population-based sample of British adults with and without mild intellectual disability while controlling for any potentially confounding effects resulting from between-group differences in gender, age, socio-economic disadvantage and neighborhood social capital. Secondary analysis of data from Understanding Society, a new longitudinal study focusing on the life experiences of UK citizens. We identified 299 participants aged 16-49 (1.2 % of the unweighted age-restricted sample) as having intellectual disability, and 22,927 as not having intellectual disability. Multivariate logistic regression was used to investigate between group differences adjusting for potential confounding personal characteristics (e.g., gender). Unadjusted comparisons indicated that British adults with intellectual disability have markedly poorer health than their non-disabled peers on the majority of indicators investigated including self-rated health, multiple morbidity, arthritis, cancer, diabetes, obesity, measured grip strength, measured lung function and polypharmacy. Adjusting for between-group differences in age and gender had a marginal impact on these estimates. Further adjusting for between-group differences in socio-economic disadvantage and neighborhood quality had a more marked impact on estimates with the number of statistically significant differences reducing from 13 to 8 and statistically significant attenuation of odds on three indicators (self-rated health, SF-12 physical component and multiple morbidity). The 'hidden majority' of adults with primarily mild intellectual disability who do not use intellectual disability services have significantly poorer health than their non-disabled peers. This may, in part, reflect their increased risk of exposure to well established 'social determinants' of poorer health.

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 ...

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

PubMed Central

Schellenberg, Joanna; Todd, Jim

2011-01-01

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

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

PubMed

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

2018-05-21

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

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.

Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study.

PubMed

Fenton, Tanis R; Eliasziw, Misha; Tough, Suzanne C; Lyon, Andrew W; Brown, Jacques P; Hanley, David A

2010-05-10

The acid-ash hypothesis, the alkaline diet, and related products are marketed to the general public. Websites, lay literature, and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis.The objectives of this study were to determine whether 1) low urine pH, or 2) acid excretion in urine [sulfate + chloride + 1.8x phosphate + organic acids] minus [sodium + potassium + 2x calcium + 2x magnesium mEq] in fasting morning urine predict: a) fragility fractures; and b) five-year change of bone mineral density (BMD) in adults. Cohort study: the prospective population-based Canadian Multicentre Osteoporosis Study. Multiple logistic regression was used to examine associations between acid excretion (urine pH and urine acid excretion) in fasting morning with the incidence of fractures (6804 person years). Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites: lumbar spine, femoral neck, and total hip (n = 651). Potential confounders controlled included: age, gender, family history of osteoporosis, physical activity, smoking, calcium intake, vitamin D status, estrogen status, medications, renal function, urine creatinine, body mass index, and change of body mass index. There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders. Urine pH and urine acid excretion do not predict osteoporosis risk.

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.

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.

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

PubMed Central

Smith, Eric G.

2015-01-01

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

Glyphosate epidemiology expert panel review: a weight of evidence systematic review of the relationship between glyphosate exposure and non-Hodgkin's lymphoma or multiple myeloma.

PubMed

Acquavella, John; Garabrant, David; Marsh, Gary; Sorahan, Tom; Weed, Douglas L

2016-09-01

We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) - two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses. Our evaluation included seven unique studies for NHL and four for MM, all but one of which were case control studies for each cancer. For NHL, the case-control studies were all limited by the potential for recall bias and the lack of adequate multivariate adjustment for multiple pesticide and other farming exposures. Only the Agricultural Health (cohort) Study met our a priori quality standards and this study found no evidence of an association between glyphosate and NHL. For MM, the case control studies shared the same limitations as noted for the NHL case-control studies and, in aggregate, the data were too sparse to enable an informed causal judgment. Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM.

Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China.

PubMed

Feng, Wei; Cui, Xiuqing; Liu, Bing; Liu, Chuanyao; Xiao, Yang; Lu, Wei; Guo, Huan; He, Meian; Zhang, Xiaomin; Yuan, Jing; Chen, Weihong; Wu, Tangchun

2015-01-01

Elevated heavy metals and fasting plasma glucose (FPG) levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population. We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR) method to correct for multiple hypothesis tests. After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05). After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05). Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings.

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

PubMed

Bollen, Kenneth A

2007-06-01

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

Fluorescent probes for the simultaneous detection of multiple analytes in biology.

PubMed

Kolanowski, Jacek L; Liu, Fei; New, Elizabeth J

2018-01-02

Many of the key questions facing cellular biology concern the location and concentration of chemical species, from signalling molecules to metabolites to exogenous toxins. Fluorescent sensors (probes) have revolutionised the understanding of biological systems through their exquisite sensitivity to specific analytes. Probe design has focussed on selective sensors for individual analytes, but many of the most pertinent biological questions are related to the interaction of more than one chemical species. While it is possible to simultaneously use multiple sensors for such applications, data interpretation will be confounded by the fact that sensors will have different uptake, localisation and metabolism profiles. An alternative solution is to instead use a single probe that responds to two analytes, termed a dual-responsive probe. Recent progress in this field has yielded exciting probes, some of which have demonstrated biological application. Here we review work that has been carried out to date, and suggest future research directions that will harness the considerable potential of dual-responsive fluorescent probes.

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…

Understanding the Cycle

PubMed Central

Currie, Janet; Tekin, Erdal

2013-01-01

Child maltreatment is a major social problem. This paper focuses on measuring the relationship between child maltreatment and crime using data from the National Longitudinal Study of Adolescent Health (Add Health). We focus on crime because it is one of the most costly potential outcomes of maltreatment. Our work addresses two main limitations of the existing literature on child maltreatment. First, we use a large national sample, and investigate different types of maltreatment in a unified framework. Second, we pay careful attention to controlling for possible confounders using a variety of statistical methods that make differing assumptions. The results suggest that maltreatment greatly increases the probability of engaging in crime and that the probability increases with the experience of multiple forms of maltreatment. PMID:24204082

Brief report: life history and neuropathology of a gifted man with Asperger syndrome.

PubMed

Weidenheim, Karen M; Escobar, Alfonso; Rapin, Isabelle

2012-03-01

Despite recent interest in the pathogenesis of the autism spectrum disorders (pervasive developmental disorders), neuropathological descriptions of brains of individuals with well documented clinical information and without potentially confounding symptomatology are exceptionally rare. Asperger syndrome differs from classic autism by lack of cognitive impairment or delay in expressive language acquisition. We examined the 1,570 g brain of a 63 year old otherwise healthy mathematician with an Autistic Spectrum Disorder of Asperger subtype. Except for an atypical gyral pattern and megalencephaly, we detected no specific neuropathologic abnormality. Taken together, the behavioral data and pathological findings in this case are compatible with an early neurodevelopmental process affecting multiple neuroanatomic networks, but without a convincing morphologic signature detectable with routine neuropathologic technology.

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.

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

ERIC Educational Resources Information Center

Games, Paul A.

1975-01-01

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

Presenting evidence and summary measures to best inform societal decisions when comparing multiple strategies.

PubMed

Eckermann, Simon; Willan, Andrew R

2011-07-01

Multiple strategy comparisons in health technology assessment (HTA) are becoming increasingly important, with multiple alternative therapeutic actions, combinations of therapies and diagnostic and genetic testing alternatives. Comparison under uncertainty of incremental cost, effects and cost effectiveness across more than two strategies is conceptually and practically very different from that for two strategies, where all evidence can be summarized in a single bivariate distribution on the incremental cost-effectiveness plane. Alternative methods for comparing multiple strategies in HTA have been developed in (i) presenting cost and effects on the cost-disutility plane and (ii) summarizing evidence with multiple strategy cost-effectiveness acceptability (CEA) and expected net loss (ENL) curves and frontiers. However, critical questions remain for the analyst and decision maker of how these techniques can be best employed across multiple strategies to (i) inform clinical and cost inference in presenting evidence, and (ii) summarize evidence of cost effectiveness to inform societal reimbursement decisions where preferences may be risk neutral or somewhat risk averse under the Arrow-Lind theorem. We critically consider how evidence across multiple strategies can be best presented and summarized to inform inference and societal reimbursement decisions, given currently available methods. In the process, we make a number of important original findings. First, in presenting evidence for multiple strategies, the joint distribution of costs and effects on the cost-disutility plane with associated flexible comparators varying across replicates for cost and effect axes ensure full cost and effect inference. Such inference is usually confounded on the cost-effectiveness plane with comparison relative to a fixed origin and axes. Second, in summarizing evidence for risk-neutral societal decision making, ENL curves and frontiers are shown to have advantages over the CEA frontier in directly presenting differences in expected net benefit (ENB). The CEA frontier, while identifying strategies that maximize ENB, only presents their probability of maximizing net benefit (NB) and, hence, fails to explain why strategies maximize ENB at any given threshold value. Third, in summarizing evidence for somewhat risk-averse societal decision making, trade-offs between the strategy maximizing ENB and other potentially optimal strategies with higher probability of maximizing NB should be presented over discrete threshold values where they arise. However, the probabilities informing these trade-offs and associated discrete threshold value regions should be derived from bilateral CEA curves to prevent confounding by other strategies inherent in multiple strategy CEA curves. Based on these findings, a series of recommendations are made for best presenting and summarizing cost-effectiveness evidence for reimbursement decisions when comparing multiple strategies, which are contrasted with advice for comparing two strategies. Implications for joint research and reimbursement decisions are also discussed.

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

PubMed

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

2016-02-01

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

Procedural Factors That Affect Psychophysical Measures of Spatial Selectivity in Cochlear Implant Users

PubMed Central

Deeks, John M.; Carlyon, Robert P.

2015-01-01

Behavioral measures of spatial selectivity in cochlear implants are important both for guiding the programing of individual users’ implants and for the evaluation of different stimulation methods. However, the methods used are subject to a number of confounding factors that can contaminate estimates of spatial selectivity. These factors include off-site listening, charge interactions between masker and probe pulses in interleaved masking paradigms, and confusion effects in forward masking. We review the effects of these confounds and discuss methods for minimizing them. We describe one such method in which the level of a 125-pps masker is adjusted so as to mask a 125-pps probe, and where the masker and probe pulses are temporally interleaved. Five experiments describe the method and evaluate the potential roles of the different potential confounding factors. No evidence was obtained for off-site listening of the type observed in acoustic hearing. The choice of the masking paradigm was shown to alter the measured spatial selectivity. For short gaps between masker and probe pulses, both facilitation and refractory mechanisms had an effect on masking; this finding should inform the choice of stimulation rate in interleaved masking experiments. No evidence for confusion effects in forward masking was revealed. It is concluded that the proposed method avoids many potential confounds but that the choice of method should depend on the research question under investigation. PMID:26420785

Prenatal Stress due to a Natural Disaster Predicts Adiposity in Childhood: The Iowa Flood Study

PubMed Central

Dancause, Kelsey N.; Laplante, David P.; Hart, Kimberly J.; O'Hara, Michael W.; Brunet, Alain

2015-01-01

Prenatal stress can affect lifelong physical growth, including increased obesity risk. However, human studies remain limited. Natural disasters provide models of independent stressors unrelated to confounding maternal characteristics. We assessed degree of objective hardship and subjective distress in women pregnant during severe flooding. At ages 2.5 and 4 years we assessed body mass index (BMI), subscapular plus triceps skinfolds (SS + TR, an index of total adiposity), and SS : TR ratio (an index of central adiposity) in their children (n = 106). Hierarchical regressions controlled first for several potential confounds. Controlling for these, flood exposure during early gestation predicted greater BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater maternal hardship and distress due to the floods, as well as other nonflood life events during pregnancy, independently predicted greater increase in total adiposity between 2.5 and 4 years. These results support the hypothesis that prenatal stress increases adiposity beginning in childhood and suggest that early gestation is a sensitive period. Results further highlight the additive effects of maternal objective and subjective stress, life events, and depression, emphasizing the importance of continued studies on multiple, detailed measures of maternal mental health and experience in pregnancy and child growth. PMID:25874124

Prenatal stress due to a natural disaster predicts adiposity in childhood: the Iowa Flood Study.

PubMed

Dancause, Kelsey N; Laplante, David P; Hart, Kimberly J; O'Hara, Michael W; Elgbeili, Guillaume; Brunet, Alain; King, Suzanne

2015-01-01

Prenatal stress can affect lifelong physical growth, including increased obesity risk. However, human studies remain limited. Natural disasters provide models of independent stressors unrelated to confounding maternal characteristics. We assessed degree of objective hardship and subjective distress in women pregnant during severe flooding. At ages 2.5 and 4 years we assessed body mass index (BMI), subscapular plus triceps skinfolds (SS + TR, an index of total adiposity), and SS : TR ratio (an index of central adiposity) in their children (n = 106). Hierarchical regressions controlled first for several potential confounds. Controlling for these, flood exposure during early gestation predicted greater BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater maternal hardship and distress due to the floods, as well as other nonflood life events during pregnancy, independently predicted greater increase in total adiposity between 2.5 and 4 years. These results support the hypothesis that prenatal stress increases adiposity beginning in childhood and suggest that early gestation is a sensitive period. Results further highlight the additive effects of maternal objective and subjective stress, life events, and depression, emphasizing the importance of continued studies on multiple, detailed measures of maternal mental health and experience in pregnancy and child growth.

Thyroid status and 6-year mortality in elderly people living in a mildly iodine-deficient area: the aging in the Chianti Area Study.

PubMed

Ceresini, Graziano; Ceda, Gian Paolo; Lauretani, Fulvio; Maggio, Marcello; Usberti, Elisa; Marina, Michela; Bandinelli, Stefania; Guralnik, Jack M; Valenti, Giorgio; Ferrucci, Luigi

2013-06-01

To test the hypothesis that, in older adults, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with mortality independent of potential confounders. Longitudinal. Community-based. Nine hundred fifty-one individuals aged 65 and older. Plasma thyrotropin, free thyroxine, and free triiodothyronine concentrations and demographic features were evaluated in participants of the Invecchiare in Chianti Study aged 65 and older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Eight hundred nineteen participants were euthyroid, 83 had subclinical hyperthyroidism (SHyper), and 29 had subclinical hypothyroidism (SHypo). Overt hypo- and hyperthyroidism were found in five and 15 subjects, respectively. During a median of 6 years of follow-up, 210 deaths occurred (22.1%), 98 (46.6%) of which were from cardiovascular causes. Kaplan-Meier analysis revealed higher overall mortality for SHyper (P = .04) than euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.02-2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality. In euthyroid subjects, thyrotropin was found to be predictive of lower risk of all-cause mortality (HR = 0.76, 95% CI = 0.57-0.99). SHyper is an independent risk factor for all-cause mortality in older adults. Low to normal circulating thyrotropin should be carefully monitored in elderly euthyroid individuals. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

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

PubMed Central

Varadhan, Ravi; Wang, Sue-Jane

2016-01-01

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

Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer

PubMed Central

2012-01-01

Background Automated classification of histopathology involves identification of multiple classes, including benign, cancerous, and confounder categories. The confounder tissue classes can often mimic and share attributes with both the diseased and normal tissue classes, and can be particularly difficult to identify, both manually and by automated classifiers. In the case of prostate cancer, they may be several confounding tissue types present in a biopsy sample, posing as major sources of diagnostic error for pathologists. Two common multi-class approaches are one-shot classification (OSC), where all classes are identified simultaneously, and one-versus-all (OVA), where a “target” class is distinguished from all “non-target” classes. OSC is typically unable to handle discrimination of classes of varying similarity (e.g. with images of prostate atrophy and high grade cancer), while OVA forces several heterogeneous classes into a single “non-target” class. In this work, we present a cascaded (CAS) approach to classifying prostate biopsy tissue samples, where images from different classes are grouped to maximize intra-group homogeneity while maximizing inter-group heterogeneity. Results We apply the CAS approach to categorize 2000 tissue samples taken from 214 patient studies into seven classes: epithelium, stroma, atrophy, prostatic intraepithelial neoplasia (PIN), and prostate cancer Gleason grades 3, 4, and 5. A series of increasingly granular binary classifiers are used to split the different tissue classes until the images have been categorized into a single unique class. Our automatically-extracted image feature set includes architectural features based on location of the nuclei within the tissue sample as well as texture features extracted on a per-pixel level. The CAS strategy yields a positive predictive value (PPV) of 0.86 in classifying the 2000 tissue images into one of 7 classes, compared with the OVA (0.77 PPV) and OSC approaches (0.76 PPV). Conclusions Use of the CAS strategy increases the PPV for a multi-category classification system over two common alternative strategies. In classification problems such as histopathology, where multiple class groups exist with varying degrees of heterogeneity, the CAS system can intelligently assign class labels to objects by performing multiple binary classifications according to domain knowledge. PMID:23110677

Propensity score models in observational comparative effectiveness studies: cornerstone of design or statistical afterthought?

PubMed

Robinson, John W

2012-03-01

Propensity score models are increasingly used in observational comparative effectiveness studies to reduce confounding by covariates that are associated with both a study outcome and treatment choice. Any such potentially confounding covariate will bias estimation of the effect of treatment on the outcome, unless the distribution of that covariate is well-balanced between treatment and control groups. Constructing a subsample of treated and control subjects who are matched on estimated propensity scores is a means of achieving such balance for covariates that are included in the propensity score model. If, during study design, investigators assemble a comprehensive inventory of known and suspected potentially confounding covariates, examination of how well this inventory is covered by the chosen dataset yields an assessment of the extent of bias reduction that is possible by matching on estimated propensity scores. These considerations are explored by examining the designs of three recently published comparative effectiveness studies.

Homogenization of vegetation structure across residential neighborhoods: effects of climate, urban morphology, and socio-economics

EPA Science Inventory

Climate is a key driver regulating vegetation structure across rural ecosystems. In urban ecosystems, multiple interactions between humans and the environment can have homogenizing influences, confounding the relationship between vegetation structure and climate. In fact, vegetat...

White matter microstructural variability mediates the relation between obesity and cognition in healthy adults.

PubMed

Zhang, Rui; Beyer, Frauke; Lampe, Leonie; Luck, Tobias; Riedel-Heller, Steffi G; Loeffler, Markus; Schroeter, Matthias L; Stumvoll, Michael; Villringer, Arno; Witte, A Veronica

2018-05-15

Obesity has been linked with structural and functional brain changes. However, the impact of obesity on brain and cognition in aging remains debatable, especially for white matter. We therefore aimed to determine the effects of obesity on white matter microstructure and potential implications for cognition in a well-characterized large cohort of healthy adults. In total, 1255 participants (50% females, 19-80 years, BMI 16.8-50.2 kg/m 2 ) with diffusion-weighted magnetic resonance imaging at 3T were analysed. Tract-based spatial statistics (TBSS) probed whether body mass index (BMI) and waist-to-hip ratio (WHR) were related to fractional anisotropy (FA). We conducted partial correlations and mediation analyses to explore whether obesity or regional FA were related to cognitive performance. Analyses were adjusted for demographic, genetic, and obesity-associated confounders. Results showed that higher BMI and higher WHR were associated with lower FA in multiple white matter tracts (p < 0.05, FWE-corrected). Mediation analyses provided evidence for indirect negative effects of higher BMI and higher WHR on executive functions and processing speed through lower FA in fiber tracts connecting (pre)frontal, visual, and associative areas (indirect paths, |ß| ≥ 0.01; 99% |CI| > 0). This large cross-sectional study showed that obesity is correlated with lower FA in multiple white matter tracts in otherwise healthy adults, independent of confounders. Moreover, although effect sizes were small, mediation results indicated that visceral obesity was linked to poorer executive functions and lower processing speed through lower FA in callosal and associative fiber tracts. Longitudinal studies are needed to support this hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Disentangling the developmental trajectories of letter position and letter identity coding using masked priming.

PubMed

Kezilas, Yvette; McKague, Meredith; Kohnen, Saskia; Badcock, Nicholas A; Castles, Anne

2017-02-01

Masked transposed-letter (TL) priming effects have been used to index letter position processing over the course of reading development. Whereas some studies have reported an increase in TL priming over development, others have reported a decrease. These findings have led to the development of 2 somewhat contradictory accounts of letter position development: the lexical tuning hypothesis and the multiple-route model. One factor that may be contributing to these discrepancies is the use of baseline primes that substitute letters in the target word, which may confound the effect of changes in letter position processing over development with those of letter identity. The present study included an identity prime (e.g., listen-LISTEN), in addition to the standard two-substituted-letter (2SL; e.g., lidfen-LISTEN) and all-letter-different (ALD; e.g., rodfup-LISTEN) baselines, to remove the potential confound between letter position and letter identity information in determining the effect of the TL prime. Priming effects were measured in a lexical decision task administered to children aged 7-12 and a group of university students. Using inverse transformed response times, targets preceded by a TL prime were responded to significantly faster than those preceded by 2SL and ALD primes, and priming remained stable across development. In contrast, targets preceded by a TL prime were responded to significantly slower than those preceded by an ID prime, and this reaction-time cost increased significantly over development, with adults showing the largest cost. These findings are consistent with a lexical tuning account of letter position development, and are inconsistent with the multiple-route model. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Association of Total Marine Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acids, With Aortic Stiffness in Koreans, Whites, and Japanese Americans

PubMed Central

2013-01-01

BACKGROUND Few previous studies have reported the association of aortic stiffness with marine n-3 fatty acids (Fas) in the general population. The aim of this study was to determine the combined and independent associations of 2 major marine n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with aortic stiffness evaluated using carotid–femoral pulse wave velocity (cfPWV) in Korean, white, and Japanese American men. METHODS A population-based sample of 851 middle-aged men (299 Koreans, 266 whites, and 286 Japanese Americans) was examined for cfPWV during 2002–2006. Serum FAs, including EPA and DHA, were measured as a percentage of total FAs using gas chromatography. Multiple regression analysis was used to examine the association of EPA and DHA with cfPWV after adjusting for blood pressure and other confounders. RESULTS Mean EPA and DHA levels were 1.9 (SD = 1.0) and 4.8 (SD = 1.4) for Koreans, 0.8 (SD = 0.6) and 2.4 (SD = 1.2) for whites, and 1.0 (SD = 1.0) and 3.2 (SD = 1.4) for Japanese Americans. Both EPA and DHA were significantly higher in Koreans than in the other 2 groups (P < 0.01). Multiple regression analyses in Koreans showed that cfPWV had a significant inverse association with total marine n-3 FAs and with EPA alone after adjusting for blood pressure and other potential confounders. In contrast, there was no significant association of cfPWV with DHA. Whites and Japanese Americans did not show any significant associations of cfPWV with total marine n-3 FAs, EPA, or DHA. CONCLUSIONS High levels of EPA observed in Koreans have an inverse association with aortic stiffness. PMID:23820020

Instrumental variables as bias amplifiers with general outcome and confounding.

PubMed

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

2017-06-01

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

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

PubMed

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

2017-11-01

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

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.

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.

Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation.

PubMed

Szatkiewicz, Jin P; Wang, WeiBo; Sullivan, Patrick F; Wang, Wei; Sun, Wei

2013-02-01

Structural variation is an important class of genetic variation in mammals. High-throughput sequencing (HTS) technologies promise to revolutionize copy-number variation (CNV) detection but present substantial analytic challenges. Converging evidence suggests that multiple types of CNV-informative data (e.g. read-depth, read-pair, split-read) need be considered, and that sophisticated methods are needed for more accurate CNV detection. We observed that various sources of experimental biases in HTS confound read-depth estimation, and note that bias correction has not been adequately addressed by existing methods. We present a novel read-depth-based method, GENSENG, which uses a hidden Markov model and negative binomial regression framework to identify regions of discrete copy-number changes while simultaneously accounting for the effects of multiple confounders. Based on extensive calibration using multiple HTS data sets, we conclude that our method outperforms existing read-depth-based CNV detection algorithms. The concept of simultaneous bias correction and CNV detection can serve as a basis for combining read-depth with other types of information such as read-pair or split-read in a single analysis. A user-friendly and computationally efficient implementation of our method is freely available.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

PubMed Central

2009-01-01

OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex. RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth. PMID:19011170

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.

Adaptive design of visual perception experiments

NASA Astrophysics Data System (ADS)

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

2010-04-01

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

[Evaluative designs in public health: methodological considerations].

PubMed

López, Ma José; Marí-Dell'Olmo, Marc; Pérez-Giménez, Anna; Nebot, Manel

2011-06-01

Evaluation of public health interventions poses numerous methodological challenges. Randomization of individuals is not always feasible and interventions are usually composed of multiple factors. To face these challenges, certain elements, such as the selection of the most appropriate design and the use of a statistical analysis that includes potential confounders, are essential. The objective of this article was to describe the most frequently used designs in the evaluation of public health interventions (policies, programs or campaigns). The characteristics, strengths and weaknesses of each of these evaluative designs are described. Additionally, a brief explanation of the most commonly used statistical analysis in each of these designs is provided. Copyright © 2011 Sociedad Española de Salud Pública y Administración Sanitaria. Published by Elsevier Espana. All rights reserved.

Therapeutic impact of toll-like receptors on inflammatory bowel diseases: a multiple-edged sword.

PubMed

Cario, Elke

2008-03-01

Recent studies have begun to define the mechanisms through which Toll-like receptors (TLRs) regulate intestinal homeostasis in health and disease. Current therapies for inflammatory bowel diseases (IBDs) mostly aim at interrupting the inflammatory cascade through agents that regulate TH1 or TH2 cytokine responses. As recognition grows for TLR dysfunction to play a role in IBD pathogenesis, TLRs could provide another valid interventional target for novel therapy development. However, seemingly contradictory results from studying different murine models of colitis have so far confounded whether therapeutically useful modulation of TLRs is best accomplished by activating, inhibiting, or rather a combination of both at different stages of mucosal disease. This review evaluates potential strategies as well as their rationale and future prospects.

Enacting relationships in marriage and family therapy: a conceptual and operational definition of an enactment.

PubMed

Davis, Sean D; Butler, Mark H

2004-07-01

Enactments are a potential common clinical process factor contributing to positive outcomes in many relational therapies. Enactments provide therapists a medium for mediating relationships through simultaneous experiential intervention and change at multiple levels of relationships--including specific relationship disagreements and problems, interaction process surrounding these issues, and underlying emotions and attachment issues confounded with those problems. We propose a model of enactments in marriage and family therapy, consisting of three components--initiation operations, intervention operations, and evaluation operations. We offer a conceptual framework to help clinicians know when and to what purpose to use this model of enactments. We provide an operational description of each component of an enactment, exemplifying them using a hypothetical clinical vignette. Directions for future research are suggested.

The role of interbasin groundwater transfers in geologically complex terranes, demonstrated by the Great Basin in the western United States

NASA Astrophysics Data System (ADS)

Nelson, Stephen T.; Mayo, Alan L.

2014-06-01

In the Great Basin, USA, bedrock interbasin flow is conceptualized as the mechanism by which large groundwater fluxes flow through multiple basins and intervening mountains. Interbasin flow is propounded based on: (1) water budget imbalances, (2) potential differences between basins, (3) stable isotope evidence, and (4) modeling studies. However, water budgets are too imprecise to discern interbasin transfers and potential differences may exist with or without interbasin fluxes. Potentiometric maps are dependent on conceptual underpinnings, leading to possible false inferences regarding interbasin transfers. Isotopic evidence is prone to non-unique interpretation and may be confounded by the effects of climate change. Structural and stratigraphic considerations in a geologically complex region like the Great Basin should produce compartmentalization, where increasing aquifer size increases the odds of segmentation along a given flow path. Initial conceptual hypotheses should explain flow with local recharge and short flow paths. Where bedrock interbasin flow is suspected, it is most likely controlled by diversion of water into the damage zones of normal faults, where fault cores act as barriers. Large-scale bedrock interbasin flow where fluxes must transect multiple basins, ranges, and faults at high angles should be the conceptual model of last resort.

Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study.

PubMed

Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Kanda, Yoshinobu; Tsugane, Shoichiro

2017-08-01

Background: The aim of this study was to investigate the association of coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan. Methods: In this analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their coffee and green tea consumption were followed up until December 31, 2012, for an average of 18 years. HRs and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders as a measure of association between the risk of malignant lymphoma and multiple myeloma associated with coffee and green tea consumption at baseline. Results: During the follow-up period, a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Overall, our findings showed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma for both sexes. Conclusions: In this study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Impact: Our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers Prev; 26(8); 1352-6. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

Spatial Learning and Wayfinding in an Immersive Environment: The Digital Fulldome.

PubMed

Hedge, Craig; Weaver, Ruth; Schnall, Simone

2017-05-01

Previous work has examined whether immersive technologies can benefit learning in virtual environments, but the potential benefits of technology in this context are confounded by individual differences such as spatial ability. We assessed spatial knowledge acquisition in male and female participants using a technology not previously examined empirically: the digital fulldome. Our primary aim was to examine whether performance on a test of survey knowledge was better in a fulldome (N = 28, 12 males) relative to a large, flat screen display (N = 27, 13 males). Regression analysis showed that, compared to a flat screen display, males showed higher levels of performance on a test of survey knowledge after learning in the fulldome, but no benefit occurred for females. Furthermore, performance correlated with spatial visualization ability in male participants, but not in female participants. Thus, the digital fulldome is a potentially useful learning aid, capable of accommodating multiple users, but individual differences and use of strategy need to be considered.

The time course of symbolic number adaptation: oscillatory EEG activity and event-related potential analysis.

PubMed

Hsu, Yi-Fang; Szűcs, Dénes

2012-02-15

Several functional magnetic resonance imaging (fMRI) studies have used neural adaptation paradigms to detect anatomical locations of brain activity related to number processing. However, currently not much is known about the temporal structure of number adaptation. In the present study, we used electroencephalography (EEG) to elucidate the time course of neural events in symbolic number adaptation. The numerical distance of deviants relative to standards was manipulated. In order to avoid perceptual confounds, all levels of deviants consisted of perceptually identical stimuli. Multiple successive numerical distance effects were detected in event-related potentials (ERPs). Analysis of oscillatory activity further showed at least two distinct stages of neural processes involved in the automatic analysis of numerical magnitude, with the earlier effect emerging at around 200ms and the later effect appearing at around 400ms. The findings support for the hypothesis that numerical magnitude processing involves a succession of cognitive events. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Health-Related Behavior Mediates the Association Between Personality and Memory Performance in Older Adults.

PubMed

Allen, Mark S; Laborde, Sylvain; Walter, Emma E

2017-03-01

This prospective study explored the potential mediating role of health-related behavior (alcohol involvement, diet, television viewing, and physical activity) in the association between personality and change in memory performance over 2 years. A nationally representative sample of 8,376 U.K. participants aged 55 years and older (4,572 women, 3,804 men) completed self-report measures of personality and health-related behavior in 2010, and completed a memory performance task in 2010 and 2012. After removing variance associated with potential confounding variables, neuroticism and agreeableness had negative associations, and openness and conscientiousness positive associations with change in memory performance. There were no moderation effects by age, sex, education level, or ethnicity. Multiple mediator models demonstrated that physical activity, television viewing, and alcohol intake mediated associations between personality and change in memory performance. These findings provide evidence that the association between personality and memory performance in older adults can be explained, in part, through health-related behavior.

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

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

PubMed

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

2004-05-01

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

SELECTING LEAST-DISTURBED SURVEY SITES FOR GREAT PLAINS STREAMS AND RIVERS

EPA Science Inventory

True reference condition probably does not exist for streams in highly utilized regions such as the Great Plains. Selecting least-disturbed sites for large regions is confounded by the association between human uses and natural gradients, and by multiple kinds of disturbance. U...

Use of a quality trait index to increase the reliability of phenotypic evaluations in broccoli

USDA-ARS?s Scientific Manuscript database

Selection of superior broccoli hybrids involves multiple considerations, including optimization of head quality traits. Quality assessment of broccoli heads is often confounded by relatively subjective human preferences for optimal appearance of heads. To assist the selection process, we assessed fi...

Smartberries: Interpreting Erdrich's Love Medicine

ERIC Educational Resources Information Center

Treuer, David

2005-01-01

The structure of "Love Medicines" interpreted by Hertha D. Sweet Wong who claims that the book's "multiple narrators confound conventional Western expectations of an autonomous protagonist, a dominant narrative voice, and a consistently chronological narrative". "Love Medicine" is a brilliant use of the Western literary tactics that create the…

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

PubMed

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

2012-05-01

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

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

PubMed

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

2016-10-13

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

Estimating the monetary value of willingness to pay for E-book reader's attributes using partially confounded factorial conjoint choice experiment

NASA Astrophysics Data System (ADS)

Yong, Chin-Khian

2013-09-01

A partially confounded factorial conjoint choice experiments design was used to examine the monetary value of the willingness to pay for E-book Reader's attributes. Conjoint analysis is an efficient, cost-effective, and most widely used quantitative method in marketing research to understand consumer preferences and value trade-off. Value can be interpreted by customer or consumer as the received of multiple benefits from a price that was paid. The monetary value of willingness to pay for battery life, internal memory, external memory, screen size, text to Speech, touch screen, and converting handwriting to digital text of E-book reader were estimated in this study. Due to the significant interaction effect of the attributes with the price, the monetary values for the seven attributes were found to be different at different values of odds of purchasing versus not purchasing. The significant interactions effects were one of the main contribution of the partially confounded factorial conjoint choice experiment.

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus.

PubMed

Ng, D P K; Salim, A; Liu, Y; Zou, L; Xu, F G; Huang, S; Leong, H; Ong, C N

2012-02-01

We carried out a urinary metabolomic study to gain insight into low estimated GFR (eGFR) in patients with non-proteinuric type 2 diabetes. Patients were identified as being non-proteinuric using multiple urinalyses. Cases (n = 44) with low eGFR and controls (n = 46) had eGFR values <60 and ≥60 ml min(-1) 1.73 m(-2), respectively, as calculated using the Modification of Diet in Renal Disease formula. Urine samples were analysed by liquid chromatography/mass spectrometry (LC/MS) and GC/MS. False discovery rates were used to adjust for multiple hypotheses testing, and selection of metabolites that best predicted low eGFR status was achieved using least absolute shrinkage and selection operator logistic regression. Eleven GC/MS metabolites were strongly associated with low eGFR after correction for multiple hypotheses testing (smallest adjusted p value = 2.62 × 10(-14), largest adjusted p value = 3.84 × 10(-2)). In regression analysis, octanol, oxalic acid, phosphoric acid, benzamide, creatinine, 3,5-dimethoxymandelic amide and N-acetylglutamine were selected as the best subset for prediction and allowed excellent classification of low eGFR (AUC = 0.996). In LC/MS, 19 metabolites remained significant after multiple hypotheses testing had been taken into account (smallest adjusted p value = 2.04 × 10(-4), largest adjusted p value = 4.48 × 10(-2)), and several metabolites showed stronger evidence of association relative to the uraemic toxin, indoxyl sulphate (adjusted p value = 3.03 × 10(-2)). The potential effect of confounding on the association between metabolites was excluded. Our study has yielded substantial new insight into low eGFR and provided a collection of potential urinary biomarkers for its detection.

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

PubMed

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

2016-10-01

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

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

PubMed

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

2018-04-01

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

When can the cause of a population decline be determined?

PubMed

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

2016-11-01

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

When can the cause of a population decline be determined?

USGS Publications Warehouse

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

2016-01-01

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

Multiple imputation to evaluate the impact of an assay change in national surveys

PubMed Central

Sternberg, Maya

2017-01-01

National health surveys, such as the National Health and Nutrition Examination Survey, are used to monitor trends of nutritional biomarkers. These surveys try to maintain the same biomarker assay over time, but there are a variety of reasons why the assay may change. In these cases, it is important to evaluate the potential impact of a change so that any observed fluctuations in concentrations over time are not confounded by changes in the assay. To this end, a subset of stored specimens previously analyzed with the old assay is retested using the new assay. These paired data are used to estimate an adjustment equation, which is then used to ‘adjust’ all the old assay results and convert them into ‘equivalent’ units of the new assay. In this paper, we present a new way of approaching this problem using modern statistical methods designed for missing data. Using simulations, we compare the proposed multiple imputation approach with the adjustment equation approach currently in use. We also compare these approaches using real National Health and Nutrition Examination Survey data for 25-hydroxyvitamin D. PMID:28419523

Arithmetic memory networks established in childhood are changed by experience in adulthood

PubMed Central

Martinez-Lincoln, Amanda; Cortinas, Christina; Wicha, Nicole Y. Y.

2014-01-01

Adult bilinguals show stronger access to multiplication tables when using the language in which they learned arithmetic during childhood (LA+) than the other language (LA−), implying language-specific encoding of math facts. However, most bilinguals use LA+ throughout their life, confounding the impact of encoding and use. We tested if using arithmetic facts in LA− could reduce this LA− disadvantage. We measured event related brain potentials while bilingual teachers judged the correctness of multiplication problems in each of their languages. Critically, each teacher taught arithmetic in either LA+ or LA−. Earlier N400 peak latency was observed in both groups for the teaching than non-teaching language, showing more efficient access to these facts with use. LA+ teachers maintained an LA+ advantage, while LA− teachers showed equivalent N400 congruency effects (for incorrect versus correct solutions) in both languages. LA− teachers also showed a late positive component that may reflect conflict monitoring between their LA+ and a strong LA−. Thus, the LA− disadvantage for exact arithmetic established in early bilingual education can be mitigated by later use of LA−. PMID:25445361

A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data.

PubMed

Spelman, Tim; Gray, Orla; Lucas, Robyn; Butzkueven, Helmut

2015-12-09

This report describes a novel Stata-based application of trigonometric regression modelling to 55 years of multiple sclerosis relapse data from 46 clinical centers across 20 countries located in both hemispheres. Central to the success of this method was the strategic use of plot analysis to guide and corroborate the statistical regression modelling. Initial plot analysis was necessary for establishing realistic hypotheses regarding the presence and structural form of seasonal and latitudinal influences on relapse probability and then testing the performance of the resultant models. Trigonometric regression was then necessary to quantify these relationships, adjust for important confounders and provide a measure of certainty as to how plausible these associations were. Synchronization of graphing techniques with regression modelling permitted a systematic refinement of models until best-fit convergence was achieved, enabling novel inferences to be made regarding the independent influence of both season and latitude in predicting relapse onset timing in MS. These methods have the potential for application across other complex disease and epidemiological phenomena suspected or known to vary systematically with season and/or geographic location.

A prospective-longitudinal study on the association of anxiety disorders prior to pregnancy and pregnancy- and child-related fears.

PubMed

Martini, Julia; Asselmann, Eva; Einsle, Franziska; Strehle, Jens; Wittchen, Hans-Ulrich

2016-05-01

This study aimed to investigate the relation between anxiety disorders prior to pregnancy and specific pregnancy- and child-related fears during pregnancy and after delivery. 306 expectant mothers were interviewed regarding anxiety (and depressive) disorders prior to pregnancy and pregnancy- and child-related fears (e.g. fear of labor pain, fear of infant injury) using the Composite International Diagnostic Interview for Women (CIDI-V). Pregnancy- and child-related fears were particularly pronounced in women with multiple anxiety disorders and women with comorbid anxiety and depressive disorders prior to pregnancy. Further analyses revealed associations between particular anxiety disorders and specific pregnancy- and child-related fears. Results remained stable when considering potential confounders such as maternal age, education, marital status, parity, prior abortion and preterm delivery or low birth weight. Our study suggests that especially women with multiple anxiety and/or comorbid depressive disorders may benefit from early targeted interventions to prevent an escalation of anxiety and fears over the peripartum period. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-04-01

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

War-related trauma exposure and multiple risk behaviors among school-going adolescents in Northern Uganda: the mediating role of depression symptoms.

PubMed

Okello, James; Nakimuli-Mpungu, Etheldreda; Musisi, Seggane; Broekaert, Eric; Derluyn, Ilse

2013-11-01

The relationship between war-related trauma exposure, depressive symptoms and multiple risk behaviors among adolescents is less clear in sub-Saharan Africa. We analyzed data collected from a sample of school-going adolescents four years postwar. Participants completed interviews assessing various risk behaviors defined by the Youth Self Report (YSR) and a sexual risk behavior survey, and were screened for post-traumatic stress, anxiety and depression symptoms based on the Impact of Events Scale Revised (IESR) and Hopkins Symptom Checklist for Adolescents (HSCL-37A) respectively. Multivariate logistic regression was used to assess factors independently associated with multiple risk behaviors. The logistic regression model of Baron and Kenny (1986) was used to evaluate the mediating role of depression in the relationship between stressful war events and multiple risk behaviors. Of 551 participants, 139 (25%) reported multiple (three or more) risk behaviors in the past year. In the multivariate analyses, depression symptoms remained uniquely associated with multiple risk behavior after adjusting for potential confounders including socio-demographic characteristics, war-related trauma exposure variables, anxiety and post-traumatic stress symptoms. In mediation analysis, depression symptoms mediated the associations between stressful war events and multiple risk behaviors. The psychometric properties of the questionnaires used in this study are not well established in war affected African samples thus ethno cultural variation may decrease the validity of our measures. Adolescents with depression may be at a greater risk of increased engagement in multiple risk behaviors. Culturally sensitive and integrated interventions to treat and prevent depression among adolescents in post-conflict settings are urgently needed. © 2013 Elsevier B.V. All rights reserved.

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

Treesearch

Samuel A. Cushman; Kevin McGarigal

2004-01-01

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

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

PubMed

Keller, Matthew C

2014-01-01

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

Identifying patterns of general practitioner service utilisation and their relationship with potentially preventable hospitalisations in people with diabetes: The utility of a cluster analysis approach.

PubMed

Ha, Ninh Thi; Harris, Mark; Preen, David; Robinson, Suzanne; Moorin, Rachael

2018-04-01

We aimed to characterise use of general practitioners (GP) simultaneously across multiple attributes in people with diabetes and examine its impact on diabetes related potentially preventable hospitalisations (PPHs). Five-years of panel data from 40,625 adults with diabetes were sourced from Western Australian administrative health records. Cluster analysis (CA) was used to group individuals with similar patterns of GP utilisation characterised by frequency and recency of services. The relationship between GP utilisation cluster and the risk of PPHs was examined using multivariable random-effects negative binomial regression. CA categorised GP utilisation into three clusters: moderate; high and very high usage, having distinct patient characteristics. After adjusting for potential confounders, the rate of PPHs was significantly lower across all GP usage clusters compared with those with no GP usage; IRR = 0.67 (95%CI: 0.62-0.71) among the moderate, IRR = 0.70 (95%CI 0.66-0.73) high and IRR = 0.76 (95%CI 0.72-0.80) very high GP usage clusters. Combination of temporal factors with measures of frequency of use of GP services revealed patterns of primary health care utilisation associated with different underlying patient characteristics. Incorporation of multiple attributes, that go beyond frequency-based approaches may better characterise the complex relationship between use of GP services and diabetes-related hospitalisation. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Tehran Survey of Potential Risk Factors for Multiple Births.

PubMed

Omani Samani, Reza; Almasi-Hashiani, Amir; Vesali, Samira; Shokri, Fatemeh; Cheraghi, Rezvaneh; Torkestani, Farahnaz; Sepidarkish, Mahdi

2017-10-01

The multiple pregnancy incidence is increasing worldwide. This increased incidence is concerning to the health care system. This study aims to determine the frequency of multiple pregnancy and identify factors that affect this frequency in Tehran, Iran. This cross-sectional study included 5170 mothers in labor between July 6-21, 2015 from 103 hospitals with Obstetrics and Gynecology Wards. The questionnaire used in this study consisted of five parts: demographic characteristics; information related to pregnancy; information related to the infant; information regarding the multiple pregnancy; and information associated with infertility. We recruited 103 trained midwives to collect data related to the questionnaire from eligible participants through an interview and medical records review. Frequencies and odds ratios (OR) for the association between multiple pregnancy and the selected characteristics (maternal age, economic status, history of multiple pregnancy in first-degree relatives, and reproductive history) were computed by multiple logistic regression. Stata software, version 13 (Stata Corp, College Station, TX, USA) was used for all statistical analyses. Multiple pregnancy had a prevalence of 1.48% [95% confidence interval (CI): 1.19-1.85]. After controlling for confounding variables, we observed a significant association between frequency of multiple pregnancy and mother's age (OR=1.04, 95% CI: 1.001-1.09, P=0.044), assisted reproductive technique (ART, OR=6.11, 95% CI: 1.7- 21.97, P=0.006), and history of multiple pregnancy in the mother's family (OR=5.49, 95% CI: 3.55-9.93, P=0.001). The frequency of multiple pregnancy approximated results reported in previous studies in Iran. Based on the results, we observed significantly greater frequency of multiple pregnancy in older women, those with a history of ART, and a history of multiple pregnancy in the mother's family compared to the other variables. Copyright© by Royan Institute. All rights reserved.

A case control study of multiple myeloma at four nuclear facilities.

PubMed

Wing, S; Richardson, D; Wolf, S; Mihlan, G; Crawford-Brown, D; Wood, J

2000-04-01

Reported elevations of multiple myeloma among nuclear workers exposed to external penetrating ionizing radiation, based on small numbers of cases, prompted this multi-facility study of workers at US Department of Energy facilities. Ninety-eight multiple myeloma deaths and 391 age-matched controls were selected from the combined roster of 115,143 workers hired before 1979 at Hanford, Los Alamos National Laboratory, Oak Ridge National Laboratory, and the Savannah River site. These workers were followed for vital status through 1990 (1986 for Hanford). Demographic, work history, and occupational exposure data were derived from personnel, occupational medicine, industrial hygiene, and health physics records. Exposure-disease associations were evaluated using conditional logistic regression. Cases were disproportionately African American, male, and hired prior to 1948. Lifetime cumulative whole body ionizing radiation dose was not associated with multiple myeloma, however, there was a significant effect of age at exposure, with positive associations between multiple myeloma and doses received at older ages. Dose response associations increased in magnitude with exposure age (from 40 to 50) and lag assumption (from 5 to 15 years), while a likelihood ratio goodness of fit test reached the highest value for cumulative doses received at ages above 45 with a 5-year lag (X2=5.43,1 df; relative risk = 6.9% per 10 mSv). Dose response associations persisted with adjustment for potential confounders. Multiple myeloma was associated with low level whole body penetrating ionizing radiation doses at older ages. The exposure age effect is at odds with interpretations of A-bomb survivor studies but in agreement with several studies of cancer among nuclear workers.

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

PubMed

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

2016-10-01

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

"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.

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.

A seroprevalence and descriptive epidemiological study of malaria among Indian tribes of the Amazon basin of Brazil.

PubMed

de Arruda, M E; Aragaki, C; Gagliardi, F; Haile, R W

1996-04-01

Data on the seroprevalences of Plasmodium falciparum, P. vivax, and P. malariae in four isolated Indian tribes of the Amazon basin in Brazil, as determined by IFAT, were re-analysed. Age-, sex- and tribe-specific geometric mean antibody titres and externally standardized prevalence ratios were calculated for each parasite species. Correlation coefficients and prevalence odds ratios were also calculated for multiple infections with different combinations of the three Plasmodium species. Titres of all but one of the antibodies studied were similar in males and females; titres of antibodies to the blood stages of P. malariae were slightly higher in females than in males. Titres of antibodies to all three Plasmodium species increased with subject age, and this age effect was not confounded by sex or tribal differences. There were striking differences between tribes, with the Parakana tribe having relatively low titres of antibodies against P. falciparum and P. malariae; these tribal effects were not confounded by sex or age differences between tribes. The results indicate that conditions conductive to the transmission of P. malariae exist in this region of the Amazon. The potential for zoonotic transmission of P. brasilianum, a parasite of monkeys which is morphologically similar to P. malarie, and the generally high rates of seropositivity to all three species of Plasmodium indicate that control measures which are adequate and applicable to the region studied need to be developed.

Recruitment factors which affect the outcome of a seasonal allergic rhinitis trial.

PubMed

Sharma, Shilpy; Vasnani, Raj; De Tineo, Marcella; Du, Gaixin; Pinto, Jayant M; Baroody, Fuad M; Naclerio, Robert M

2011-01-01

Although intranasal corticosteroids (INSs) are the first-line treatment for seasonal allergic rhinitis (SAR), some patients do not respond adequately, reflecting biological heterogeneity or confounding conditions. The objective of this study was to determine what recruitment factors identify SAR subjects who will be unresponsive to mometasone furoate (MF). We performed a 2-week, double-blind, placebo-controlled, parallel study on 40 subjects with SAR. Each subject underwent a decongestant test using oxymetazoline. Baseline nasal symptoms, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were recorded. Next, subjects were randomized to either 200 μg of MF or placebo. Symptom diaries and NPIF measurements were completed twice daily. After 2 weeks, subjects repeated the RQLQ and the global assessment of symptoms. There was a significant reduction in symptoms in the MF group compared with placebo (p ≤ 0.05) in patients with baseline total symptom scores of ≥6. Multivariate analysis showed that treatment (MF versus placebo; p = 0.049) and amount of decongestion (percent change in NPIF after oxymetazoline; p = 0.008) predicted the improvement in total nasal symptoms. In clinical trials, SAR subjects must report multiple symptoms to be responsive to treatment with INSs. Our results also support the use of the decongestant test for choice of appropriate study volunteers, both to ensure participation of potentially responsive subjects and to eliminate those with confounding issues.

Visualization and dissemination of multidimensional proteomics data comparing protein abundance during Caenorhabditis elegans development.

PubMed

Riffle, Michael; Merrihew, Gennifer E; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N; Noble, William S; MacCoss, Michael J

2015-11-01

Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/ . Graphical Abstract ᅟ.

Visualization and Dissemination of Multidimensional Proteomics Data Comparing Protein Abundance During Caenorhabditis elegans Development

NASA Astrophysics Data System (ADS)

Riffle, Michael; Merrihew, Gennifer E.; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N.; Noble, William S.; MacCoss, Michael J.

2015-11-01

Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/.

Clinical uses of brain natriuretic peptide in diagnosing and managing heart failure.

PubMed

Anderson, Kelley M

2008-06-01

To review current issues in the diagnosis, prognosis, and management of heart failure (HF), focusing on the clinical use of brain natriuretic peptide (BNP) as a diagnostic marker. Selective review of scientific literature and clinical practice guidelines. BNP is a useful clinical tool for the diagnosis, prognosis, and management of HF patients. Studies have consistently demonstrated high sensitivity, specificity, and negative predictive value of BNP levels in diagnostic situations. BNP cannot differentiate between systolic and diastolic HF. BNP can be used to assist in diagnosing HF in emergency and outpatient situations, particularly when the presenting symptom is dyspnea; determining HF prognosis, including predicting death and cardiac events; and potentially managing individuals with HF by determining safe discharge levels from acute care to avoid readmissions. BNP levels can vary depending on multiple confounders; therefore, clinical interpretation can be difficult.

Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study.

PubMed

Houston, Denise K; Nicklas, Barbara J; Ding, Jingzhong; Harris, Tamara B; Tylavsky, Frances A; Newman, Anne B; Lee, Jung Sun; Sahyoun, Nadine R; Visser, Marjolein; Kritchevsky, Stephen B

2008-01-01

Dietary surveys suggest that many older, community-dwelling adults consume insufficient dietary protein, which may contribute to the age-related loss of lean mass (LM). The objective of the study was to determine the association between dietary protein and changes in total LM and nonbone appendicular LM (aLM) in older, community-dwelling men and women. Dietary protein intake was assessed by using an interviewer-administered 108-item food-frequency questionnaire in men and women aged 70-79 y who were participating in the Health, Aging, and Body Composition study (n=2066). Changes in LM and aLM over 3 y were measured by using dual-energy X-ray absorptiometry. The association between protein intake and 3-y changes in LM and aLM was examined by using multiple linear regression analysis adjusted for potential confounders. After adjustment for potential confounders, energy-adjusted protein intake was associated with 3-y changes in LM [beta (SE): 8.76 (3.00), P=0.004] and aLM [beta (SE): 5.31 (1.64), P=0.001]. Participants in the highest quintile of protein intake lost approximately 40% less LM and aLM than did those in the lowest quintile of protein intake (x+/-SE: -0.501+/-0.106 kg compared with -0.883+/-0.104 kg for LM; -0.400+/-0.058 kg compared with -0.661+/-0.057 kg for aLM; P for trend<0.01). The associations were attenuated slightly after adjustment for change in fat mass, but the results remained significant. Dietary protein may be a modifiable risk factor for sarcopenia in older adults and should be studied further to determine its effects on preserving LM in this population.

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

PubMed

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

2018-05-01

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

Prevalent involvement of thenar motor fibres in vineyard workers with carpal tunnel syndrome.

PubMed

Mondelli, M; Baldasseroni, A; Aretini, A; Ginanneschi, F; Padua, L

2010-08-01

Carpal tunnel syndrome (CTS) has a high prevalence in agricultural workers, especially those engaged in vineyards. We postulated that vineyard CTS was electrophysiologically different from CTS of other subjects. We performed a retrospective cross-sectional electrophysiological study of two cohorts of consecutive patients with CTS, the first consisting of vineyard workers and the second, of other unselected types of workers, housewives and pensioners. Thirty-three vineyard workers (mean age 46.8years, 42% women) and 205 patients with other occupations (mean age 53.7years; 66% women) were enrolled. All patients underwent sensory and motor neurography of the median and ulnar nerves. Differences in demographic and electrophysiological findings between groups were calculated and multiple linear regression analysis was performed to eliminate the influence of potential confounding factors (age, sex, BMI, clinical severity of CTS) on the results of univariate difference analysis. Univariate analysis showed that DML was longer and compound muscle action potential amplitude of the median nerve, recorded from the abductor pollicis brevis muscle, was smaller in vineyard workers than in the other CTS patients. These differences remained significant after adjusting the results for confounding factors. The vineyard workers showed a different pattern of CTS than the other patients: thenar motor fibres were more affected, presumably due to chronic compression on the thenar branch. This suggests an association between "common" CTS and thenar mononeuropathy. Occupational physiologists should clarify the mechanisms of neuromuscular engagement in particular jobs and ergonomists design suitable working tools, because many "individual" risk factors are difficult to change, but workplace-related risk factors can be modified. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of Exposure to Air Pollution on Placental Weight in Isfahan-Iran.

PubMed

Ghasemi-Tehrani, Hatav; Fallah, Setare; Mozafarian, Nafiseh; Miranzadeh, Sareh; Sadeghi, Shokooh; Azidhak, Azam

2017-06-01

Objective: To determine the effect of Air Quality Index (AQI) in the first trimester of pregnancy on birth weight, placental weight, and the ratio of placental weight to the birth weight (pw-bw) in Isfahan. Materials and methods: This cross-sectional study was done on 312 consecutive pregnant women in Beheshti Hospital in Isfahan city in 2013. Information on air pollution was received from the Environmental department of Isfahan. Average exposure to air pollution in the first trimester of pregnancy was calculated for eachpregnant woman. In order to compare quantitative and qualitative variables, analysis of variance (ANOVA), and chi-square were applied. After that, the multiple linear regression analysis was used to assess the association the Air Quality Index (AQI) on birth weight, placental weight and the ratio of pw-bw. Potential confounders including age, baby gender, smoking of husband, maternal BMI, maternal occupation, and education and mother's residential area were considered. A statistical significant association were considered for P-value less than 0.05. Results: The findings showed that there is inverse relationship between exposure to air pollution and placental weight in the first trimester of pregnancy after controlling potential confounders (β = -2.57, p-value = 0.008). The inverse relationship between air pollution and the ratio of pw-bw was found. (β = -0.001, p-value = 0.002). Conclusion: The results of this study suggest that air pollution is associated with newborns' health which in turn is a warning alarm for considering some actions in both sides of reducing the air pollution and teaching the pregnant women about the adverse effects of air pollution on the pregnancy outcomes.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

PubMed

Murphy, Kellie E; Willan, Andrew R; Hannah, Mary E; Ohlsson, Arne; Kelly, Edmond N; Matthews, Stephen G; Saigal, Saroj; Asztalos, Elizabeth; Ross, Susan; Delisle, Marie-France; Amankwah, Kofi; Guselle, Patricia; Gafni, Amiram; Lee, Shoo K; Armson, B Anthony

2012-05-01

To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. II.

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.

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

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

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

Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines?

PubMed Central

Malekzadeh, Arjan; Van de Geer-Peeters, Wietske; De Groot, Vincent; Elisabeth Teunissen, Charlotte; Beckerman, Heleen; TREFAMS-ACE Study Group

2015-01-01

Objective. To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue. Methods. Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue ≤34) and fatigued (CIS20r fatigue ≥35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs. Results. Similar cytokine levels were observed between MS patients with (n = 21) and without fatigue (n = 14). Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age. Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS. Trial Registrations. ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628. PMID:25722532

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.

An Evidence-Based Approach to an Adolescent with Emotional and Behavioral Dysregulation

ERIC Educational Resources Information Center

McClellan, Jon M.; Hamilton, John D.

2006-01-01

Children and adolescents in community mental health settings often present with multiple overlapping syndromes, as well as confounding issues such as family turmoil, abuse and neglect, and involvement with social welfare and juvenile justice systems. Most interventions proven to have efficacy in randomized, controlled trials have nevertheless not…

Learning and Motivational Benefits of Acronym Use in Introductory Psychology

ERIC Educational Resources Information Center

Stalder, Daniel R.

2005-01-01

Study 1 assessed students' use and perceptions of acronyms at 3 different exam times in 2 sections of Introduction to Psychology. Acronym use consistently predicted higher performance on acronym related exam items, and I partially discounted 2 possible confounds. Students rated acronyms as helpful in multiple ways, including increasing motivation…

Vertebral hemangiomas in the thoracic spine of multiple sclerosis patients are connected with fewer demyelinating lesions at the same level. Possible impact on pathophysiology and clinical course.

PubMed

Anagnostouli, Maria; Katsavos, Serafeim; Kyrozis, Andreas; Gontika, Maria; Voumvourakis, Konstantinos I; Kapaki, Elisabeth

2016-08-01

Mechanisms of angiogenesis regulate multiple sclerosis (MS) lesions' evolution, displaying both neuroprotective and harmful effects. Factors traditionally considered as purely angiogenic, like vascular endothelial growth factor (VEGF), exert complex heterogenous actions on both neural and vascular malformation-derived tissues. Aim of this retrospective study was to examine, for the first time, potential associations between the presence of common vascular malformations, like vertebral hemangiomas (VHs), and several clinico-radiological MS parameters. 236 MS patients who were followed in our Outpatient Clinic were recruited in this study. Outcome measures concerned demographics, disease-derived variables, and MS-lesions' distribution in VHs - positive and negative patients. All data were collected retrospectively. Potential correlations were assessed with univariate statistical analyses (p = 0.05), followed by multivariate regression models, for purposes of confounder-effects elimination. VH presence showed significant negative correlations with presence of MS lesions in the thoracic (p = 0.005 for thoracic VHs), but not the cervical cord. Trends towards negative associations of VH presence with subtentorial MS lesions and positive family history for MS were also observed. Our observations suggest that VH presence may reduce the risk of thoracic demyelinating lesions in MS patients. They could be explained as part of a multifaceted angiogenic process, concomitantly enhancing neural repair and abnormal hemangioma vascularization.

Potential for effects of land contamination on human health. 2. The case of waste disposal sites.

PubMed

Kah, Melanie; Levy, Len; Brown, Colin

2012-01-01

This review of the epidemiological literature shows that evidence for negative impacts of land contaminated by waste disposal on human health is limited. However, the potential for health impacts cannot be dismissed. The link between residence close to hazardous waste disposal sites and heightened levels of stress and anxiety is relatively well established. However, studies on self-reported outcomes generally suffer from interpretational problems, as subjective symptoms may be due to increased perception and recall. Several recent multiple-site studies support a plausible linkage between residence near waste disposal sites and reproductive effects (including congenital anomalies and low birth weight). There is some conflict in the literature investigating links between land contamination and cancers; the evidence for and against a link is equally balanced and is insufficient to make causal inferences. These are difficult to establish because of lack of data on individual exposures, and other socioeconomic and lifestyle factors that may confound a relationship with area of residence. There is no consistently occurring risk for any specific tumor across multiple studies on sites expected to contain similar contaminants. Further insights on health effects of land contamination are likely to be gained from studies that consider exposure pathways and biomarkers of exposure and effect, similar to those deployed with some success in investigating impacts of cadmium on human health.

Doubly robust matching estimators for high dimensional confounding adjustment.

PubMed

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

2018-05-11

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

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

USGS Publications Warehouse

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

2015-01-01

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

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.

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.

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.

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

Thyroid STAtus and 6-Year Mortality in Elderly People Living in a Mildly Iodine-Deficient Area: The Aging in the Chianti Area (InCHIANTI) Study

PubMed Central

Ceresini, Graziano; Ceda, Gian Paolo; Lauretani, Fulvio; Maggio, Marcello; Usberti, Elisa; Marina, Michela; Bandinelli, Stefania; Guralnik, Jack M.; Valenti, Giorgio; Ferrucci, Luigi

2013-01-01

Objectives The relationship between thyroid dysfunction and mortality in elderly subjects is still undefined. In this population study we tested the hypothesis that in older subjects, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with increased mortality independent of potential confounders. Design Longitudinal study Setting Community-based Participants Total of 951 subjects aged 65 years and older Measurements Plasma thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations and demographic features were evaluated in participants of the Aging in the Chianti Area (InCHIANTI) study, aged 65 years or older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results A total of 819 participants were euthyroid, 83 had Subclinical hyperthyroidism (SHyper), and 29 had Subclinical hypothyroidism (SHypo). Overt Hypo- and Hyperthyroidism were found in 5 and 15 subjects, respectively. During a median of six-years of follow-up, N 210 deaths occurred (22.1 %) of which 98 (46.6%) due to cardiovascular causes. Kaplan–Meier analysis revealed higher overall mortality for SHyper (P<0.04) as compared to euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (Hazard Ratio[HR]:1.65; 95% Confidence Interval [CI]: 1.02–2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality. In euthyroid subjects, TSH was found to be predictive of a reduced risk of all-cause mortality (HR: 0.76; 95% CI, 0.57–0.99) Conclusion SHyper is an independent risk factor for all-cause mortality in the older population. Low-normal circulating TSH should be carefully monitored in euthyroid elderly individuals. PMID:23647402

Low cardiorespiratory fitness in young adulthood and future risk of disability pension: a follow-up study until 59 years of age in Swedish men.

PubMed

Rabiee, Rynaz; Agardh, Emilie; Kjellberg, Katarina; Falkstedt, Daniel

2015-03-01

There is a strong belief in the potential of increased physical activity to improve the health of populations. The objective of the present study was to estimate the association between low cardiorespiratory fitness in young adulthood and subsequent health impairment until middle age, measured by disability pension. The study utilised data on cardiorespiratory fitness and a number of covariates (social background, health behaviours and psychological characteristics) from the Swedish Conscription Cohort of 1969/1970 including 49,321 men born in 1949-1951, and data on disability pension from 1971 to 2008 (20-59 years of age) through record linkage with two national insurance databases. Cox proportional-hazards regressions yielded hazard ratios (HR) with 95% confidence intervals (CI). Having low-level or mid-level cardiorespiratory fitness in late adolescence was associated with an increased HR of disability pension across the follow-up (HR for low fitness: 1.85, CI 1.71 to 2.00; HR for mid-level fitness: 1.40, CI 1.31 to 1.50). The association was stronger with earlier disability pensions than with later disability pensions, which was also seen after multiple confounding adjustments. At the same time, these adjustments revealed considerable confounding of the association by individual differences in psychological characteristics in particular. Lower levels of cardiorespiratory fitness in young adulthood were found to be associated with an increased HR of disability pension throughout the follow-up until 59 years of age, even after adjustment for important confounding factors measured in late adolescence. Increased physical fitness may thus have a lowering effect on the risk of disability pension. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Multiple roles and all-cause mortality: the Japan Collaborative Cohort Study.

PubMed

Tamakoshi, Akiko; Ikeda, Ai; Fujino, Yoshihisa; Tamakoshi, Koji; Iso, Hisoyasu

2013-02-01

Two contrasting perspectives on the effects of multiple roles; the 'role overload hypothesis' and the 'role enhancement model', have been proposed to predict variations in health. The aim of this study was to evaluate the impact of multiple roles on all-cause mortality in Japan where gender roles are currently changing. A total of 76,758 individuals from the Japan Collaborative Cohort Study were followed for an average of 15.7 years. Hazard ratios (HRs) with 95% confidence intervals were calculated from proportional hazard models to estimate the risk of all-cause mortality according to multiple roles (spouse, parent and worker, and combinations of these roles). After adjusting for potential confounding factors, the risks of all-cause mortality were elevated among men and women without a role. The number of roles was also associated with all-cause mortality risk, showing the highest risk values among those with no roles compared with those with triple roles (HR: 1.66 in men and 1.78 in women). The impact of the lack of a role was generally greater in men than in women and also in the middle-aged than in the elderly. A beneficial effect of multiple roles was suggested among Japanese. The fewer roles they had, the higher all-cause mortality risks were observed. The risk values of those with fewer roles were generally higher in men than in women and also in the middle-aged than in the elderly, partially explained by greater role overload in middle-aged women than other groups in Japan.

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

Clinical Research Methodology 2: Observational Clinical Research.

PubMed

Sessler, Daniel I; Imrey, Peter B

2015-10-01

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

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage.

PubMed

Hurd, Yasmin L; Yoon, Michelle; Manini, Alex F; Hernandez, Stephanie; Olmedo, Ruben; Ostman, Maria; Jutras-Aswad, Didier

2015-10-01

Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ(9)-tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from "medical CBD" and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

Action potential propagation recorded from single axonal arbors using multi-electrode arrays.

PubMed

Tovar, Kenneth R; Bridges, Daniel C; Wu, Bian; Randall, Connor; Audouard, Morgane; Jang, Jiwon; Hansma, Paul K; Kosik, Kenneth S

2018-04-11

We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multi-electrode arrays (MEAs). The invariant sequences of eAPs among co-active electrode groups, repeated co-occurrences and short inter-electrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP co-detection by multiple electrodes was widespread in all our data records. Co-detection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among co-active electrodes 'fingerprints' neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the non-invasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low electrode density MEAs. However, repeated eAP co-occurrences leads to over-sampling spikes from single neurons and thus can confound traditional spike-train analysis.

Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment.

PubMed

Yegin, Ender Gunes; Oymaci, Erkan; Karatay, Emrah; Coker, Ahmet

2016-06-01

Hepatocellular carcinoma (HCC) is a complex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple confounding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortality globally with a rising trend of incidence in some of the developed countries, which indicates the need for better surgical and nonsurgical management strategies. PubMed database was searched for relevant articles in English on the issue of HCC management. Surgical resection represents a potentially curative option for appropriate candidates with tumors detected at earlier stages and with well-preserved liver function. The long-term outcome of surgery is impaired by a high rate of recurrence. Surgical approaches are being challenged by local ablative therapies such as radiofrequency ablation and microwave ablation in selected patients. Liver transplantation offers potential cure for HCC and also correction of underlying liver disease, and minimizes the risk of recurrence, but is reserved for patients within a set of criteria proposed for a prudent allocation in the shortage of donor organs. Transcatheter locoregional therapies have become the palliative standard allowing local control for intermediate stage patients with noninvasive multinodular or large HCC who are beyond the potentially curative options. The significant survival benefit with the multikinase inhibitor sorafenib for advanced HCC has shifted the direction of research regarding systemic treatment toward molecular therapies targeting the disregulated pathways of hepatocarcinogenesis. Potential benefit is suggested from simultaneous or sequential multimodal therapies, and optimal combinations are being investigated. Despite the striking progress in preclinical studies of HCC immunotherapy and gene therapy, extensive clinical trials are required to achieve successful clinical applications of these innovative approaches. Treatment decisions have become increasingly complex for HCC with the availability of multiple surgical and nonsurgical therapeutic options and require a comprehensive, multidisciplinary approach.

Edge and area effects on the occurrence of migrant forest songbirds

USGS Publications Warehouse

Parker, T.H.; Stansberry, B.M.; Becker, C.D.; Gipson, P.S.

2005-01-01

Concerns about forest fragmentation and its conservation implications have motivated numerous studies that investigate the influence of forest patch area and forest edge on songbird distribution patterns. The generalized effects of forest patch size and forest edge on animal distributions is still debatable because forest patch size and forest edge are often confounded and because of an incomplete synthesis of available data. To fill a portion of this gap, we incorporated all available published data (33 papers) in meta-analyses of forest edge and area effects on site occupancy patterns for 26 Neotropical migrant forest-nesting songbirds in eastern North America. All reported area effects are confounded or potentially confounded by edge effects, and we refer to these as "confounded" studies. The converse, however, is not true and most reported edge effects are independent of patch area. When considering only nonconfounded studies of edge effects, only 1 of 17 species showed significant edge avoidance and 3 had significant affinity for edges. In confounded studies, 12 of 22 species showed significant avoidance of small patches and edges, and 1 had an affinity for small patches and edges. Furthermore, average effect sizes averaged across studies or species tended to be higher for confounded studies than for edge studies. We discuss three possible reasons for differences in results between these two groups of studies. First, studies of edge effects tended to be carried out in landscapes with greater forest cover than studies of confounded effects; among confounded effects studies, as forest cover increased, we observed a nonsignificant trend towards decreasing strength of small patch or edge avoidance effects. Thus, the weaker effects in edge studies may be due to the fact that these studies were conducted in forest-dominated landscapes. Second, we may have detected strong effects only in confounded studies because area effects are much stronger than edge effects on bird occurrence, and area effects drive the results in confounded studies. Third, edge and area effects may interact in such a way that edge effects become more important as forest patch size decreases; thus, both edge and area effects are responsible for results in confounded studies. These three explanations cannot be adequately separated with existing data. Regardless, it is clear that fragmentation of forests into small patches is detrimental to many migrant songbird species. ??2005 Society for Conservation Biology.

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.

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

PubMed

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

2015-08-01

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

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

ERIC Educational Resources Information Center

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

2017-01-01

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

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

Rivers, runoff, and reefs

USGS Publications Warehouse

McLaughlin, C.J.; Smith, C.A.; Buddemeier, R.W.; Bartley, J.D.; Maxwell, B.A.

2003-01-01

The role of terrigenous sediment in controlling the occurrence of coral reef ecosystems is qualitatively understood and has been studied at local scales, but has not been systematically evaluated on a global-to-regional scale. Current concerns about degradation of reef environments and alteration of the hydrologic and sediment cycles place the issue at a focal point of multiple environmental concerns. We use a geospatial clustering of a coastal zone database of river and local runoff identified with 0.5?? grid cells to identify areas of high potential runoff effects, and combine this with a database of reported coral reef locations. Coastal cells with high runoff values are much less likely to contain reefs than low runoff cells and GIS buffer analysis demonstrates that this inhibition extends to offshore ocean cells as well. This analysis does not uniquely define the effects of sediment, since salinity, nutrients, and contaminants are potentially confounding variables also associated with runoff. However, sediment effects are likely to be a major factor and a basis is provided for extending the study to higher resolution with more specific variables. ?? 2003 Elsevier B.V. All rights reserved.

Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation.

PubMed

Cohen, Michael X; Gulbinaite, Rasa

2017-02-15

Steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency and time-frequency domains. The method, termed rhythmic entrainment source separation (RESS), is based on denoising source separation approaches that take advantage of the simultaneous but differential projection of neural activity to multiple electrodes or sensors. Our approach is a combination and extension of existing multivariate source separation methods. We demonstrate that RESS performs well on both simulated and empirical data, and outperforms conventional SSEP analysis methods based on selecting electrodes with the strongest SSEP response, as well as several other linear spatial filters. We also discuss the potential confound of overfitting, whereby the filter captures noise in absence of a signal. Matlab scripts are available to replicate and extend our simulations and methods. We conclude with some practical advice for optimizing SSEP data analyses and interpreting the results. Copyright © 2016 Elsevier Inc. All rights reserved.

Shame and guilt in the aftermath of terror: the Utøya Island study.

PubMed

Aakvaag, Helene Flood; Thoresen, Siri; Wentzel-Larsen, Tore; Røysamb, Espen; Dyb, Grete

2014-10-01

In recent years, there has been increased interest in trauma-related shame and guilt and their relationship to mental health. Little is known, however, about shame and guilt following mass traumas, such as terrorism. This study investigates the potential associations of trauma-related shame and guilt with posttraumatic stress (PTS) reactions after the terrorist attack of July 22, 2011 on Utøya Island in Norway. Interviews were conducted with 325 of the 490 survivors 4 to 5 months after the event. Multiple linear regression analyses were employed to investigate associations. In the month previous to the interview, 44.1% (n = 143) of participants had experienced at least some guilt for what happened during the attack, and 30.5% (n = 99) had experienced at least some shame. Shame and guilt were both uniquely associated with PTS reactions after adjusting for terror exposure, gender, and other potential confounders (frequent shame: B = 0.54, frequent guilt: B = 0.33). We concluded that trauma-related shame and guilt are related to mental health after mass trauma. Copyright © 2014 International Society for Traumatic Stress Studies.

Mood disorders: A potential link between ghrelin and leptin on human body?

PubMed

Zarouna, Stalo; Wozniak, Greta; Papachristou, Anastasia Ioannis

2015-05-20

Leptin and ghrelin are two hormones associated with multiple physiological functions, especially energy balance. Leptin is an adipocyte-secreted hormone discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone produced and secreted in the stomach. A number of previous studies showed that these hormones could be associated with different types of mood disorders. The results of previous studies, nevertheless, are confounded by diverse sample selection and different methodologies. A search for related articles in the PubMed database was attempted. The search covered studies, reports, reviews and editorials published in the last ten years. Older references served as auxiliary sources for comparison purposes. However, due to the different results of the studies, there is a need for more investigation in order to establish the exact biochemical mechanisms that are responsible for these diseases and ghrelin's and leptin's effects on mood.

[Homicide mortality, socioeconomic development, and police violence in the city of São Paulo, Brazil].

PubMed

Peres, Maria Fernanda Tourinho; Cardia, Nancy; de Mesquita Neto, Paulo; Dos Santos, Patrícia Carla; Adorno, Sérgio

2008-04-01

To analyze the association between police violence and homicide mortality rates taking into consideration the effect of contextual variables. This was an environmental, cross-sectional study that included the 96 census districts in the City of São Paulo. The association between the variables was analyzed using Spearman's rank correlation and simple and multiple regression analysis. Univariate analysis revealed a strong and significant association between homicide mortality coefficients and all the indicators of socioeconomic development and police violence. After controlling for potential confounding factors, the association between police violence and homicide mortality coefficients remained strong and significant. This significance was lost only after control for the size of the resident population. The results indicate that police action that violates basic human rights is not the right answer to urban violence. The combination of homicides from interpersonal violence and deaths from police violence results in negative socialization and promotes further violence.

Introduction to the use of regression models in epidemiology.

PubMed

Bender, Ralf

2009-01-01

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

Genomic perspectives on the birth and spread of plastids

PubMed Central

Archibald, John M.

2015-01-01

The endosymbiotic origin of plastids from cyanobacteria was a landmark event in the history of eukaryotic life. Subsequent to the evolution of primary plastids, photosynthesis spread from red and green algae to unrelated eukaryotes by secondary and tertiary endosymbiosis. Although the movement of cyanobacterial genes from endosymbiont to host is well studied, less is known about the migration of eukaryotic genes from one nucleus to the other in the context of serial endosymbiosis. Here I explore the magnitude and potential impact of nucleus-to-nucleus endosymbiotic gene transfer in the evolution of complex algae, and the extent to which such transfers compromise our ability to infer the deep structure of the eukaryotic tree of life. In addition to endosymbiotic gene transfer, horizontal gene transfer events occurring before, during, and after endosymbioses further confound our efforts to reconstruct the ancient mergers that forged multiple lines of photosynthetic microbial eukaryotes. PMID:25902528

Health-Related Quality of Life Among US Workers: Variability Across Occupation Groups.

PubMed

Shockey, Taylor M; Zack, Matthew; Sussell, Aaron

2017-08-01

To examine the health-related quality of life among workers in 22 standard occupation groups using data from the 2013-2014 US Behavioral Risk Factor Surveillance System. We examined the health-related quality of life measures of self-rated health, frequent physical distress, frequent mental distress, frequent activity limitation, and frequent overall unhealthy days by occupation group for 155 839 currently employed adults among 17 states. We performed multiple logistic regression analyses that accounted for the Behavioral Risk Factor Surveillance System's complex survey design to obtain prevalence estimates adjusted for potential confounders. Among all occupation groups, the arts, design, entertainment, sports, and media occupation group reported the highest adjusted prevalence of frequent physical distress, frequent mental distress, frequent activity limitation, and frequent overall unhealthy days. The personal care and service occupation group had the highest adjusted prevalence for fair or poor self-rated health. Workers' jobs affect their health-related quality of life.

Genomic perspectives on the birth and spread of plastids.

PubMed

Archibald, John M

2015-08-18

The endosymbiotic origin of plastids from cyanobacteria was a landmark event in the history of eukaryotic life. Subsequent to the evolution of primary plastids, photosynthesis spread from red and green algae to unrelated eukaryotes by secondary and tertiary endosymbiosis. Although the movement of cyanobacterial genes from endosymbiont to host is well studied, less is known about the migration of eukaryotic genes from one nucleus to the other in the context of serial endosymbiosis. Here I explore the magnitude and potential impact of nucleus-to-nucleus endosymbiotic gene transfer in the evolution of complex algae, and the extent to which such transfers compromise our ability to infer the deep structure of the eukaryotic tree of life. In addition to endosymbiotic gene transfer, horizontal gene transfer events occurring before, during, and after endosymbioses further confound our efforts to reconstruct the ancient mergers that forged multiple lines of photosynthetic microbial eukaryotes.

Familial risk moderates the association between sleep and zBMI in children.

PubMed

Bagley, Erika J; El-Sheikh, Mona

2013-08-01

A cumulative risk approach was used to examine the moderating effect of familial risk factors on relations between actigraphy-based sleep quantity (minutes) and quality (efficiency) and sex- and age-standardized body mass index (zBMI). The sample included 124 boys and 104 girls with a mean age of 10.41 years (SD = 0.67). Children wore actigraphs for 1 week, and their height and weight were assessed in the lab. After controlling for potential confounds, multiple regression analyses indicated that sleep minutes predicted children's zBMI and that both sleep minutes and efficiency interacted with family risk in the prediction of zBMI. The association between poor sleep and zBMI was especially evident for children exposed to higher levels of family risk. Findings suggest that not all children who exhibit poor sleep are at equal risk for higher zBMI and that familial and contextual conditions need to be considered in this link.

Effects of biometrics, location and persistent organic pollutants on blood clinical-chemical parameters in polar bears (Ursus maritimus) from Svalbard, Norway.

PubMed

Ciesielski, Tomasz Maciej; Sonne, Christian; Ormbostad, Ingunn; Aars, Jon; Lie, Elisabeth; Bytingsvik, Jenny; Jenssen, Bjørn Munro

2018-05-31

In the present study, blood clinical-chemical parameters (BCCPs) were analysed in 20 female and 18 male Svalbard polar bears (Ursus maritimus) captured in spring 2007. The aim was to study how age, body condition (BC), biometrics, plasma lipid content and geographical location may confound the relationship between persistent organic pollutants (POPs) including PCBs, HCB, chlordanes, DDTs, HCHs, mirex and OH-PCBs and the concentrations of 12 specific BCCPs (hematocrit [HCT], hemoglobin [HB], aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], γ-glutamyltransferase [GGT], creatine kinase [CK], triglycerides [TG], cholesterol [CHOL], high-density lipoprotein [HDL], creatinine (CREA], urea, potassium (K]), and to investigate if any of these BCCPs may be applied as potential biomarkers for POP exposure in polar bears. Initial PCA and O-PLS modelling showed that age, lipids, BC and geographical location (longitude and latitude) were important parameters explaining BCCPs in females. Following subsequent partial correlation analyses correcting for age and lipids, multiple POPs in females were still significantly correlated with HCT and HDL (all p < 0.05). In males, age, BM, BC and longitude were important parameters explaining BCCPs. Following partial correlation analyses correcting for age, biometrics, lipids and longitude in males, multiple POPs were significantly correlated with HCT, ASAT, GGT and CHOL (all p < 0.05). In conclusion, several confounding parameters has to be taken into account when studying the relations between BCCPs and POPs in polar bears. When correcting for these, in particular HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. Furthermore, decreasing HDL concentrations and increasing CHOL concentration with increasing POP concentrations may indicate responses related to increased risk of cardiovascular disease. We therefore suggest to further study POP exposure and lipidome response to increase knowledge of the risk of cardiometabolic syndrome in polar bears. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of total marine fatty acids, eicosapentaenoic and docosahexaenoic acids, with aortic stiffness in Koreans, whites, and Japanese Americans.

PubMed

Sekikawa, Akira; Shin, Chol; Masaki, Kamal H; Barinas-Mitchell, Emma J M; Hirooka, Nobutaka; Willcox, Bradley J; Choo, Jina; White, Jessica; Evans, Rhobert W; Fujiyoshi, Akira; Okamura, Tomonori; Miura, Katsuyuki; Muldoon, Matthew F; Ueshima, Hirotsugu; Kuller, Lewis H; Sutton-Tyrrell, Kim

2013-11-01

Few previous studies have reported the association of aortic stiffness with marine n-3 fatty acids (Fas) in the general population. The aim of this study was to determine the combined and independent associations of 2 major marine n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with aortic stiffness evaluated using carotid-femoral pulse wave velocity (cfPWV) in Korean, white, and Japanese American men. A population-based sample of 851 middle-aged men (299 Koreans, 266 whites, and 286 Japanese Americans) was examined for cfPWV during 2002-2006. Serum FAs, including EPA and DHA, were measured as a percentage of total FAs using gas chromatography. Multiple regression analysis was used to examine the association of EPA and DHA with cfPWV after adjusting for blood pressure and other confounders. Mean EPA and DHA levels were 1.9 (SD = 1.0) and 4.8 (SD = 1.4) for Koreans, 0.8 (SD = 0.6) and 2.4 (SD = 1.2) for whites, and 1.0 (SD = 1.0) and 3.2 (SD = 1.4) for Japanese Americans. Both EPA and DHA were significantly higher in Koreans than in the other 2 groups (P < 0.01). Multiple regression analyses in Koreans showed that cfPWV had a significant inverse association with total marine n-3 FAs and with EPA alone after adjusting for blood pressure and other potential confounders. In contrast, there was no significant association of cfPWV with DHA. Whites and Japanese Americans did not show any significant associations of cfPWV with total marine n-3 FAs, EPA, or DHA. High levels of EPA observed in Koreans have an inverse association with aortic stiffness. © American Journal of Hypertension, Ltd 2013. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gender-related mental health differences between refugees and non-refugee immigrants - a cross-sectional register-based study

PubMed Central

2011-01-01

Background Being an immigrant in a high-income country is a risk factor for severe mental ill health. Studies on mental ill health among immigrants have found significant differences in mental health outcome between immigrants from high income countries and low-income countries. Being an asylum seeker or a refugee is also associated with mental ill health. This study aimed to assess if there is a difference in mental ill health problems between male and female refugee and non-refugee immigrants from six low-income countries in Sweden. Methods A cross-sectional, population-based study design was used comparing refugees with non-refugees. The study size was determined by the number of persons in Sweden fulfilling the inclusion criteria at the time of the study during 2006. Outcome: Mental ill health, as measured with the proxy variable psychotropic drugs purchased. Refugee/Non-refugee: Sweden grants asylum to refugees according to the Geneva Convention and those with a well-grounded fear of death penalty, torture or who need protection due to an internal or external armed conflict or an environmental disaster. The non-refugees were all family members of those granted asylum in Sweden. Covariates: Gender and origin. Potential confounders: Age, marital status, education and duration of stay in Sweden. Background variables were analysed using chi square tests. The association between outcome, exposure and possible confounders was analysed using logistic regression analyses. Multiple logistic regression analysis was used to adjust for potential confounders. Results The study population comprised 43,168 refugees and non-refugees, of whom 20,940 (48.5%) were women and 24,403 (56.5%) were refugees. Gender, age, origin, marital status and education were all associated with the outcome. For female, but not male, refugees there was a significantly higher likelihood of purchasing psychotropic drugs than non-refugees (OR = 1.27, 95% CI = 1.15 - 1.40). Conclusions Female refugees from low-income countries seem to be a risk group among immigrant women from low-income countries, whereas male refugees had the same risk patterns as non-refugee immigrants from low-income countries. This underlines the need for training of clinicians in order to focus on pre-migration stress and the asylum process, among female newcomers. PMID:21435212

Gender-related mental health differences between refugees and non-refugee immigrants--a cross-sectional register-based study.

PubMed

Hollander, Anna-Clara; Bruce, Daniel; Burström, Bo; Ekblad, Solvig

2011-03-24

Being an immigrant in a high-income country is a risk factor for severe mental ill health. Studies on mental ill health among immigrants have found significant differences in mental health outcome between immigrants from high income countries and low-income countries. Being an asylum seeker or a refugee is also associated with mental ill health. This study aimed to assess if there is a difference in mental ill health problems between male and female refugee and non-refugee immigrants from six low-income countries in Sweden. A cross-sectional, population-based study design was used comparing refugees with non-refugees. The study size was determined by the number of persons in Sweden fulfilling the inclusion criteria at the time of the study during 2006. Mental ill health, as measured with the proxy variable psychotropic drugs purchased. Refugee/Non-refugee: Sweden grants asylum to refugees according to the Geneva Convention and those with a well-grounded fear of death penalty, torture or who need protection due to an internal or external armed conflict or an environmental disaster. The non-refugees were all family members of those granted asylum in Sweden. Covariates: Gender and origin. Potential confounders: Age, marital status, education and duration of stay in Sweden. Background variables were analysed using chi square tests. The association between outcome, exposure and possible confounders was analysed using logistic regression analyses. Multiple logistic regression analysis was used to adjust for potential confounders. The study population comprised 43,168 refugees and non-refugees, of whom 20,940 (48.5%) were women and 24,403 (56.5%) were refugees. Gender, age, origin, marital status and education were all associated with the outcome. For female, but not male, refugees there was a significantly higher likelihood of purchasing psychotropic drugs than non-refugees (OR = 1.27, 95% CI = 1.15-1.40). Female refugees from low-income countries seem to be a risk group among immigrant women from low-income countries, whereas male refugees had the same risk patterns as non-refugee immigrants from low-income countries. This underlines the need for training of clinicians in order to focus on pre-migration stress and the asylum process, among female newcomers.

Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies

PubMed Central

Liu, Xiaolei; Huang, Meng; Fan, Bin; Buckler, Edward S.; Zhang, Zhiwu

2016-01-01

False positives in a Genome-Wide Association Study (GWAS) can be effectively controlled by a fixed effect and random effect Mixed Linear Model (MLM) that incorporates population structure and kinship among individuals to adjust association tests on markers; however, the adjustment also compromises true positives. The modified MLM method, Multiple Loci Linear Mixed Model (MLMM), incorporates multiple markers simultaneously as covariates in a stepwise MLM to partially remove the confounding between testing markers and kinship. To completely eliminate the confounding, we divided MLMM into two parts: Fixed Effect Model (FEM) and a Random Effect Model (REM) and use them iteratively. FEM contains testing markers, one at a time, and multiple associated markers as covariates to control false positives. To avoid model over-fitting problem in FEM, the associated markers are estimated in REM by using them to define kinship. The P values of testing markers and the associated markers are unified at each iteration. We named the new method as Fixed and random model Circulating Probability Unification (FarmCPU). Both real and simulated data analyses demonstrated that FarmCPU improves statistical power compared to current methods. Additional benefits include an efficient computing time that is linear to both number of individuals and number of markers. Now, a dataset with half million individuals and half million markers can be analyzed within three days. PMID:26828793

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.

Multiple sclerosis in pregnancy: prevalence, sociodemographic features, and obstetrical outcomes.

PubMed

Fong, Alex; Chau, Cindy T; Quant, Cara; Duffy, Jennifer; Pan, Deyu; Ogunyemi, Dotun A

2018-02-01

We sought to describe the prevalence, sociodemographic features, and antenatal/peripartum outcomes of multiple sclerosis (MS) in pregnancy. A retrospective cohort study was performed using deliveries in California from 2001 to 2009. Cases of MS as well as other morbidities were identified via ICD-9-CM code. Logistic regression was performed to adjust for potential confounders. About 1185 out of 4,424,049 deliveries were complicated by MS. MS prevalence increased with maternal age, with Caucasians comprising a higher proportion of MS subjects. MS subjects were older and more likely to have private insurance. Women with MS were more likely to have preexisting medical conditions such as asthma, chronic hypertension, thyroid disease, or cardiac disease. However, no significant antepartum and peripartum morbidities were found to be increased in patients with MS. Urinary tract infection, cesarean delivery, and induction of labor were slightly increased in MS patients. MS is a rare condition which is more likely to affect older Caucasian women of higher socioeconomic status and is associated with several preexisting medical conditions. MS, however, does not appear to pose significant increases in adverse pregnancy outcome. This suggests that pregnant patients with MS may likely experience an uneventful pregnancy.

Parent figure transitions and delinquency and drug use among early adolescent children of substance abusers.

PubMed

Keller, Thomas E; Catalano, Richard F; Haggerty, Kevin P; Fleming, Charles B

2002-01-01

Children of substance abusing parents have an elevated risk for experiencing disruptions in household composition and for engaging in problem behaviors. This study investigated whether multiple parent figure transitions predicted the likelihood of delinquency and drug use among a sample of early adolescents with parents receiving methadone treatment for opiate addiction. Controlling for baseline delinquency, child characteristics, family conflict, parental depression, and parent criminal history, a greater number of parenting disruptions during the longitudinal study period was associated with a higher probability of delinquent behavior. Gender moderated the effect of parent figure transitions in a parallel analysis for drug use. After accounting for baseline drug use and potentially confounding factors, only adolescent females had a higher likelihood of drug use as the number of family disruptions increased. In contrast, age was strongly associated with drug use for males. A subgroup of youths who experienced tremendous family instability and had no single consistent parent figure during the study period were at extreme risk for delinquent behavior. The findings are interpreted in terms of cumulative stress resulting from multiple parenting disruptions over time and differential influences on the expression of problem behaviors depending on gender.

Information processing efficiency in patients with multiple sclerosis.

PubMed

Archibald, C J; Fisk, J D

2000-10-01

Reduced information processing efficiency, consequent to impaired neural transmission, has been proposed as underlying various cognitive problems in patients with Multiple Sclerosis (MS). This study employed two measures developed from experimental psychology that control for the potential confound of perceptual-motor abnormalities (Salthouse, Babcock, & Shaw, 1991; Sternberg, 1966, 1969) to assess the speed of information processing and working memory capacity in patients with mild to moderate MS. Although patients had significantly more cognitive complaints than neurologically intact matched controls, their performance on standard tests of immediate memory span did not differ from control participants and their word list learning was within normal limits. On the experimental measures, both relapsing-remitting and secondary-progressive patients exhibited significantly slowed information processing speed relative to controls. However, only the secondary-progressive patients had an additional decrement in working memory capacity. Depression, fatigue, or neurologic disability did not account for performance differences on these measures. While speed of information processing may be slowed early in the disease process, deficits in working memory capacity may appear only as there is progression of MS. It is these latter deficits, however, that may underlie the impairment of new learning that patients with MS demonstrate.

Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems.

PubMed

Narazaki, Kenji; Matsuo, Eri; Honda, Takanori; Nofuji, Yu; Yonemoto, Koji; Kumagai, Shuzo

2014-09-01

Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24) were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%). Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p < 0.001). These associations were preserved after additional adjustment for years of formal education, body mass index, and other confounding factors (p < 0.001). The present study first demonstrated the associations between multiple aspects of physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community-based preventive care of dementia. Key pointsThere is a great need for identifying lifestyle-related markers which help detect subtle cognitive impairment in the preclinical or earlier phase of dementia.In the present study, each of the five physical fitness measures employed was linearly and positively associated with the Montreal Cognitive Assessment score in the present older adults without apparent cognitive problems, after adjusting for age, sex, education, body mass index, and other confounding factors.The results suggest the potential of each physical fitness measure as a single lifestyle-related marker of low cognitive function in the population, which can be useful in community-based preventive care of dementia.

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.

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

PubMed

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

2008-04-30

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

Dioxin-like compounds are not associated with bone strength measured by ultrasonography in Inuit women from Nunavik (Canada): results of a cross-sectional study.

PubMed

Paunescu, Alexandra-Cristina; Ayotte, Pierre; Dewailly, Eric; Dodin, Sylvie

2013-01-01

Bone strength in Inuit people appears lower than that of non-Aboriginals. Inuit are exposed to persistent organic pollutants including dioxin-like compounds (DLCs) through their traditional diet that comprises predatory fish and marine mammal fat. Results from experimental and population studies suggest that some DLCs can alter bone metabolism and increase bone fragility. This cross-sectional descriptive study was conducted to examine the relationship between the stiffness index (SI) and plasma concentrations of total DLCs or specific dioxin-like polychlorinated biphenyls (DL-PCBs) in Inuit women of Nunavik (Northern Quebec, Canada). SI was determined by ultrasonography at the right calcaneus of 194 Inuit women aged 35-72 years who participated to Qanuippitaa? How Are We? Nunavik Inuit Health Survey in 2004. Plasma total DLC levels were quantified by measuring the aryl hydrocarbon receptor-mediated transcriptional activity elicited by plasma sample extracts in a cell-based reporter gene assay. Plasma concentrations of DL-PCBs nos. 105, 118, 156, 157, 167 and 189 were measured by gas chromatography-mass spectrometry. We used multiple linear regression analyses to investigate relations between total DLCs or specific DL-PCBs and SI, taking into consideration several potential confounders. Neither total plasma DLCs nor specific DL-PCBs were associated with SI after adjustment for several confounders and covariates. Our results do not support a relation between exposure to DLCs and bone strength measured by ultrasonography in Inuit women of Nunavik.

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.

A Comparison of Agent-Based Models and the Parametric G-Formula for Causal Inference.

PubMed

Murray, Eleanor J; Robins, James M; Seage, George R; Freedberg, Kenneth A; Hernán, Miguel A

2017-07-15

Decision-making requires choosing from treatments on the basis of correctly estimated outcome distributions under each treatment. In the absence of randomized trials, 2 possible approaches are the parametric g-formula and agent-based models (ABMs). The g-formula has been used exclusively to estimate effects in the population from which data were collected, whereas ABMs are commonly used to estimate effects in multiple populations, necessitating stronger assumptions. Here, we describe potential biases that arise when ABM assumptions do not hold. To do so, we estimated 12-month mortality risk in simulated populations differing in prevalence of an unknown common cause of mortality and a time-varying confounder. The ABM and g-formula correctly estimated mortality and causal effects when all inputs were from the target population. However, whenever any inputs came from another population, the ABM gave biased estimates of mortality-and often of causal effects even when the true effect was null. In the absence of unmeasured confounding and model misspecification, both methods produce valid causal inferences for a given population when all inputs are from that population. However, ABMs may result in bias when extrapolated to populations that differ on the distribution of unmeasured outcome determinants, even when the causal network linking variables is identical. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association between zolpidem use and glaucoma risk: a Taiwanese population-based case-control study.

PubMed

Ho, Yi-Hao; Chang, Yue-Cune; Huang, Wei-Cheng; Chen, Hsin-Yi; Lin, Che-Chen; Sung, Fung-Chang

2015-01-01

To date, the relationship between zolpidem use and subsequent risk of glaucoma in a Taiwanese population has not been assessed. We used data from the National Health Insurance system to investigate whether zolpidem use was related to glaucoma risk. A 1:4 matched case-control study was conducted. The cases were patients newly diagnosed with glaucoma from 2001 to 2010. The controls were randomly selected non-glaucoma subjects matched by sex and age (± 5 years). Zolpidem exposure and/or the average dosage of zolpidem used (mg/year) were evaluated. Medical comorbidities were considered as confounding factors. Multiple logistic regression models were used to evaluate the potential risk of zolpidem exposure on glaucoma with/without adjustment for the effects of confounding variables. The exposure rate of zolpidem use in the glaucoma group was significantly higher than that of the control group (2.8% vs. 2.0%, P < 0.0001). The adjusted odds ratio (OR) of the risk of glaucoma for those with zolpidem use vs. those without was 1.19 (95% confidence interval [CI], 1.02-1.38). Compared to non-zolpidem users, zolpidem users with an average dose of more than 200 mg/year had significantly increased risk of glaucoma (OR 1.31, 95% CI 1.03-1.68). This study suggests that the use of zolpidem might increase the risk of subsequent glaucoma. Further confirmatory studies are recommended to clarify this important issue.

Association Between Zolpidem Use and Glaucoma Risk: A Taiwanese Population-Based Case-Control Study

PubMed Central

Ho, Yi-Hao; Chang, Yue-Cune; Huang, Wei-Cheng; Chen, Hsin-Yi; Lin, Che-Chen; Sung, Fung-Chang

2015-01-01

Background To date, the relationship between zolpidem use and subsequent risk of glaucoma in a Taiwanese population has not been assessed. Methods We used data from the National Health Insurance system to investigate whether zolpidem use was related to glaucoma risk. A 1:4 matched case-control study was conducted. The cases were patients newly diagnosed with glaucoma from 2001 to 2010. The controls were randomly selected non-glaucoma subjects matched by sex and age (±5 years). Zolpidem exposure and/or the average dosage of zolpidem used (mg/year) were evaluated. Medical comorbidities were considered as confounding factors. Multiple logistic regression models were used to evaluate the potential risk of zolpidem exposure on glaucoma with/without adjustment for the effects of confounding variables. Results The exposure rate of zolpidem use in the glaucoma group was significantly higher than that of the control group (2.8% vs. 2.0%, P < 0.0001). The adjusted odds ratio (OR) of the risk of glaucoma for those with zolpidem use vs. those without was 1.19 (95% confidence interval [CI], 1.02–1.38). Compared to non-zolpidem users, zolpidem users with an average dose of more than 200 mg/year had significantly increased risk of glaucoma (OR 1.31, 95% CI 1.03–1.68). Conclusions This study suggests that the use of zolpidem might increase the risk of subsequent glaucoma. Further confirmatory studies are recommended to clarify this important issue. PMID:25720944

Association Between Zolpidem Use and Glaucoma Risk: A Taiwanese Population-Based Case-Control Study.

PubMed

Ho, Yi-Hao; Chang, Yue-Cune; Huang, Wei-Cheng; Chen, Hsin-Yi; Lin, Che-Chen; Sung, Fung-Chang

2014-08-23

Background: To date, the relationship between zolpidem use and subsequent risk of glaucoma in a Taiwanese population has not been assessed.Methods: We used data from the National Health Insurance system to investigate whether zolpidem use was related to glaucoma risk. A 1:4 matched case-control study was conducted. The cases were patients newly diagnosed with glaucoma from 2001 to 2010. The controls were randomly selected non-glaucoma subjects matched by sex and age (±5 years). Zolpidem exposure and/or the average dosage of zolpidem used (mg/year) were evaluated. Medical comorbidities were considered as confounding factors. Multiple logistic regression models were used to evaluate the potential risk of zolpidem exposure on glaucoma with/without adjustment for the effects of confounding variables.Results: The exposure rate of zolpidem use in the glaucoma group was significantly higher than that of the control group (2.8% vs. 2.0%, P < 0.0001). The adjusted odds ratio (OR) of the risk of glaucoma for those with zolpidem use vs. those without was 1.19 (95% confidence interval [CI], 1.02-1.38). Compared to non-zolpidem users, zolpidem users with an average dose of more than 200 mg/year had significantly increased risk of glaucoma (OR 1.31, 95% CI 1.03-1.68).Conclusions: This study suggests that the use of zolpidem might increase the risk of subsequent glaucoma. Further confirmatory studies are recommended to clarify this important issue.

Does substantiated childhood maltreatment lead to poor quality of life in young adulthood? Evidence from an Australian birth cohort study.

PubMed

Abajobir, Amanuel Alemu; Kisely, Steve; Williams, Gail; Strathearn, Lane; Clavarino, Alexandra; Najman, Jake Moses

2017-07-01

To examine the independent effect of single and multiple forms of substantiated childhood maltreatment (CM) on quality of life (QoL), controlling for selected potential confounders and/or covariates, and concurrent depressive symptoms. We used data from a prospective pre-birth cohort of 8556 mothers recruited consecutively during their first antenatal clinic visit at the Mater Hospital from 1981 to 1983 in Brisbane, Australia. The data were linked to substantiated cases of CM reported to the child protection government agency up to the age of 14 years. The sample consisted of 3730 (49.7% female) young adults for whom there were complete data on QoL at the 21-year follow-up. The mean age of participants was 20.6 years. Logistic regression models were used to assess the association between CM and QoL measured at the 21-year follow-up. There were statistically significant associations between exposure to substantiated CM and poorer QoL. This also applied to the subcategories of childhood physical abuse, childhood emotional abuse (CEA), and neglect. These associations were generally stable after adjusting for confounders/covariates and concurrent depressive symptoms, except physical abuse. CEA with or without neglect significantly and particularly predicted worse subsequent QoL. Exposure to any substantiated maltreatment substantially contributed to worse QoL in young adulthood, with a particular association with CEA and neglect. Prior experiences of CM may have a substantial association with subsequent poorer QoL.

Rapid neck muscle adaptation alters the head kinematics of aware and unaware subjects undergoing multiple whiplash-like perturbations.

PubMed

Siegmund, Gunter P; Sanderson, David J; Myers, Barry S; Inglis, J Timothy

2003-04-01

To examine whether habituation confounds the study of whiplash injury using human subjects, we quantified changes in the magnitude and temporal development of the neck muscle electromyogram and peak linear and angular head/torso kinematics of subjects exposed to sequential whiplash-like perturbations. Forty-four seated subjects (23F, 21M) underwent 11 consecutive forward horizontal perturbations (peak sled acceleration=1.5 g). Electromyographic (EMG) activity was recorded over the sternocleidomastoid (SCM) and cervical paraspinal (PARA) muscles with surface electrodes, and head and torso kinematics were measured using linear and angular accelerometers and a 3D motion analysis system. EMG onset occurred at reflex latencies (67-75 ms in SCM) and did not vary with repeated perturbations. EMG amplitude was significantly attenuated by the second perturbation in PARA muscles and by the third perturbation in SCM muscles. The mean decrement in EMG amplitude between the first trial and the mean of the last five trials was between 41% and 64%. Related kinematic changes ranged from a 21% increase in head extension angle to a 29% decrease in forward acceleration at the forehead, and were also significantly different by the second exposure in some variables. Although a wider range of perturbation intensities and inter-perturbation intervals need to be studied, the significant changes observed in both muscle and kinematic variables by the second perturbation indicated that habituation was a potential confounder of whiplash injury studies using repeated perturbations of human subjects.

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 ...

Ten years of helicopter emergency medical services in Germany: do we still need the helicopter rescue in multiple traumatised patients?

PubMed

Andruszkow, Hagen; Hildebrand, Frank; Lefering, Rolf; Pape, Hans-Christoph; Hoffmann, Reinhard; Schweigkofler, Uwe

2014-10-01

Helicopter emergency medical service (HEMS) has been established in the preclinical treatment of multiple traumatised patients despite an ongoing controversy towards the potential benefit. Celebrating the 20th anniversary of TraumaRegister DGU(®) of the German Trauma Society (DGU) the presented study intended to provide an overview of HEMS rescue in Germany over the last 10 years analysing the potential beneficial impact of a nationwide helicopter rescue in multiple traumatised patients. We analysed TraumaRegister DGU(®) including multiple traumatised patients (ISS ≥ 16) between 2002 and 2012. In-hospital mortality was defined as main outcome. An adjusted, multivariate regression with 13 confounders was performed to evaluate the potential survival benefit. 42,788 patients were included in the present study. 14,275 (33.4%) patients were rescued by HEMS and 28,513 (66.6%) by GEMS. Overall, 66.8% (n=28,569) patients were transported to a level I trauma centre and 28.2% (n=12,052) to a level II trauma centre. Patients rescued by HEMS sustained a higher injury severity compared to GEMS (ISS HEMS: 29.5 ± 12.6 vs. 27.5 ± 11.8). Helicopter rescue teams performed more on-scene interventions, and mission times were increased in HEMS rescue (HEMS: 77.2 ± 28.7 min. vs. GEMS: 60.9 ± 26.9 min.). Linear regression analysis revealed that the frequency of HEMS rescue has decreased significantly between 2002 and 2012. In case of transportation to level I trauma centres a decrease of 1.7% per year was noted (p<0.001) while a decline of 1.6% per year (p<0.001) was measured for level II trauma centre admissions. According to multivariate logistic regression HEMS was proven a positive independent survival predictor between 2002 and 2012 (OR 0.863; 95%-CI 0.800-0.930; Nagelkerkes-R(2) 0.539) with only little differences between each year. This study was able to prove an independent survival benefit of HEMS in multiple traumatised patients during the last 10 years. Despite this fact, a constant decline of HEMS rescue missions was found in multiple trauma patients due to unknown reasons. We concluded that HEMS should be used more often in case of trauma in order to guarantee the proven benefit for multiple traumatised patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Embedded Diagnostic/Prognostic Reasoning and Information Continuity for Improved Avionics Maintenance

DTIC Science & Technology

2006-01-01

enabling technologies such as built-in-test, advanced health monitoring algorithms, reliability and component aging models, prognostics methods, and...deployment and acceptance. This framework and vision is consistent with the onboard PHM ( Prognostic and Health Management) as well as advanced... monitored . In addition to the prognostic forecasting capabilities provided by monitoring system power, multiple confounding errors by electronic

Unidimensional IRT Item Parameter Estimates across Equivalent Test Forms with Confounding Specifications within Dimensions

ERIC Educational Resources Information Center

Matlock, Ki Lynn; Turner, Ronna

2016-01-01

When constructing multiple test forms, the number of items and the total test difficulty are often equivalent. Not all test developers match the number of items and/or average item difficulty within subcontent areas. In this simulation study, six test forms were constructed having an equal number of items and average item difficulty overall.…

[Effect of social desirability on dietary intake estimated from a food questionnaire].

PubMed

Barros, Renata; Moreira, Pedro; Oliveira, Bruno

2005-01-01

Self-report of dietary intake could be biased by social thus affecting risk estimates in epidemiological studies. The objective of study was to assess the effect of social desirability on dietary intake from a food frequency questionnaire (FFQ). A convenience sample of 483 Portuguese university students was recruited. Subjects were invited to complete a two-part self-administered questionnaire: the first part included the Marlowe-Crowne Social Desirability Scale (M-CSDS), a physical activity questionnaire and self-reported height and weight; the second part, included a semi-quantitative FFQ validated for Portuguese adults, that should be returned after fulfillment. All subjects completed the first part of the questionnaire and 40.4% returned the FFQ fairly completed. In multiple regression analysis, after adjustment for energy and confounders, social desirability produced a significant positive effect in the estimates of dietary fibre, vitamin C, vitamin E, magnesium and potassium, in both genders. In multiple regression, after adjustment for energy and confounders, social desirability had a significant positive effect in the estimates of vegetable consumption, for both genders, and a negative effect in white bread and beer, for women. Social desirability affected nutritional and food intake estimated from a food frequency questionnaire.

Assessment of imperfect detection of blister rust in whitebark pine within the Greater Yellowstone Ecosystem

USGS Publications Warehouse

Wright, Wilson J.; Irvine, Kathryn M.

2017-01-01

We examined data on white pine blister rust (blister rust) collected during the monitoring of whitebark pine trees in the Greater Yellowstone Ecosystem (from 2004-2015). Summaries of repeat observations performed by multiple independent observers are reviewed and discussed. These summaries show variability among observers and the potential for errors being made in blister rust status. Based on this assessment, we utilized occupancy models to analyze blister rust prevalence while explicitly accounting for imperfect detection. Available covariates were used to model both the probability of a tree being infected with blister rust and the probability of an observer detecting the infection. The fitted model provided strong evidence that the probability of blister rust infection increases as tree diameter increases and decreases as site elevation increases. Most importantly, we found evidence of heterogeneity in detection probabilities related to tree size and average slope of a transect. These results suggested that detecting the presence of blister rust was more difficult in larger trees. Also, there was evidence that blister rust was easier to detect on transects located on steeper slopes. Our model accounted for potential impacts of observer experience on blister rust detection probabilities and also showed moderate variability among the different observers in their ability to detect blister rust. Based on these model results, we suggest that multiple observer sampling continue in future field seasons in order to allow blister rust prevalence estimates to be corrected for imperfect detection. We suggest that the multiple observer effort be spread out across many transects (instead of concentrated at a few each field season) while retaining the overall proportion of trees with multiple observers around 5-20%. Estimates of prevalence are confounded with detection unless it is explicitly accounted for in an analysis and we demonstrate how an occupancy model can be used to do account for this source of observation error.

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

PubMed

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

2004-07-01

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

Real-Time Assessment of Fatigue in Patients With Multiple Sclerosis: How Does It Relate to Commonly Used Self-Report Fatigue Questionnaires?

PubMed

Heine, Martin; van den Akker, Lizanne Eva; Blikman, Lyan; Hoekstra, Trynke; van Munster, Erik; Verschuren, Olaf; Visser-Meily, Anne; Kwakkel, Gert

2016-11-01

(1) To assess real-time patterns of fatigue; (2) to assess the association between a real-time fatigue score and 3 commonly used questionnaires (Checklist Individual Strength [CIS] fatigue subscale, Modified Fatigue Impact Scale (MFIS), and Fatigue Severity Scale [FSS]); and (3) to establish factors that confound the association between the real-time fatigue score and the conventional fatigue questionnaires in patients with multiple sclerosis (MS). Cross-sectional study. MS-specialized outpatient facility. Ambulant patients with MS (N=165) experiencing severe self-reported fatigue. Not applicable. A real-time fatigue score was assessed by sending participants 4 text messages on a particular day (How fatigued do you feel at this moment?; score range, 0-10). Latent class growth mixed modeling was used to determine diurnal patterns of fatigue. Regression analyses were used to assess the association between the mean real-time fatigue score and the CIS fatigue subscale, MFIS, and FSS. Significant associations were tested for candidate confounders (eg, disease severity, work status, sleepiness). Four significantly different fatigue profiles were identified by the real-time fatigue score, namely a stable high (n=79), increasing (n=57), stable low (n=16), and decreasing (n=13). The conventional questionnaires correlated poorly (r<.300) with the real-time fatigue score. The Epworth Sleepiness Scale significantly reduced the regression coefficient between the real-time fatigue score and conventional questionnaires, ranging from 15.4% to 35%. Perceived fatigue showed 4 different diurnal patterns in patients with MS. Severity of sleepiness is an important confounder to take into account in the assessment of fatigue. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Bark analysis as a guide to cassava nutrition in Sierra Leone

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

Godfrey-Sam-Aggrey, W.; Garber, M.J.

1979-01-01

Cassava main stem barks from two experiments in which similar fertilizers were applied directly in a 2/sup 5/ confounded factorial design were analyzed and the bark nutrients used as a guide to cassava nutrition. The application of multiple regression analysis to the respective root yields and bark nutrient concentrations enable nutrient levels and optimum adjusted root yields to be derived. Differences in bark nutrient concentrations reflected soil fertility levels. Bark analysis and the application of multiple regression analysis to root yields and bark nutrients appear to be useful tools for predicting fertilizer recommendations for cassava production.

Pre- and Perinatal Risk for Attention-Deficit Hyperactivity Disorder: Does Neuropsychological Weakness Explain the Link?

PubMed

Wiggs, Kelsey; Elmore, Alexis L; Nigg, Joel T; Nikolas, Molly A

2016-11-01

Etiological investigations of attention-deficit hyperactivity disorder (ADHD) and disruptive behavior problems support multiple causal pathways, including involvement of pre- and perinatal risk factors. Because these risks occur early in life, well before observable ADHD and externalizing symptoms emerge, the relation between risk and symptoms may be mediated by neurodevelopmental effects that manifest later in neuropsychological functioning. However, potential dissociable effects of pre/perinatal risk elements on ADHD and familial confounds must also be considered to test alternative hypotheses. 498 youth aged 6-17 years (55.0 % male) completed a multi-stage, multi-informant assessment including parent and teacher symptom reports of symptoms and parent ratings of pre/perinatal health risk indicators. Youth completed a neuropsychological testing battery. Multiple mediation models examined direct effects of pre- and perinatal health risk on ADHD and other disruptive behavior disorder symptoms and indirect effects via neuropsychological functioning. Parental ADHD symptoms and externalizing status was covaried to control for potential familial effects. Effects of prenatal substance exposure on inattention were mediated by memory span and temporal processing deficits. Further, effects of perinatal health risk on inattention, hyperactivity-impulsivity, and ODD were mediated by deficits in response variability and temporal processing. Further, maternal health risks during pregnancy appeared to exert direct rather than indirect effects on outcomes. Results suggest that after controlling for familial relatedness of ADHD between parent and child, early developmental health risks may influence ADHD via effects on neuropsychological processes underpinning the disorder.

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

Mendelian Randomization.

PubMed

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

2017-01-01

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

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.

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

PubMed

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

2004-05-01

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

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.

The oncogenic transforming potential of the passage of single α particles through mammalian cell nuclei

PubMed Central

Miller, Richard C.; Randers-Pehrson, Gerhard; Geard, Charles R.; Hall, Eric J.; Brenner, David J.

1999-01-01

Domestic, low-level exposure to radon gas is considered a major environmental lung-cancer hazard involving DNA damage to bronchial cells by α particles from radon progeny. At domestic exposure levels, the relevant bronchial cells are very rarely traversed by more than one α particle, whereas at higher radon levels—at which epidemiological studies in uranium miners allow lung-cancer risks to be quantified with reasonable precision—these bronchial cells are frequently exposed to multiple α-particle traversals. Measuring the oncogenic transforming effects of exactly one α particle without the confounding effects of multiple traversals has hitherto been unfeasible, resulting in uncertainty in extrapolations of risk from high to domestic radon levels. A technique to assess the effects of single α particles uses a charged-particle microbeam, which irradiates individual cells or cell nuclei with predefined exact numbers of particles. Although previously too slow to assess the relevant small oncogenic risks, recent improvements in throughput now permit microbeam irradiation of large cell numbers, allowing the first oncogenic risk measurements for the traversal of exactly one α particle through a cell nucleus. Given positive controls to ensure that the dosimetry and biological controls were comparable, the measured oncogenicity from exactly one α particle was significantly lower than for a Poisson-distributed mean of one α particle, implying that cells traversed by multiple α particles contribute most of the risk. If this result applies generally, extrapolation from high-level radon risks (involving cellular traversal by multiple α particles) may overestimate low-level (involving only single α particles) radon risks. PMID:9874764

Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

PubMed Central

Nelson, Suchitra; Albert, Jeffrey M.

2013-01-01

Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

PubMed

Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

2013-10-30

Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

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

PubMed

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

2015-03-15

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

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.

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.

Identifying Priorities for Mental Health Interventions in War-Affected Youth: A Longitudinal Study.

PubMed

Betancourt, Theresa S; Gilman, Stephen E; Brennan, Robert T; Zahn, Ista; VanderWeele, Tyler J

2015-08-01

War-affected youth often suffer from multiple co-occurring mental health problems. These youth often live in low-resource settings where it may be infeasible to provide mental health services that simultaneously address all of these co-occurring mental health issues. It is therefore important to identify the areas where targeted interventions would do the most good. This analysis uses observational data from 3 waves of a longitudinal study on mental health in a sample of 529 war-affected youth (24.2% female; ages 10-17 at T1, 2002) in Sierra Leone. We regressed 4 mental health outcomes at T3 (2008) on internalizing (depression/anxiety) and externalizing (hostility/aggression) problems and prosocial attitudes/behaviors and community variables at T2 (2004) controlling for demographics, war exposures, and previous mental health scores at T1, allowing us to assess the relative impact of potential mental health intervention targets in shaping mental health outcomes over time. Controlling for baseline covariates at T1 and all other exposures/potential intervention targets at T2, we observed a significant association between internalizing problems at T2 and 3 of the 4 outcomes at T3: internalizing (β = 0.27, 95% confidence interval [CI]: 0.11-0.42), prosocial attitudes (β = -0.20, 95% CI: -0.33 to -0.07) and posttraumatic stress symptoms (β = 0.22, 95% CI: 0.02-0.43). No other potential intervention target had similar substantial effects. Reductions in internalizing may have multiple benefits for other mental health outcomes at a later point in time, even after controlling for confounding variables. Copyright © 2015 by the American Academy of Pediatrics.

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.

Are attractive men's faces masculine or feminine? The importance of controlling confounds in face stimuli.

PubMed

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

2010-06-01

Women's preferences for male masculinity are highly variable. Although many researchers explain this variability as reflecting systematic individual differences in how women resolve the tradeoff between the costs and benefits of choosing a masculine partner, others suggest that methodological differences between studies are responsible. A recent study found general femininity preferences for judgments of faces that were manipulated in sexual dimorphism of shape but general masculinity preferences for judgments of faces that were based on perceived masculinity. Using the original stimuli, we replicated these previous results but found equivalent general femininity preferences for both types of faces when nonface confounds in the stimuli (e.g. hairstyle) were eliminated through masking. We conclude that care must be taken to control potential confounds in stimuli and that the influence of nonface cues on preferences for facial masculinity deserves further study.

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

PubMed

Lee, Peter N

2015-03-20

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

Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis.

PubMed

Galvez-Buccollini, Juan A; Proal, Ashley C; Tomaselli, Veronica; Trachtenberg, Melissa; Coconcea, Cristinel; Chun, Jinsoo; Manschreck, Theo; Fleming, Jerry; Delisi, Lynn E

2012-08-01

Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs. Fifty-seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables. After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (β=0.4, 95% CI=0.1-0.7, p=0.004) and age at first hospitalization (β=0.4, 95% CI=0.1-0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0±4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization. Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time. Published by Elsevier B.V.

Elevated serum complement C3 levels are related to the development of prediabetes in an adult population: the Tianjin Chronic Low-Grade Systematic Inflammation and Health Cohort Study.

PubMed

Bao, X; Xia, Y; Zhang, Q; Wu, H M; Du, H M; Liu, L; Wang, C J; Shi, H B; Guo, X Y; Liu, X; Li, C L; Su, Q; Meng, G; Yu, B; Sun, S M; Wang, X; Zhou, M; Jia, Q Y; Song, K; Niu, K J

2016-04-01

To investigate whether serum complement C3 is related to the prevalence and incidence of prediabetes in an adult population. A cross-sectional (n = 10 206) and prospective cohort study (n = 3333), with a mean (range; 95% CI) follow-up of 2.63 (1-6; 2.58-2.68) years, was conducted in people recruited from the Health Management Centre of Tianjin Medical University General Hospital in Tianjin, China. Measurement of serum C3 concentration, blood fasting glucose, oral glucose tolerance, HbA1c and other potential confounding factors was performed at baseline and each year during the follow-up. Prediabetes was defined according to the criteria of the American Diabetes Association. Adjusted logistic and Cox proportional hazards regression models were used to assess the relationships between C3 quintiles and prediabetes. The prevalence and incidence of prediabetes were 38.5% and 119 per 1000 person-years, respectively. In cross-sectional analysis, after adjustment for potential confounders, the odds ratios of prediabetes for increasing quintiles of C3 were 1.00 (reference), 1.32 (95% CI 1.14-1.53), 1.37 (95% CI 1.18-1.59), 1.75 (95% CI 1.51-2.03), 2.25 (95% CI 1.93-2.62; P for trend < 0.0001). In the cohort analysis, the multiple-adjusted hazard ratio of prediabetes in the highest quintile of baseline C3 was 1.43 (95% CI 1.15, 1.78; P for trend < 0.001), when compared with the lowest quintile. These findings indicate that elevated serum C3 levels are significantly related to an increased risk of developing prediabetes in an adult population, suggesting that C3 can be used as a biomarker in high-risk individuals to improve primary prevention of prediabetes and diabetes. © 2015 Diabetes UK.

Sexual satisfaction in females with premenstrual symptoms.

PubMed

Nowosielski, Krzysztof; Drosdzol, Agnieszka; Skrzypulec, Violetta; Plinta, Ryszard

2010-11-01

The impact of premenstrual symptoms, such as the premenstrual syndrome (PMS) and the premenstrual dysphoric disorder (PMDD), on sexual satisfaction, sexual distress, and sexual behaviors has not yet been established. To assess the correlates and risk factors of sexual satisfaction and to evaluate sexual behaviors among Polish women with premenstrual symptoms. 2,500 females, aged 18 to 45 years, from the Upper Silesian region of Poland were eligible for the questionnaire-based, prospective population study. All the inclusion criteria were met by 1,540 women who constituted the final study group. The participants were further divided into two subgroups: PMS+ (749 females) and PMS- (791 healthy subjects). Two additional subgroups were created: PMDD+ encompassing 32 subjects diagnosed with PMDD, and PMDD- comprising 32 healthy women, matched to the PMDD+ females for age, marital status, education level, employment status, place of living, and body mass index. A multiple logistic regression analysis was performed to evaluate the influence of PMS on sexual satisfaction and adjust for potential confounders. To evaluate risk factors for sexual dissatisfaction in a population of Polish females of reproductive age, diagnosed with PMS and PMDD. Women from the PMS+ group were less sexually satisfied than PMS- (77.73% vs. 88.66%, P=0.001) and reported more sexual distress (28.65% vs. 15.24%, P=0.001). There were no significant differences in sexual satisfaction between PMDD- and PMDD+. Sexual satisfaction correlated positively with a higher frequency of sexual intercourses and a higher level of education. The presence of PMS correlated negatively with sexual satisfaction, even after adjusting for potential confounders in the multivariate logistic regression model (odds ratio=0.48; confidence interval: 0.26-0.89; P=0.02). The presence of PMS is a risk factor for sexual dissatisfaction in Polish women of reproductive age. © 2010 International Society for Sexual Medicine.

Second-generation corneal deformation signal waveform analysis in normal, forme fruste keratoconic, and manifest keratoconic corneas after statistical correction for potentially confounding factors.

PubMed

Zhang, Lijun; Danesh, Jennifer; Tannan, Anjali; Phan, Vivian; Yu, Fei; Hamilton, D Rex

2015-10-01

To evaluate the difference in corneal biomechanical waveform parameters between manifest keratoconus, forme fruste keratoconus, and healthy eyes with a second-generation biomechanical waveform analyzer (Ocular Response Analyzer 2). Jules Stein Eye Institute, University of California, Los Angeles, California, USA. Retrospective chart review. The biomechanical waveform analyzer was used to obtain corneal hysteresis (CH), corneal resistance factor (CRF), and 37 biomechanical waveform parameters in manifest keratoconus eyes, forme fruste keratoconus eyes, and healthy eyes. Useful distinguishing parameters were found using t tests and a multivariable logistic regression model with stepwise variable selection. Potential confounders were controlled for. The study included 68 manifest keratoconus eyes, 64 forme fruste keratoconus eyes, and 249 healthy eyes. There was a statistical difference in the mean CRF between the normal group (10.2 mm Hg ± 1.7 [SD]) and keratoconus group (6.3 ± 1.9 mm Hg) (P = .003), and between the normal group and the forme fruste keratoconus group (7.8 ± 1.4 mm Hg) (P < .0001). There was no statistical difference in the mean CH between the normal group and the keratoconus group or the forme fruste keratoconus group. The CRF, height of peak 1 (P1) (P = .001), downslope of P1 (dslope1) (P = .027), upslope of peak 2 (P2) (P = .004), and downslope of P2 (P = .006) distinguished the normal group from the keratoconus groups. The CRF, downslope of P2 derived from upper 50% of applanation peak (P = .035), dslope1 (P = .014), and upslope of P1 (P = .008) distinguished the normal group from the forme fruste keratoconus group. Differences in multiple biomechanical waveform parameters can differentiate between healthy and diseased conditions and might improve early diagnosis of keratoconus and forme fruste keratoconus. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Blocker, Tomica D.; Ophir, Alexander G.

2012-01-01

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

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.

A powerful and efficient set test for genetic markers that handles confounders

PubMed Central

Listgarten, Jennifer; Lippert, Christoph; Kang, Eun Yong; Xiang, Jing; Kadie, Carl M.; Heckerman, David

2013-01-01

Motivation: Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger datasets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects—one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured Genetic Analysis Workshop 14 data demonstrates that our method successfully corrects for population structure and family relatedness, whereas application of our method to a 15 000 individual Crohn’s disease case–control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http://mscompbio.codeplex.com. Contact: jennl@microsoft.com or lippert@microsoft.com or heckerma@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23599503

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

PubMed Central

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

2011-01-01

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

Infant developmental milestones and adult intelligence: A 34-year follow-up.

PubMed

Flensborg-Madsen, Trine; Mortensen, Erik Lykke

2015-07-01

A number of studies suggest a positive association between faster infant motor development and intellectual function in childhood and adolescence. However, studies investigating the relationship between infant motor development and intelligence in adulthood are lacking. To investigate whether age at achievement of 12 motor developmental milestones was associated with adult intelligence and to evaluate the influence of sex, parental social status, parity, mother's cigarette consumption in the last trimester, gestational age, birthweight, and birth length on this association. Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year of life. A subsample of the cohort comprising 1155 individuals participated in a follow-up when they were aged 20-34 years and were administered the Wechsler Adult Intelligence Scale (WAIS). Associations between motor developmental milestones and IQ were analysed by multiple linear regression adjusting for potential confounding factors. Later acquisition of infant developmental milestones was associated with lower subsequent IQ, and the majority of significant associations were found for Performance IQ. Correlations were generally small (r < 0.10), but significant interactions were found between parental social status and age of attaining developmental milestones, with associations being significantly stronger in the offspring of lower social status parents. The effects remained significant after adjusting for possible confounding factors. This is the first study to find significant interactions with parental social status, thereby suggesting that associations between early motor development and intelligence are stronger in infants of low social status parents. Copyright © 2015 Elsevier B.V. All rights reserved.

Long-Term Neurodevelopmental Outcome after Doxapram for Apnea of Prematurity.

PubMed

Ten Hove, Christine H; Vliegenthart, Roseanne J; Te Pas, Arjan B; Brouwer, Emma; Rijken, Monique; van Wassenaer-Leemhuis, Aleid G; van Kaam, Anton H; Onland, Wes

2016-01-01

Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. From a retrospective cohort of preterm infants with a gestational age (GA) <30 weeks and/or a birth weight <1,250 g, born between 2000 and 2010, infants treated with doxapram (n = 142) and a nontreated control group were selected (n = 284). Patient characteristics and clinical and neurodevelopmental outcome data at 24 months' corrected age were collected. Neurodevelopmental delay (ND) was defined as having a Mental or Psychomotor Developmental Index (MDI/PDI) <-1 standard deviation (SD), cerebral palsy, or a hearing or visual impairment. Odds ratios (OR) were calculated using multiple logistic regression analyses adjusting for potential confounders. Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI <-1 SD was not different between the groups. The risk of the combined outcome death or ND was significantly lower in the doxapram group after adjusting for confounding factors (OR = 0.54, 95% CI: 0.37, 0.78). Doxapram-treated infants had a higher risk of bronchopulmonary dysplasia and patent ductus arteriosus, but a lower risk of spontaneous intestinal perforation. All other morbidities were not different between the groups. This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial. © 2016 The Author(s) Published by S. Karger AG, Basel.

Spending more money, saving more lives? The relationship between avoidable mortality and healthcare spending in 14 countries.

PubMed

Heijink, Richard; Koolman, Xander; Westert, Gert P

2013-06-01

Healthcare expenditures rise as a share of GDP in most countries, raising questions regarding the value of further spending increases. Against this backdrop, we assessed the value of healthcare spending growth in 14 western countries between 1996 and 2006. We estimated macro-level health production functions using avoidable mortality as outcome measure. Avoidable mortality comprises deaths from certain conditions "that should not occur in the presence of timely and effective healthcare". We investigated the relationship between total avoidable mortality and healthcare spending using descriptive analyses and multiple regression models, focussing on within-country variation and growth rates. We aimed to take into account the role of potential confounders and dynamic effects such as time lags. Additionally, we explored a method to estimate macro-level cost-effectiveness. We found an average yearly avoidable mortality decline of 2.6-5.3% across countries. Simultaneously, healthcare spending rose between 1.9 and 5.9% per year. Most countries with above-average spending growth demonstrated above-average reductions in avoidable mortality. The regression models showed a significant association between contemporaneous and lagged healthcare spending and avoidable mortality. The time-trend, representing an exogenous shift of the health production function, reduced the impact of healthcare spending. After controlling for this time-trend and other confounders, i.e. demographic and socioeconomic variables, a statistically significant relationship between healthcare spending and avoidable mortality remained. We tentatively conclude that macro-level healthcare spending increases provided value for money, at least for the disease groups, countries and years included in this study.

Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways

PubMed Central

Burgess, Stephen; Daniel, Rhian M; Butterworth, Adam S; Thompson, Simon G

2015-01-01

Background: Mendelian randomization uses genetic variants, assumed to be instrumental variables for a particular exposure, to estimate the causal effect of that exposure on an outcome. If the instrumental variable criteria are satisfied, the resulting estimator is consistent even in the presence of unmeasured confounding and reverse causation. Methods: We extend the Mendelian randomization paradigm to investigate more complex networks of relationships between variables, in particular where some of the effect of an exposure on the outcome may operate through an intermediate variable (a mediator). If instrumental variables for the exposure and mediator are available, direct and indirect effects of the exposure on the outcome can be estimated, for example using either a regression-based method or structural equation models. The direction of effect between the exposure and a possible mediator can also be assessed. Methods are illustrated in an applied example considering causal relationships between body mass index, C-reactive protein and uric acid. Results: These estimators are consistent in the presence of unmeasured confounding if, in addition to the instrumental variable assumptions, the effects of both the exposure on the mediator and the mediator on the outcome are homogeneous across individuals and linear without interactions. Nevertheless, a simulation study demonstrates that even considerable heterogeneity in these effects does not lead to bias in the estimates. Conclusions: These methods can be used to estimate direct and indirect causal effects in a mediation setting, and have potential for the investigation of more complex networks between multiple interrelated exposures and disease outcomes. PMID:25150977

Impact of maternal work outside the home during pregnancy on neonatal outcome.

PubMed

Zuckerman, B S; Frank, D A; Hingson, R; Morelock, S; Kayne, H L

1986-04-01

The impact of mothers' work during pregnancy upon neonatal outcome has not been fully elucidated. A study of maternal health habits and neonatal outcome conducted from 1977 to 1979 at Boston City Hospital assessed the effects of paid work outside the home during pregnancy, particularly third trimester work in a standing position, upon duration of gestation and intrauterine growth, while controlling for potentially confounding variables. Postpartum, 1,690 low-income women were interviewed to provide detailed information on their sociodemographic and health characteristics. Of the 1,507 women whose work status during pregnancy could be classified, 55% did not perform paid work outside the home or attend school, 7% worked into the third trimester in a standing position, and 38% had other work histories or attended school. Infants were examined according to a standard protocol by pediatricians blind to mothers' work history. There was no significant relationship between the mothers' work history during pregnancy and the infants' length of gestation, weight, or head circumference at birth, when confounding variables were controlled statistically by multiple regression analyses. However, women who worked in a standing position into the third trimester delivered infants who were longer than infants born either to mothers with other work histories or to mothers who did not work or attend school. Healthy women with uncomplicated low-risk pregnancies who feel well enough to attend school or work during pregnancy, even in a job requiring some standing, may do so without fear that their infant will suffer shortened gestation or impaired intrauterine growth.

Asthma and mental health among youth in high-risk service settings.

PubMed

Goodwin, Renee D; Hottinger, Kate; Pena, Lillian; Chacko, Anil; Feldman, Jonathan; Wamboldt, Marianne Z; Hoven, Christina

2014-08-01

To investigate the prevalence of asthma and mental health problems among representative samples of youth in high-risk service settings and the community, and to examine the relationship between asthma and mental health in these groups. Data were drawn from the Alternative Service Use Patterns of Youth with Serious Emotional Disturbance Study (SED) (n = 1181), a combined representative, cross-sectional sample of youth in various clinical settings and the community. Multiple logistic regression analyses were used to examine the association between asthma and mental disorders. Demographic characteristics were investigated as potential confounders. Asthma was common among 15.2% of youth in service settings and 18.8% of youth in the community. The prevalence of mental disorders was extremely high among youth with and without asthma in all service settings, and asthma was associated with increased prevalence of mental disorders among youth in the community, but not among youth in service settings. The relationship between asthma and internalizing disorders among youth in the community does not appear entirely attributable to confounding by demographics. Findings are consistent with and extend previous data by showing that both asthma and mental disorders are disproportionately common among youth in high-risk service settings. Almost half of youth with asthma in service settings meet diagnostic criteria for a mental disorder. Clinicians and policy makers who are responsible for the health care of youth in these high-risk groups should be aware that asthma is common, and that the prevalence of internalizing disorders are especially common among those with asthma.

Delayed introduction of solid feeding reduces child overweight and obesity at 10 years.

PubMed

Seach, K A; Dharmage, S C; Lowe, A J; Dixon, J B

2010-10-01

The function that the timing of introduction of solid foods may have in the development of child obesity has not been adequately explored, either as a potential confounder of the relationship between breastfeeding and child obesity, or as an independent modifiable risk factor. To determine the association between infant feeding practices and child overweight/obesity. Six hundred and twenty subjects were recruited antenatally from 1990 to 1994. A total of 18 telephone interviews over the first 2 years of life recorded infant feeding practices. At mean age of 10 years, height and weight were measured for 307 subjects. Multiple logistic regression was used to determine whether infant feeding practices (duration of exclusive and any breastfeeding, and age at introduction of solid foods) were associated with odds of being overweight/obese (internationally age- and sex-standardized body mass index category) at age 10 years, after adjustment for confounders. Delayed introduction of solid foods was associated with reduced odds of being overweight/obese at age 10 years, after controlling for socioeconomic status, parental smoking and childcare attendance (adjusted odds ratio (aOR)=0.903 per week, 95% CI=0.841-0.970, P=0.005). Antenatal parental smoking was associated with overweight/obesity at age 10 years (aOR=3.178, 95% CI=1.643-6.147, P=0.001). Duration of exclusive or any breastfeeding was not associated with the outcome. Delayed introduction of solids is associated with reduced odds of child overweight/obesity. Wider promotion of current infant feeding guidelines could have a significant impact on the rates of child overweight and obesity.

A quantitative approach to assessing the efficacy of occupant protection programs: A case study from Montana.

PubMed

Manlove, Kezia; Stanley, Laura; Peck, Alyssa

2015-10-01

Quantitative evaluation of vehicle occupant protection programs is critical for ensuring efficient government resource allocation, but few methods exist for conducting evaluation across multiple programs simultaneously. Here we present an analysis of occupant protection efficacy in the state of Montana. This approach relies on seat belt compliance rates as measured by the National Occupant Protection Usage Survey (NOPUS). A hierarchical logistic regression model is used to estimate the impacts of four Montana Department of Transportation (MDT)-funded occupant protection programs used in the state of Montana, following adjustment for a suite of potential confounders. Activity from two programs, Buckle Up coalitions and media campaigns, are associated with increased seat belt use in Montana, whereas the impact of another program, Selective Traffic Enforcement, is potentially masked by other program activity. A final program, Driver's Education, is not associated with any shift in seat belt use. This method allows for a preliminary quantitative estimation of program impacts without requiring states to obtain any new seat belt use data. This approach provides states a preliminary look at program impacts, and a means for carefully planning future program allocation and investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Independent association of clustered metabolic risk factors with cardiorespiratory fitness in youth aged 11-17 years.

PubMed

Machado-Rodrigues, Aristides M; Leite, Neiva; Coelho-e-Silva, Manuel J; Martins, Raul A; Valente-dos-Santos, João; Mascarenhas, Luís P G; Boguszewski, Margaret C S; Padez, Cristina; Malina, Robert M

2014-01-01

Although the prevalence of metabolic syndrome (MetS) has increased in youth, the potential independent contribution of cardiorespiratory fitness (CRF) to the clustering of metabolic risk factors has received relatively little attention. This study evaluated associations between the clustering of metabolic risk factors and CRF in a sample of youth. Height, weight, BMI, fasting glucose, insulin, HDL-cholesterol, triglycerides and blood pressures were measured in a cross-sectional sample of 924 youth (402 males, 522 females) of 11-17 years. CRF was assessed using the 20-metre shuttle run test. Physical activity (PA) was measured with a 3-day diary. Outcome variables were statistically normalized and expressed as Z-scores. A MetS risk score was computed as the mean of the Z-scores. Multiple linear regression was used to test associations between CRF and metabolic risk, adjusted for age, sex, BMI, PA and parental education. CRF was inversely associated with MetS after adjustment for potential confounders. After adjusting for BMI, the relationship between CRF and metabolic risk has substantially improved. CRF was independently associated with the clustering of metabolic risk factors in youth of 11-17 years of age.

Urinary concentrations of PAH and VOC metabolites in marijuana users.

PubMed

Wei, Binnian; Alwis, K Udeni; Li, Zheng; Wang, Lanqing; Valentin-Blasini, Liza; Sosnoff, Connie S; Xia, Yang; Conway, Kevin P; Blount, Benjamin C

2016-03-01

Marijuana is seeing increased therapeutic use, and is the world's third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p<0.05). Urinary thiocyanate (p<0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p<0.001) and acrylamide (p<0.001), were significantly higher in recent marijuana users than in nonusers. We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. Published by Elsevier Ltd.

Urinary concentrations of PAH and VOC metabolites in marijuana users

PubMed Central

Wei, Binnian; Alwis, K. Udeni; Li, Zheng; Wang, Lanqing; Valentin-Blasini, Liza; Sosnoff, Connie S.; Xia, Yang; Conway, Kevin P.; Blount, Benjamin C.

2016-01-01

Background Marijuana is seeing increased therapeutic use, and is the world’s third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. Objectives To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Methods Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18 years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Results Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p < 0.05). Urinary thiocyanate (p < 0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p < 0.001) and acrylamide (p < 0.001), were significantly higher in recent marijuana users than in nonusers. Conclusions We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. PMID:26690539

Understanding the delayed-keyword effect on metacomprehension accuracy.

PubMed

Thiede, Keith W; Dunlosky, John; Griffin, Thomas D; Wiley, Jennifer

2005-11-01

The typical finding from research on metacomprehension is that accuracy is quite low. However, recent studies have shown robust accuracy improvements when judgments follow certain generation tasks (summarizing or keyword listing) but only when these tasks are performed at a delay rather than immediately after reading (K. W. Thiede & M. C. M. Anderson, 2003; K. W. Thiede, M. C. M. Anderson, & D. Therriault, 2003). The delayed and immediate conditions in these studies confounded the delay between reading and generation tasks with other task lags, including the lag between multiple generation tasks and the lag between generation tasks and judgments. The first 2 experiments disentangle these confounded manipulations and provide clear evidence that the delay between reading and keyword generation is the only lag critical to improving metacomprehension accuracy. The 3rd and 4th experiments show that not all delayed tasks produce improvements and suggest that delayed generative tasks provide necessary diagnostic cues about comprehension for improving metacomprehension accuracy.

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

PubMed

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

2016-01-01

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

Impact of mode of transportation on dyslipidaemia in working people in Beijing.

PubMed

Guo, X; Jia, Z; Zhang, P; Yang, S; Wu, W; Sang, L; Luo, Y; Lu, X; Dai, H; Zeng, Z; Wang, W

2009-12-01

This study aims to investigate the association between mode of transportation to work and dyslipidaemia. During the period between January and February 2006, telephone interviews were conducted with 2506 randomly selected urban residents aged 18 years or older in the 8 districts of Beijing, using a multiple stratified random sampling technique. Of the selected individuals, 1024 (40.86%) members of the workforce were subsequently tested for biomarkers (ie, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)). Multiple logistic regression modelling was used, adjusted for potential confounders. The probability of dyslipidaemia in workers who travel to work by bus, car or taxi is higher than that of workers who walk to work, with prevalence odds ratios (PORs) of 1.99 (95% CI 1.33 to 2.97) and 2.21 (95% CI 1.28 to 3.84), respectively. There is no significant difference in the risk of experiencing dyslipidaemia when workers who ride bicycles are compared with those who walk to work (POR = 1.22, 95% CI 0.83 to 1.78). These findings indicate that modes of transportation to work are significantly associated with the prevalence of dyslipidaemia. Prevention education should be emphasised among higher-risk people who usually go to work by car, bus or taxi.

Decreased pain sensitivity due to trimethylbenzene exposure ...

EPA Pesticide Factsheets

Traditionally, human health risk assessments have relied on qualitative approaches for hazard identification, often using the Hill criteria and weight of evidence determinations to integrate data from multiple studies. Recently, the National Research Council has recommended the development of quantitative approaches for evidence integration, including the application of meta-analyses. The following hazard identification case study applies qualitative as well as meta-analytic approaches to trimethylbenzene (TMB) isomers exposure and the potential neurotoxic effects on pain sensitivity. In the meta-analytic approach, a pooled effect size is calculated, after consideration of multiple confounding factors, in order to determine whether the entire database under consideration indicates that TMBs are likely to be a neurotoxic hazard. The pain sensitivity studies included in the present analyses initially seem discordant in their results: effects on pain sensitivity are seen immediately after termination of exposure, appear to resolve 24 hours after exposure, and then reappear 50 days later following foot-shock. Qualitative consideration of toxicological and toxicokinetic characteristics of the TMB isomers suggests that the observed differences between studies are due to testing time and can be explained through a complete consideration of the underlying biology of the effect and the nervous system as a whole. Meta-analyses and –regressions support this conclus

Sequential Monte Carlo tracking of the marginal artery by multiple cue fusion and random forest regression.

PubMed

Cherry, Kevin M; Peplinski, Brandon; Kim, Lauren; Wang, Shijun; Lu, Le; Zhang, Weidong; Liu, Jianfei; Wei, Zhuoshi; Summers, Ronald M

2015-01-01

Given the potential importance of marginal artery localization in automated registration in computed tomography colonography (CTC), we have devised a semi-automated method of marginal vessel detection employing sequential Monte Carlo tracking (also known as particle filtering tracking) by multiple cue fusion based on intensity, vesselness, organ detection, and minimum spanning tree information for poorly enhanced vessel segments. We then employed a random forest algorithm for intelligent cue fusion and decision making which achieved high sensitivity and robustness. After applying a vessel pruning procedure to the tracking results, we achieved statistically significantly improved precision compared to a baseline Hessian detection method (2.7% versus 75.2%, p<0.001). This method also showed statistically significantly improved recall rate compared to a 2-cue baseline method using fewer vessel cues (30.7% versus 67.7%, p<0.001). These results demonstrate that marginal artery localization on CTC is feasible by combining a discriminative classifier (i.e., random forest) with a sequential Monte Carlo tracking mechanism. In so doing, we present the effective application of an anatomical probability map to vessel pruning as well as a supplementary spatial coordinate system for colonic segmentation and registration when this task has been confounded by colon lumen collapse. Published by Elsevier B.V.

The evolution of primate general and cultural intelligence

PubMed Central

Reader, Simon M.; Hager, Yfke; Laland, Kevin N.

2011-01-01

There are consistent individual differences in human intelligence, attributable to a single ‘general intelligence’ factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, ‘primate gS’, covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support ‘massive modularity’ in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes. PMID:21357224

The Confounding Effects of Ability, Item Difficulty, and Content Balance within Multiple Dimensions on the Estimation of Unidimensional Thetas

ERIC Educational Resources Information Center

Matlock, Ki Lynn

2013-01-01

When test forms that have equal total test difficulty and number of items vary in difficulty and length within sub-content areas, an examinee's estimated score may vary across equivalent forms, depending on how well his or her true ability in each sub-content area aligns with the difficulty of items and number of items within these areas.…

Analyzing self-controlled case series data when case confirmation rates are estimated from an internal validation sample.

PubMed

Xu, Stanley; Clarke, Christina L; Newcomer, Sophia R; Daley, Matthew F; Glanz, Jason M

2018-05-16

Vaccine safety studies are often electronic health record (EHR)-based observational studies. These studies often face significant methodological challenges, including confounding and misclassification of adverse event. Vaccine safety researchers use self-controlled case series (SCCS) study design to handle confounding effect and employ medical chart review to ascertain cases that are identified using EHR data. However, for common adverse events, limited resources often make it impossible to adjudicate all adverse events observed in electronic data. In this paper, we considered four approaches for analyzing SCCS data with confirmation rates estimated from an internal validation sample: (1) observed cases, (2) confirmed cases only, (3) known confirmation rate, and (4) multiple imputation (MI). We conducted a simulation study to evaluate these four approaches using type I error rates, percent bias, and empirical power. Our simulation results suggest that when misclassification of adverse events is present, approaches such as observed cases, confirmed case only, and known confirmation rate may inflate the type I error, yield biased point estimates, and affect statistical power. The multiple imputation approach considers the uncertainty of estimated confirmation rates from an internal validation sample, yields a proper type I error rate, largely unbiased point estimate, proper variance estimate, and statistical power. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fertility and HIV following universal access to ART in Rwanda: a cross-sectional analysis of Demographic and Health Survey data.

PubMed

Remera, Eric; Boer, Kimberly; Umuhoza, Stella M; Hedt-Gauthier, Bethany L; Thomson, Dana R; Ndimubanzi, Patrick; Kayirangwa, Eugenie; Mutsinzi, Salomon; Bayingana, Alice; Mugwaneza, Placidie; Koama, Jean Baptiste T

2017-03-14

HIV infection is linked to decreased fertility and fertility desires in sub-Saharan Africa due to biological and social factors. We investigate the relationship between HIV infection and fertility or fertility desires in the context of universal access to antiretroviral therapy introduced in 2004 in Rwanda. We used data from 3532 and 4527 women aged 20-49 from the 2005 and 2010 Rwandan Demographic and Health Surveys (RDHS), respectively. The RDHSs included blood-tests for HIV, as well as detailed interviews about fertility, demographic and behavioral outcomes. In both years, multiple logistic regression was used to assess the association between HIV and fertility outcomes within three age categories (20-29, 30-39 and 40-49 years), controlling for confounders and compensating for the complex survey design. In 2010, we did not find a difference in the odds of pregnancy in the last 5 years between HIV-seropositive and HIV-seronegative women after controlling for potential biological and social confounders. Controlling for the same confounders, we found that HIV-seropositive women under age 40 were less likely to desire more children compared to HIV-seronegative women (20-29 years adjusted odds ratio (AOR) = 0.31, 95% CI: 0.17, 0.58; 30-39 years AOR = 0.24, 95% CI: 0.14, 0.43), but no difference was found among women aged 40 or older. No associations between HIV and fertility or fertility desire were found in 2005. These findings suggest no difference in births or current pregnancy among HIV-seropositive and HIV-seronegative women. That in 2010 HIV-seropositive women in their earlier childbearing years desired fewer children than HIV-seronegative women could suggest more women with HIV survived; and stigma, fear of transmitting HIV, or realism about living with HIV and prematurely dying from HIV may affect their desire to have children. These findings emphasize the importance of delivering appropriate information about pregnancy and childbearing to HIV-infected women, enabling women living with HIV to make informed decisions about their reproductive life.

Disparities in cervical screening participation: a comparison of Russian, Somali and Kurdish immigrants with the general Finnish population.

PubMed

Idehen, Esther E; Koponen, Päivikki; Härkänen, Tommi; Kangasniemi, Mari; Pietilä, Anna-Maija; Korhonen, Tellervo

2018-05-04

Cervical cancer is currently ranked as the fourth commonly diagnosed cancer in women globally. A higher incidence has been reported in low- and-middle-income countries, and the disease poses significant public health challenges. Evidence suggests that this disease is preventable by means of regular screening using the Papanicolaou (Pap) test. However, limited knowledge exists about disparities in cervical screening participation among immigrants compared with non-immigrants, in countries with universal cervical screening programmes. We aimed to examine disparities in cervical screening participation among women of Russian, Somali, and Kurdish, origin in Finland, comparing them with the general Finnish population (Finns). We controlled for differences in several socio-demographic and health-related variables as potential confounders. We employed data from the Finnish Migrant Health and Well-being Study 2010-2012 and the National Health 2011 Survey. Data collection involved face-to-face interviews. Data on screening participation in the previous five years from women aged 29-60 were available from 537 immigrants (257 Russians, 113 Somalis, 167 Kurds) and from 436 Finns. For statistical analyses, we used multiple logistic regression. Age-adjusted screening participation rates were as follows: Russians 79% (95% CI 72.9-84.4), Somalis 41% (95% CI 31.4-50.1), and Kurds 64% (95% CI 57.2-70.8), compared with 94% (95% CI 91.4-95.9) among Finns. After additionally adjusting for socio-demographic and health-related confounders, all the immigrant groups showed a significantly lower likelihood of screening participation when compared with Finns. The Odds Ratios were as follows: Russians 0.32 (95% CI 0.18-0.58), Somalis 0.10 (95% CI 0.04-0.23), and Kurds 0.17 (95% CI 0.09-0.35). However, when additionally accounting for country of origin-confounder interactions, such differences were attenuated. Our results indicate disparities in screening participation among these immigrants and a lower likelihood of screening participation compared with the general Finnish population. To improve equity in cervical cancer screening participation, appropriate culturally tailored intervention programmes for each immigrant group might be beneficial.

A New Radiofrequency Ablation Procedure to Treat Sacroiliac Joint Pain.

PubMed

Cheng, Jianguo; Chen, See Loong; Zimmerman, Nicole; Dalton, Jarrod E; LaSalle, Garret; Rosenquist, Richard

2016-01-01

Low back pain may arise from disorders of the sacroiliac joint in up to 30% of patients. Radiofrequency ablation (RFA) of the nerves innervating the sacroiliac joint has been shown to be a safe and efficacious strategy. We aimed to develop a new RFA technique to relieve low back pain secondary to sacroiliac joint disorders. Methodology development with validation through prospective observational non-randomized trial (PONRT). Academic multidisciplinary health care system, Ohio, USA. We devised a guide-block to facilitate accurate placement of multiple electrodes to simultaneously ablate the L5 dorsal ramus and lateral branches of the S1, S2, and S3 dorsal rami. This was achieved by bipolar radiofrequency ablation (b-RFA) to create a strip lesion from the lateral border of the base of the sacral superior articular process (L5-S1 facet joint) to the lateral border of the S3 sacral foramen. We applied this technique in 31 consecutive patients and compared the operating time, x-ray exposure time and dose, and clinical outcomes with patients (n = 62) who have been treated with the cooled radiofrequency technique. Patients' level of pain relief was reported as < 50%, 50 - 80%, and > 80% pain relief at one, 3, 6, and 12 months after the procedure. The relationship between RFA technique and duration of pain relief was evaluated using interval-censored multivariable Cox regression. The new technique allowed reduction of operating time by more than 50%, x-ray exposure time and dose by more than 80%, and cost by more than $1,000 per case. The percent of patients who achieved > 50% pain reduction was significantly higher in the b-RFA group at 3, 6, and 12 months follow-up, compared to the cooled radiofrequency group. No complications were observed in either group. Although the major confounding factors were taken into account in the analysis, use of historical controls does not balance observed and unobserved potential confounding variables between groups so that the reported results are potentially confounded. Compared to the cooled radiofrequency ablation (c-RFA) technique, the new b-RFA technique reduced operating time by more than 50%, decreased x-ray exposure by more than 80%, and cut the cost by more than $1000 per case. The new method was associated with significantly improved clinical outcomes despite the limitations of the study design. Thus this new technique appeared to be safe, efficacious, and cost-effective. Key words: Sacroiliac joint pain, sacroiliac joint, low back pain, radiofrequency ablation (RFA), bipolar radiofrequency ablation (b-RFA), cooled radiofrequency ablation (c-RFA), cost-effectiveness.

Vehicle year and the risk of car crash injury

PubMed Central

Blows, S; Ivers, R; Woodward, M; Connor, J; Ameratunga, S; Norton, R

2003-01-01

Objective: To quantify the association between vehicle age and risk of car crash injury. Design and setting: Data from a population based case-control study conducted in the Auckland region in 1998/99 was used to examine the adjusted risk of car crash injury or death due to vehicle age, after controlling for a range of known confounders. Cases were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and controls were randomly selected cars on Auckland roads. The drivers of the 571 case vehicles and 588 control vehicles completed a structured interview. Main outcome measure: Hospitalisation or death of a vehicle occupant due to car crash injury. Results: Vehicles constructed before 1984 had significantly greater chance of being involved in an injury crash than those constructed after 1994 (odds ratio 2.88, 95% confidence interval (CI) 1.20 to 6.91), after adjustment for potential confounders. There was also a trend for increasing crash risk with each one year increase in vehicle age after adjustment for potential confounders (odds ratio 1.05, 95% CI 0.99 to 1.11; p = 0.09). Conclusion: This study quantifies the increased risk of car crash injury associated with older vehicle year and confirms this as an important public health issue. PMID:14693899

Vehicle year and the risk of car crash injury.

PubMed

Blows, S; Ivers, R Q; Woodward, M; Connor, J; Ameratunga, S; Norton, R

2003-12-01

To quantify the association between vehicle age and risk of car crash injury. Data from a population based case-control study conducted in the Auckland region in 1998/99 was used to examine the adjusted risk of car crash injury or death due to vehicle age, after controlling for a range of known confounders. Cases were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and controls were randomly selected cars on Auckland roads. The drivers of the 571 case vehicles and 588 control vehicles completed a structured interview. Hospitalisation or death of a vehicle occupant due to car crash injury. Vehicles constructed before 1984 had significantly greater chance of being involved in an injury crash than those constructed after 1994 (odds ratio 2.88, 95% confidence interval (CI) 1.20 to 6.91), after adjustment for potential confounders. There was also a trend for increasing crash risk with each one year increase in vehicle age after adjustment for potential confounders (odds ratio 1.05, 95% CI 0.99 to 1.11; p = 0.09). This study quantifies the increased risk of car crash injury associated with older vehicle year and confirms this as an important public health issue.

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

PubMed

Garcia-Huidobro, Diego; Michael Oakes, J

2017-04-01

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

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

PubMed

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

2013-12-01

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

Memory complaints are related to Alzheimer disease pathology in older persons.

PubMed

Barnes, L L; Schneider, J A; Boyle, P A; Bienias, J L; Bennett, D A

2006-11-14

To study the relationship between Alzheimer disease (AD) pathology and memory complaints proximate to death. A group of 90 older persons underwent detailed clinical evaluations and brain autopsy at death. The evaluations included administration of questions on subjective memory complaints and clinical classification of dementia and AD. On postmortem examination, neuritic plaques, diffuse plaques, and neurofibrillary tangles in tissue samples from five cortical regions were counted, and a summary measure of overall AD pathology was derived. In addition, amyloid load and tau tangles were quantified in eight regions. In multiple linear regression models adjusted for age, sex, and education, memory complaints were associated with AD pathology, including both amyloid and tau tangles. Subsequent analyses demonstrated that the relationship between memory complaints and AD pathology was present in those with and without dementia, and could not be explained by the potentially confounding effects of depressive symptoms or coexisting common chronic health problems. Memory complaints in older persons may indicate self awareness of a degenerative process.

Revisiting Rossion and Pourtois with new ratings for automated complexity, familiarity, beauty, and encounter.

PubMed

Forsythe, Alex; Street, Nichola; Helmy, Mai

2017-08-01

Differences between norm ratings collected when participants are asked to consider more than one picture characteristic are contrasted with the traditional methodological approaches of collecting ratings separately for image constructs. We present data that suggest that reporting normative data, based on methodological procedures that ask participants to consider multiple image constructs simultaneously, could potentially confounded norm data. We provide data for two new image constructs, beauty and the extent to which participants encountered the stimuli in their everyday lives. Analysis of this data suggests that familiarity and encounter are tapping different image constructs. The extent to which an observer encounters an object predicts human judgments of visual complexity. Encountering an image was also found to be an important predictor of beauty, but familiarity with that image was not. Taken together, these results suggest that continuing to collect complexity measures from human judgments is a pointless exercise. Automated measures are more reliable and valid measures, which are demonstrated here as predicting human preferences.

Statistically Controlling for Confounding Constructs Is Harder than You Think

PubMed Central

Westfall, Jacob; Yarkoni, Tal

2016-01-01

Social scientists often seek to demonstrate that a construct has incremental validity over and above other related constructs. However, these claims are typically supported by measurement-level models that fail to consider the effects of measurement (un)reliability. We use intuitive examples, Monte Carlo simulations, and a novel analytical framework to demonstrate that common strategies for establishing incremental construct validity using multiple regression analysis exhibit extremely high Type I error rates under parameter regimes common in many psychological domains. Counterintuitively, we find that error rates are highest—in some cases approaching 100%—when sample sizes are large and reliability is moderate. Our findings suggest that a potentially large proportion of incremental validity claims made in the literature are spurious. We present a web application (http://jakewestfall.org/ivy/) that readers can use to explore the statistical properties of these and other incremental validity arguments. We conclude by reviewing SEM-based statistical approaches that appropriately control the Type I error rate when attempting to establish incremental validity. PMID:27031707

Association of financial and health literacy with cognitive health in old age.

PubMed

Wilson, Robert S; Yu, Lei; James, Bryan D; Bennett, David A; Boyle, Patricia A

2017-03-01

We tested the hypothesis that higher financial and health literacy is associated with better cognitive health in 755 older persons who completed a literacy measure (M = 67.9, SD = 14.5) and then had annual clinical evaluations for a mean of 3.4 years. In proportional hazards models, higher literacy was associated with decreased risk of developing incident Alzheimer's disease (n = 68) and results were similar for financial and health literacy subscales and after adjustment for potential confounders. In mixed-effects models, higher literacy was related to higher baseline level of cognition and reduced cognitive decline in multiple domains. Among the 602 persons without any cognitive impairment at baseline, higher literacy was associated with a reduced rate of cognitive decline and risk of developing incident mild cognitive impairment (n = 142). The results suggest that higher levels of financial and health literacy are associated with maintenance of cognitive health in old age.

Paleo-drainage basin connectivity predicts evolutionary relationships across three Southeast Asian biodiversity hotspots.

PubMed

de Bruyn, Mark; Rüber, Lukas; Nylinder, Stephan; Stelbrink, Björn; Lovejoy, Nathan R; Lavoué, Sébastien; Tan, Heok Hui; Nugroho, Estu; Wowor, Daisy; Ng, Peter K L; Siti Azizah, M N; Von Rintelen, Thomas; Hall, Robert; Carvalho, Gary R

2013-05-01

Understanding factors driving diversity across biodiversity hotspots is critical for formulating conservation priorities in the face of ongoing and escalating environmental deterioration. While biodiversity hotspots encompass a small fraction of Earth's land surface, more than half the world's plants and two-thirds of terrestrial vertebrate species are endemic to these hotspots. Tropical Southeast (SE) Asia displays extraordinary species richness, encompassing four biodiversity hotspots, though disentangling multiple potential drivers of species richness is confounded by the region's dynamic geological and climatic history. Here, we use multilocus molecular genetic data from dense multispecies sampling of freshwater fishes across three biodiversity hotspots, to test the effect of Quaternary climate change and resulting drainage rearrangements on aquatic faunal diversification. While Cenozoic geological processes have clearly shaped evolutionary history in SE Asian halfbeak fishes, we show that paleo-drainage re-arrangements resulting from Quaternary climate change played a significant role in the spatiotemporal evolution of lowland aquatic taxa, and provide priorities for conservation efforts.

Abnormal cardiac autonomic control in sickle cell disease following transient hypoxia.

PubMed

Sangkatumvong, Suvimol; Khoo, Michael C K; Coates, Thomas D

2008-01-01

Abnormalities in autonomic control in sickle cell anemia (SCA) patients have been reported by multiple researchers. However their potential causal association with sickle cell crisis remains unknown. We employed hypoxia, a known trigger to sickle cell crisis, to perturb the autonomic systems of the subjects. Cardiac autonomic control was non-invasively assessed by tracking the changes in heart rate variability (HRV) that occur following brief exposure to a hypoxia stimulus. Time varying spectral analysis of HRV was applied to estimate the cardiac autonomic response to the transient episode of hypoxia. The results demonstrate that cardiovascular autonomic response to hypoxia is substantially more sensitive in SCA than in normal controls. We also developed a model to compensate for the confounding effects of respiration on the HRV spectral indices by using the corresponding respiration signal to compensate for the respiratory correlated part of the HRV. This technique improved the resolution with which the effect of hypoxia on changes in HRV could be measured.

Histopathological Evaluation of Skeletal Muscle with Specific Reference to Mouse Models of Muscular Dystrophy.

PubMed

Terry, Rebecca L; Wells, Dominic J

2016-12-01

The muscular dystrophies are a diverse group of degenerative diseases for which many mouse models are available. These models are frequently used to assess potential therapeutic interventions and histological evaluation of multiple muscles is an important part of this assessment. Histological evaluation is especially useful when combined with tests of muscle function. This unit describes a protocol for necropsy, processing, cryosectioning, and histopathological evaluation of murine skeletal muscles, which is applicable to both models of muscular dystrophy and other neuromuscular conditions. Key histopathological features of dystrophic muscle are discussed using the mdx mouse (a model of Duchenne muscular dystrophy) as an example. Optimal handling during dissection, processing and sectioning is vital to avoid artifacts that can confound or prevent future analyses. Muscles carefully processed using this protocol are suitable for further evaluation using immunohistochemistry, immunofluorescence, special histochemical stains, and immuoblotting. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Familial Risk Moderates the Association Between Sleep and zBMI in Children

PubMed Central

El-Sheikh, Mona

2013-01-01

Objective A cumulative risk approach was used to examine the moderating effect of familial risk factors on relations between actigraphy-based sleep quantity (minutes) and quality (efficiency) and sex- and age-standardized body mass index (zBMI). Methods The sample included 124 boys and 104 girls with a mean age of 10.41 years (SD = 0.67). Children wore actigraphs for 1 week, and their height and weight were assessed in the lab. Results After controlling for potential confounds, multiple regression analyses indicated that sleep minutes predicted children’s zBMI and that both sleep minutes and efficiency interacted with family risk in the prediction of zBMI. The association between poor sleep and zBMI was especially evident for children exposed to higher levels of family risk. Conclusions Findings suggest that not all children who exhibit poor sleep are at equal risk for higher zBMI and that familial and contextual conditions need to be considered in this link. PMID:23699749

The Association Between 25 Hydroxyvitamin D and Airway Obstruction in Asthma.

PubMed

Hutchinson, K; Kerley, C; Cormican, L; Rochev, Y; Faul, J

2016-03-10

Since Vitamin D has anti-inflammatory effects we wondered whether the association between low serum 25OHD and airway obstruction in moderate persistent asthma might be explained by inflammatory pathways that worsen asthma. All subjects examined were Irish Caucasians with moderate persistent asthma and none took systemic steroid therapy. In addition to computerized spirometry, we measured BMI, serum 25-hydroxyvitamin D (25OHD), total IgE, Eosinophil Cationic Protein (ECP), and high sensitive C- reactive protein (hs-CRP). One hundred (47 male) subjects completed the testing. Within single level of asthma severity, 25OHD levels were related to post-bronchodilator FEV1/FVC (r = 0.26, p< 0.01), but multiple linear regression analysis demonstrated that the association was not explained by obesity or inflammatory markers. We find a relationship exists between airway obstruction and 25OHD levels in asthmatic adults, and the effect is not explained by the presence of potential confounders such as obesity, allergy and systemic inflammation.

Management of acute attacks of hereditary angioedema: potential role of icatibant.

PubMed

Longhurst, Hilary J

2010-09-07

Icatibant (Firazyr(®)) is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema.

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.

Assessing the independent contribution of maternal educational expectations to children's educational attainment in early adulthood: a propensity score matching analysis.

PubMed

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

2015-01-01

Parental educational expectations have been associated with children's educational attainment in a number of long-term longitudinal studies, but whether this relationship is causal has long been debated. The aims of this prospective study were twofold: 1) test whether low maternal educational expectations contributed to failure to graduate from high school; and 2) compare the results obtained using different strategies for accounting for confounding variables (i.e. multivariate regression and propensity score matching). The study sample included 1,279 participants from the Quebec Longitudinal Study of Kindergarten Children. Maternal educational expectations were assessed when the participants were aged 12 years. High school graduation—measuring educational attainment—was determined through the Quebec Ministry of Education when the participants were aged 22-23 years. Findings show that when using the most common statistical approach (i.e. multivariate regressions to adjust for a restricted set of potential confounders) the contribution of low maternal educational expectations to failure to graduate from high school was statistically significant. However, when using propensity score matching, the contribution of maternal expectations was reduced and remained statistically significant only for males. The results of this study are consistent with the possibility that the contribution of parental expectations to educational attainment is overestimated in the available literature. This may be explained by the use of a restricted range of potential confounding variables as well as the dearth of studies using appropriate statistical techniques and study designs in order to minimize confounding. Each of these techniques and designs, including propensity score matching, has its strengths and limitations: A more comprehensive understanding of the causal role of parental expectations will stem from a convergence of findings from studies using different techniques and designs.

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

PubMed

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

2017-08-24

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

A case study of nurse practitioner care compared to general practitioner care for children with respiratory tract infections.

PubMed

van Vugt, Saskia F; van de Pol, Alma C; Cleveringa, Frits G W; Stellato, Rebecca K; Kappers, Marieke P; de Wit, Niek J; Damoiseaux, Roger A M J

2018-05-13

To compare quality of care provided by nurse practitioners with care provided by general practitioners for children with respiratory tract infections in the Netherlands. Nurse practitioners increasingly manage acute conditions in general practice, with opportunities for more protocolled care. Studies on quality of nurse practitioners' care for children with respiratory tract infections are limited to the US health care system and do not take into account baseline differences in illness severity. Retrospective observational cohort study. Data were extracted from electronic healthcare records of children 0-6 years presenting with respiratory tract infection between January-December 2013. Primary outcomes were antibiotic prescriptions and early return visits. Generalized estimating equations were used to correct for potential confounders. A total of 899 respiratory tract infection consultations were assessed (168 seen by nurse practitioner; 731 by general practitioners). Baseline characteristics differed between these groups. Overall antibiotic prescription and early return visit rates were 21% and 24%, respectively. Adjusted odds ratio for antibiotic prescription after nurse practitioner vs. general practitioner delivered care was 1.40 (95% confidence interval 0.89-2.22) and for early return visits 1.53 (95% confidence interval 1.01-2.31). Important confounder for antibiotic prescription was illness severity. Presence of wheezing was a confounder for return visits. Complication and referral rates did not differ. Antibiotic prescription, complication and referral rates for paediatric respiratory tract infection consultations did not differ significantly between nurse practitioner and general practitioner consultations, after correction for potential confounders. General practitioners, however, see more severely ill children and have a lower return visit rate. A randomised controlled study is needed to determine whether nurse practitioner care quality is truly non-inferior. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

ERIC Educational Resources Information Center

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

2016-01-01

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

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

PubMed

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

2017-10-01

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

Association between Self-Reported Academic Performance and Risky Sexual Behavior among Ugandan University Students- A Cross Sectional Study

PubMed Central

Mehra, Devika; Kyagaba, Emmanuel; Östergren, Per-Olof; Agardh, Anette

2014-01-01

Little is known about the association between self-reported academic performance and risky sexual behaviors and if this differs by gender, among university students. Academic performance can create psychological pressure in young students. Poor academic performance might thus potentially contribute to risky sexual behavior among university students. The aim of this study was to investigate the association between self-reported academic performance and risky sexual behaviors, and whether gender affects this relationship among Ugandan university students. In 2010, 1,954 students participated in a cross-sectional survey, conducted at Mbarara University of Science and Technology in southwestern Uganda (72% response rate). Multivariate logistic regression analysis was used for the analysis. 1,179 (60.3%) students in our study sample reported having debuted sexually. Of these 440 (42.2%) used condoms inconsistently with new sexual partners, and 344 (33.6%) had had multiple sexual partners. We found a statistically significant association between poor academic performance and inconsistent condom use with a new sex partner and this association remained significant even after adjusting for all the potential confounders. There was no such association detected regarding multiple sexual partners. We also found that gender modified the effect of poor academic performance on inconsistent condom use. Females, who were poor academic performers, were found to be at a higher risk of inconsistent condom use than their male counterparts. Interventions should be designed to provide extra support to poor academic performers, which may improve their performance and self-esteem, which in turn might reduce their risky sexual behaviors. PMID:24999121

Association between self-reported academic performance and risky sexual behavior among Ugandan university students- a cross sectional study.

PubMed

Mehra, Devika; Kyagaba, Emmanuel; Ostergren, Per-Olof; Agardh, Anette

2014-04-16

Little is known about the association between self-reported academic performance and risky sexual behaviors and if this differs by gender, among university students. Academic performance can create psychological pressure in young students. Poor academic performance might thus potentially contribute to risky sexual behavior among university students. The aim of this study was to investigate the association between self-reported academic performance and risky sexual behaviors, and whether gender affects this relationship among Ugandan university students. In 2010, 1,954 students participated in a cross-sectional survey, conducted at Mbarara University of Science and Technology in southwestern Uganda (72% response rate). Multivariate logistic regression analysis was used for the analysis. 1,179 (60.3%) students in our study sample reported having debuted sexually. Of these 440 (42.2%) used condoms inconsistently with new sexual partners, and 344 (33.6%) had had multiple sexual partners. We found a statistically significant association between poor academic performance and inconsistent condom use with a new sex partner and this association remained significant even after adjusting for all the potential confounders. There was no such association detected regarding multiple sexual partners. We also found that gender modified the effect of poor academic performance on inconsistent condom use. Females, who were poor academic performers, were found to be at a higher risk of inconsistent condom use than their male counterparts. Interventions should be designed to provide extra support to poor academic performers, which may improve their performance and self-esteem, which in turn might reduce their risky sexual behaviors.

A case matched study examining the reliability of using ImPACT to assess effects of multiple concussions.

PubMed

Barker, Trevor; Russo, Stephen A; Barker, Gaytri; Rice, Mark A; Jeffrey, Mary G; Broderick, Gordon; Craddock, Travis J A

2017-04-28

Approximately 3.8 million sport and recreational concussions occur per year, creating a need for accurate diagnosis and management of concussions. Researchers and clinicians are exploring the potential dose-response cumulative effects of concussive injuries using computerized neuropsychological exams, however, results have been mixed and/or contradictory. This study starts with a large adolescent population and applies strict inclusion criteria to examine how previous mild traumatic brain injuries affect symptom reports and neurocognitive performance on the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) computerized tool. After applying exclusion criteria and case matching, 204 male and 99 female participants remained. These participants were grouped according to sex and the number of previous self-reported concussions and examined for overall differences on symptoms reported and scores obtained on the ImPACT neurocognitive battery composites. In an effort to further reduce confounding factors due to the varying group sizes, participants were then case matched on age, sex, and body mass index and analyzed for differences on symptoms reported and scores obtained on the ImPACT neurocognitive battery composites. Case matched analysis demonstrated males with concussions experience significantly higher rates of dizziness (p = .027, η 2  = .035), fogginess (p = .038, η 2  = .032), memory problems (p = .003, η 2  = .055), and concentration problems (p = .009, η 2  = .046) than males with no reported previous concussions. No significant effects were found for females, although females reporting two concussions demonstrated a slight trend for experiencing higher numbers of symptoms than females reporting no previous concussions. The results suggest that male adolescent athletes reporting multiple concussions have lingering concussive symptoms well after the last concussive event; however, these symptoms were found to be conflicting and better explained by complainer versus complacent attitudes in the population examined. Our results conflict with a significant portion of the current literature that uses relatively lenient inclusion and exclusion criteria, providing evidence of the importance of strict inclusion and exclusion criteria and examination of confounding factors when assessing the effects of concussions.

Instrumental variable methods in comparative safety and effectiveness research.

PubMed

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

2010-06-01

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

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.

Outcome modelling strategies in epidemiology: traditional methods and basic alternatives

PubMed Central

Greenland, Sander; Daniel, Rhian; Pearce, Neil

2016-01-01

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

Maternal obesity and childhood wheezing and asthma.

PubMed

Rusconi, Franca; Popovic, Maja

2017-03-01

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

Parent-based diagnosis of ADHD is as accurate as a teacher-based diagnosis of ADHD.

PubMed

Bied, Adam; Biederman, Joseph; Faraone, Stephen

2017-04-01

To review the literature evaluating the psychometric properties of parent and teacher informants relative to a gold-standard ADHD diagnosis in pediatric populations. We included studies that included both a parent and teacher informant, a gold-standard diagnosis, and diagnostic accuracy metrics. Potential confounds were evaluated. We also assessed the 'OR' and the 'AND' rules for combining informant reports. Eight articles met inclusion criteria. The diagnostic accuracy for predicting gold standard ADHD diagnoses did not differ between parents and teachers. Sample size, sample type, participant drop-out, participant age, participant gender, geographic area of the study, and date of study publication were assessed as potential confounds. Parent and teachers both yielded moderate to good diagnostic accuracy for ADHD diagnoses. Parent reports were statistically indistinguishable from those of teachers. The predictive features of the 'OR' and 'AND' rules are useful in evaluating approaches to better integrating information from these informants.

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/

Infrared Spectroscopic Imaging for Prostate Pathology Practice

DTIC Science & Technology

2011-04-01

features – geometric properties of epithelial cells/nuclei and lumens – that are quantified based on H&E stained images as well as FT-IR images of...the samples. By restricting the features used to geometric measures, we sought to mimic the pattern recognition process employed by human experts, and...relatively dark and can be modeled as small elliptical areas in the stained images. This geometrical model is often confounded as multiple nuclei can be

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

Resting-state FMRI confounds and cleanup

PubMed Central

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

2013-01-01

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

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.

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

PubMed

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

2016-09-10

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

Metabolic syndrome and shift work: a systematic review.

PubMed

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

2013-12-01

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

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

PubMed

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

2018-03-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2016-05-01

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

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

PubMed

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

2012-09-01

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

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-06-01

To examine how cannabis use and polysubstance use among cannabis users relate to psychosis spectrum (PS) symptoms in a large community-based sample of U.S. youth. Four thousand one hundred seventy-one youths (aged 14-21 years; mean = 16.90 years, SD = 1.85; 55% female) from the Philadelphia Neurodevelopmental Cohort completed assessments of substance use, PS symptoms, and confounding variables (e.g., demographics, comorbid psychopathology, and trauma exposure). After adjusting for confounds, cannabis use by itself was not associated with increased odds of being classified as "psychosis spectrum." However, cannabis use in combination with tobacco or other substance use was associated with increased odds of PS classification (adjusted odds ratios [ORs] = 1.37-1.76). Follow-up symptom-level analyses revealed that cannabis use in combination with other substances was associated with subclinical positive symptoms (ORs = 1.95 and 2.24) and frequent cannabis use was associated with subclinical negative/disorganized symptoms (OR = 2.14). However, these symptom-level findings were reduced to trends after correction for multiple comparisons. Neither cannabis use nor polysubstance use was associated with threshold delusions or hallucinations. After adjusting for important confounds, there was minimal evidence for associations between cannabis use by itself and PS symptoms. More compelling evidence emerged for associations between polysubstance use among cannabis users and PS symptoms. This study highlights the importance of considering polysubstance use and confounds when examining associations between cannabis use and PS symptoms. Further longitudinal research is necessary to determine whether these findings represent causal associations or shared genetic and/or environmental vulnerability for substance use and PS symptoms. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

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

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.

Early hematological and immunological alterations in gasoline station attendants exposed to benzene.

PubMed

Moro, Angela M; Brucker, Natália; Charão, Mariele F; Sauer, Elisa; Freitas, Fernando; Durgante, Juliano; Bubols, Guilherme; Campanharo, Sarah; Linden, Rafael; Souza, Ana P; Bonorino, Cristina; Moresco, Rafael; Pilger, Diogo; Gioda, Adriana; Farsky, Sandra; Duschl, Albert; Garcia, Solange C

2015-02-01

Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-01

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

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.

Early school attainment in late-preterm infants.

PubMed

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

2012-02-01

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

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

PubMed

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

2012-11-01

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

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

PubMed

Wong, O; Musselman, R P

1994-01-01

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

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

PubMed

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

2012-01-02

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

The protracted waste crisis and physical health of workers in Beirut: a comparative cross-sectional study.

PubMed

Morsi, Rami Z; Safa, Rawan; Baroud, Serge F; Fawaz, Cherine N; Farha, Jad I; El-Jardali, Fadi; Chaaya, Monique

2017-04-11

Since July 2015, Lebanon has been experiencing a waste management crisis. Dumpsites in inhabited areas and waste burning have emerged due to the waste accumulation, further adding to the gravity of the situation. However, the association between the crisis and health of the population has not been scientifically reported. A comparative cross-sectional study was conducted to assess whether exposure to open dumpsites and waste burning is associated with acute health symptoms. The study sample included 221 male workers between the ages of 18-60 years selected from two areas chosen based on their proximity to a garbage dumpsite and waste burning. 110 workers were exposed to a garbage dumpsite and waste burning, and 111 workers were not. Data were collected via a face-to-face interview using a newly developed validated structured questionnaire. Chi-square tests were used to check for statistically significant differences between exposure and covariates. Multivariable analyses using multiple logistic regression were used to compare health symptoms between exposed and unexposed workers adjusting for potential confounders. The prevalence of acute health symptoms was greater among the exposed workers than the non-exposed workers, including gastrointestinal, respiratory, dermatological and constitutional symptoms. Controlling for confounding variables, such as age, insurance, family support, residence near dumpsite, work site, and smoking, a minimum odds ratio (OR) of 4.30 was obtained when comparing the exposed population to those non-exposed. The strong association between improper waste management and physical health calls for immediate attention by the government, stakeholders and community members to find optimal solutions for this waste management crisis and set immediate priority interventions such as regular waste collection, volume reduction and recycling performance improvement. However, the long recall period may have underestimated our results.

Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations.

PubMed

Shrestha, Saurav; Hirvonen, Jussi; Hines, Christina S; Henter, Ioline D; Svenningsson, Per; Pike, Victor W; Innis, Robert B

2012-02-15

The serotonin-1A (5-HT(1A)) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT(1A) receptor density, two reported no change, and two reported increased 5-HT(1A) receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the 'gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter - like P-gp - at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT(1A) receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis. Published by Elsevier Inc.

Removal of restrictions following primary THA with posterolateral approach does not increase the risk of early dislocation.

PubMed

Gromov, Kirill; Troelsen, Anders; Otte, Kristian Stahl; Ørsnes, Thue; Ladelund, Steen; Husted, Henrik

2015-01-01

Patient education and mobilization restrictions are often used in an attempt to reduce the risk of dislocation following primary THA. To date, there have been no studies investigating the safety of removal of mobilization restrictions following THA performed using a posterolateral approach. In this retrospective non-inferiority study, we investigated the rate of early dislocation following primary THA in an unselected patient cohort before and after removal of postoperative mobilization restrictions. From the Danish National Health Registry, we identified patients with early dislocation in 2 consecutive and unselected cohorts of patients who received primary THA at our institution from 2004 through 2008 (n = 946) and from 2010 through 2014 (n = 1,329). Patients in the first cohort were mobilized with functional restrictions following primary THA whereas patients in the second cohort were allowed unrestricted mobilization. Risk of early dislocation (within 90 days) was compared in the 2 groups and odds ratio (OR)-adjusted for possible confounders-was calculated. Reasons for early dislocation in the 2 groups were identified. When we adjusted for potential confounders, we found no increased risk of early dislocation within 90 days in patients who were mobilized without restrictions. Risk of dislocation within 90 days was lower (3.4% vs 2.8%), risk of dislocation within 30 days was lower (2.1% vs 2.0%), and risk of multiple dislocations (1.8% vs 1.1%) was lower in patients who were mobilized without restrictions, but not statistically significantly so. Increasing age was an independent risk factor for dislocation. Removal of mobilization restrictions from the mobilization protocol following primary THA performed with a posterolateral approach did not lead to an increased risk of dislocation within 90 days.

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.

Sedentary Behavior and Mortality in Older Women

PubMed Central

Seguin, Rebecca; Buchner, David M.; Liu, Jingmin; Allison, Matthew; Manini, Todd; Wang, Ching-Yun; Manson, JoAnn E.; Messina, Catherine R.; Patel, Mahesh J.; Moreland, Larry; Stefanick, Marcia L.; LaCroix, Andrea Z.

2013-01-01

Background Although epidemiologic studies have shown associations between sedentary behavior and mortality, few have focused on older women with adequate minority representation and few have controlled for both physical activity and functional status. Purpose The objective of this study was to determine the relationship between sedentary time and total; cardiovascular disease (CVD); coronary heart disease (CHD); and cancer mortality in a prospective, multiethnic cohort of postmenopausal women. Methods The study population included 92,234 women aged 50–79 years at baseline (1993–1998) who participated in the Women’s Health Initiative Observational Study through September 2010. Self-reported sedentary time was assessed by questionnaire and examined in 4 categories (≤4, >4–8, ≥8–11, >11 hours). Mortality risks were examined using Cox proportional hazard models adjusting for confounders. Models were also stratified by age, race/ethnicity, body mass index, physical activity, physical function, and chronic disease to examine possible effect modification. Analyses were conducted in 2012–2013. Results The mean follow-up period was 12 years. Compared with women who reported the least sedentary time, women reporting the highest sedentary time had increased risk of all-cause mortality in the multivariate model (HR=1.12, 95% CI=1.05, 1.21). Results comparing the highest versus lowest categories for CVD, CHD, and cancer mortality were as follows: HR=1.13, 95% CI=0.99, 1.29; HR=1.27, 95% CI=1.04, 1.55; and HR=1.21, 95% CI=1.07, 1.37, respectively. For all mortality outcomes, there were significant linear tests for trend. Conclusions There was a linear relationship between greater amounts of sedentary time and mortality risk after controlling for multiple potential confounders. PMID:24439345

Pregnancy context and women's health-related quality of life.

PubMed

Gariepy, Aileen; Lundsberg, Lisbet S; Vilardo, Nicole; Stanwood, Nancy; Yonkers, Kimberly; Schwarz, Eleanor B

2017-05-01

The objective was to quantify the association of pregnancy context and health-related quality of life (HRQoL). English- or Spanish-speaking women, aged 16-44, with pregnancies <24 weeks' gestation were enrolled in this cross-sectional study between June 2014 and June 2015. Participants completed self-assessments of pregnancy "context," including timing, intention, wantedness, desirability, happiness, and planning (measured with the London Measure of Unplanned Pregnancy). HRQoL was measured using the Patient Reported Outcomes Measurement Information System Global Short Form. Associations between measures of pregnancy context and HRQoL scores in the lowest tertile were examined using multivariable logistic regression to adjust for potential confounding variables. We enrolled 161 participants (mean age=27.2±6.6 years). Only 14% self-identified as White, non-Hispanic; 42% Hispanic; 37% Black, non-Hispanic; and 7% multiracial. Most (79%) participants were unmarried, and 75% were parenting. Mean gestational age was 9±4.6 weeks. In unadjusted models, women reporting mixed feelings about wanting to have a baby, an undesired pregnancy or feeling unhappy about learning of their pregnancy more frequently had low mental and physical HRQoL compared to women reporting wanted, desired, happy pregnancies. Women with an unplanned pregnancy or pregnancy occurring at the wrong time also had lower physical HRQoL than women reporting pregnancies that were planned or happened at the right time. However, after multivariate adjustment, including history of depression, pregnancy contexts were not associated with low mental or physical HRQoL. After adjusting for multiple confounders, pregnancy context is not significantly associated with HRQoL. The focus on pregnancy intention in public health programs may not sufficiently assess multidimensional aspects of pregnancy context and may not align with patient-centered outcomes such as HRQoL. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between differential gene expression and body mass index among endometrial cancers from The Cancer Genome Atlas Project.

PubMed

Roque, Dario R; Makowski, Liza; Chen, Ting-Huei; Rashid, Naim; Hayes, D Neil; Bae-Jump, Victoria

2016-08-01

The Cancer Genome Atlas (TCGA) identified four integrated clusters for endometrial cancer (EC): POLE, MSI, CNL and CNH. We evaluated differences in gene expression profiles of obese and non-obese women with EC and examined the association of body mass index (BMI) within the clusters identified in TCGA. TCGA RNAseq data was used to identify genes related to increasing BMI among ECs. The POLE, MSI and CNL clusters were composed mostly of endometrioid EC. Patient BMI was compared between these three clusters with one-way ANOVA. Association between gene expression and BMI was also assessed while adjusting for confounding effects of potential confounding factors. p-Values testing the association between gene expression and BMI were adjusted for multiple hypothesis testing over the 20,531 genes considered. Mean BMI was statistically different between the ECs in the CNL (35.8) versus POLE (29.8) cluster (p=0.006) and approached significance for the MSI (33.0) versus CNL (35.8) cluster (p=0.05). 181 genes were significantly up- or down-regulated with increasing BMI in endometrioid EC (q-value<0.01), including LPL, IRS-1, IGFBP4, IGFBP7 and the progesterone receptor. DAVID functional annotation analysis revealed significant enrichment in "cell cycle" (adjusted p-value=1.5E-5) and "DNA metabolic processes" (adjusted p-value=1E-3) for the identified genes. Obesity related genes were found to be upregulated with increasing BMI among endometrioid ECs. Patients with POLE tumors have the lowest median BMI when compared to MSI and CNL. Given the heterogeneity among endometrioid EC, consideration should be given to abandoning the Type I and II classification of EC tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Short Berg Balance Scale, BBS-9, as a predictor of fall risk among the aged: a prospective 12-month follow-up study.

PubMed

Hohtari-Kivimäki, Ulla; Salminen, Marika; Vahlberg, Tero; Kivelä, Sirkka-Liisa

2013-12-01

The aim of this study was to assess the adequacy of the short, 9-item Berg Balance Scale (BBS-9) to predict fall risk among the community-dwelling aged. The subjects (n = 519) were derived from the participants in a multifactorial fall prevention intervention conducted in Pori, Finland. Receiver operating characteristic (ROC) analysis was used to determine the cut-off score for BBS-9 (range 0-36) to classify aged people with a fall risk during a 12-month follow-up. Logistic regression was used to analyse the relationship of potential confounders with fall risk. The association between the cut-off score for BBS-9 and fall risk was tested using the Chi-square test. In determining the cut-off score of BBS-9 to classify fall risk, the highest sensitivity (0.51) and specificity (0.57) (when both presumed to be above 0.50) sum score was within the limit range 32 scores or below. The area under curve (AUC) was significantly better in the model adjusted for significant confounders (vision and the number of regularly used drugs) (AUC = 0.64) than in the unadjusted model (AUC = 0.57) (p = 0.045). Among patients who scored 32 or below in BBS-9 the incidence of multiple falls was 20.0 %, whereas among those who scored 33-36 it was 15.7 %. BBS-9 with the cut-off score of 32/33 together with data on vision and the number of regularly used drugs predicted moderately the risk of falling among the community-dwelling aged.

Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of obesity and hypoxia.

PubMed

Stanke-Labesque, Françoise; Bäck, Magnus; Lefebvre, Blandine; Tamisier, Renaud; Baguet, Jean-Philippe; Arnol, Nathalie; Lévy, Patrick; Pépin, Jean-Louis

2009-08-01

Low-grade inflammation may potentially explain the relationship between obstructive sleep apnea syndrome (OSA) and cardiovascular events. However, the respective contribution of intermittent hypoxia and confounders, such as obesity, is still debated. To monitor urinary leukotriene E(4) (U-LTE(4)), a validated marker of proinflammatory cysteinyl leukotriene production, in OSA; to determine the influence of obesity and other confounders on U-LTE(4) concentrations; to examine the mechanisms involved through transcriptional profiling of the leukotriene pathway in peripheral blood mononuclear cells (PBMCs); and to investigate the effect of continuous positive air pressure (CPAP) on U-LTE(4) concentrations. We measured U-LTE(4) by liquid chromatography-tandem mass spectrometry. The U-LTE(4) concentrations were increased (P = .019) in 40 nonobese patients with OSA carefully matched for age, sex, and body mass index (BMI) to 25 control subjects, and correlated (r = 0.0312; P = .017) to the percentage of time spent with mean oxygen saturation (SaO(2)) less than 90%. In a larger cohort of patients with OSA (n = 72), U-LTE(4) increased as a function of BMI (r = 0.445; P = .0002). In those patients, the expression levels of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited a similar pattern. A stepwise multiple linear regression analysis performed in this cohort identified BMI (P = .001; regression coefficient, 3.33) and percentage of time spent with SaO(2) <90% (P = .001; regression coefficient, 1.01) as independent predictors of U-LTE(4) concentrations. Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4) concentrations only in patients with OSA with normal BMI. Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA.

Can early introduction of egg prevent egg allergy in infants? A population-based study.

PubMed

Koplin, Jennifer J; Osborne, Nicholas J; Wake, Melissa; Martin, Pamela E; Gurrin, Lyle C; Robinson, Marnie N; Tey, Dean; Slaa, Marjolein; Thiele, Leone; Miles, Lucy; Anderson, Deborah; Tan, Tina; Dang, Thanh D; Hill, David J; Lowe, Adrian J; Matheson, Melanie C; Ponsonby, Anne-Louise; Tang, Mimi L K; Dharmage, Shyamali C; Allen, Katrina J

2010-10-01

Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Is Healthier Nutrition Behaviour Associated with Better Self-Reported Health and Less Health Complaints? Evidence from Turku, Finland

PubMed Central

El Ansari, Walid; Suominen, Sakari; Berg-Beckhoff, Gabriele

2015-01-01

We examined nutrition behaviour, self-reported health and 20 health complaints of undergraduates in Finland. Students at the University of Turku in Finland participated in a cross-sectional online survey (N = 1189). For nutrition behaviour, we computed two composite food intake pattern scores (sweets, cakes and snacks; and fruits and vegetables), a dietary guideline adherence index and the subjective importance of healthy eating. Multinomial logistic regression assessed the association of students’ nutrition behaviour with three levels of self-reported health, controlling for many potential confounders (age, sex, living with partner, economic situation, moderate physical activity, Faculty and BMI). Factor analysis of the 20 health complaints revealed three components (psychological, pains/aches and circulatory/breathing symptoms). Multiple linear regression tested the association of students’ eating habits with the three components of health complaints, controlling for the same confounders. Fruits and raw and cooked vegetable consumption, dietary guideline adherence index and subjective importance of healthy eating were highest among students with excellent/very good self-reported health, exhibiting a decreasing trend for those individuals with poor/fair self-reported health. High levels of psychological symptoms were associated with decreased consumption of fruits and vegetables, less dietary guideline adherence and less subjective importance of healthy eating. Pain/aches symptoms were associated with a higher consumption of sweets, cookies and snacks and a lower adherence to dietary guidelines. More healthy nutrition behaviour was consistently associated with better self-reported health and less health complaints. Of the four nutrition behaviour indicators we employed, the dietary guideline adherence index was the best indicator and exhibited the most consistent associations with self-reported health and health complaints. PMID:26473918

Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations

PubMed Central

Shrestha, Saurav; Hirvonen, Jussi; Hines, Christina S.; Henter, Ioline; Svenningsson, Per; Pike, Victor W.; Innis, Robert B.

2011-01-01

The serotonin-1A (5-HT1A) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT1A receptor density, two reported no change, and two reported increased 5-HT1A receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the `gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter—like P-gp—at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT1A receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis. PMID:22155042

Characteristics of care management agencies affect expenditure on home help and day care services: A population-based cross-sectional study in Japan.

PubMed

Feng, Mei; Igarashi, Ayumi; Noguchi-Watanabe, Maiko; Yoshie, Satoru; Iijima, Katsuya; Yamamoto-Mitani, Noriko

2017-11-01

The financial interests of care management agencies can affect how care managers assist clients' use of long-term care insurance services. The present study examined the relationship between clients' service expenditures, and whether the home help and day care service agencies belonged to the same organization as the care management agency. Population-based data were obtained from a suburban municipality in Japan. We investigated 4331 persons with care needs certificates (levels 1-5), including those using home help (n = 1780) or day care (n = 2141) services. Data on the service expenditures, and clients' and agencies' characteristics were analyzed using multiple linear regression analyses controlling for potential confounders. Home help service users spent an average of US$558.1 ± 590.1 for home help service, and day care service users spent US$665.0 ± 415.9 for day care service. Living alone, living in a condominium/apartment, higher care needs, more severe cognitive impairment and lower use of other services were associated with higher home help service expenditure. Day care service expenditure increased with older age, female sex, higher care needs, more severe cognitive impairment and higher physical function. Clients whose service agencies and care management agencies belonged to the same organization had higher expenditures, even after adjusting for confounders (home help: β = 0.126, P = 0.007; day care: β = 0.085, P = 0.002, respectively). Financial interests of care management agencies might significantly influence clients' service expenditure. We should develop an effective system to minimize this influence. Geriatr Gerontol Int 2017; 17: 2224-2231. © 2017 Japan Geriatrics Society.

Can we predict urinary stress incontinence by using demographic, clinical, imaging and urodynamic data?

PubMed

Wlaźlak, Edyta; Surkont, Grzegorz; Shek, Ka L; Dietz, Hans P

2015-10-01

It has been claimed that urethral hypermobility and resting urethral pressure can largely explain stress incontinence in women. In this study we tried to replicate these findings in an unselected cohort of women seen for urodynamic testing, including as many potential confounders as possible. This study is a retrospective analysis of data obtained from 341 women. They attended for urodynamic testing due to symptoms of pelvic floor dysfunction. We excluded from the analysis women with a history of previous anti-incontinence and prolapse surgery. All patients had a standardised clinical assessment, 4D transperineal pelvic floor ultrasound and multichannel urodynamic testing. Urodynamic stress incontinence (USI) was diagnosed by multichannel urodynamic testing. Its severity was subjectively graded as mild, moderate and severe. Candidate variables were: age, BMI, symptoms of prolapse, vaginal parity, significant prolapse (compartment-specific), levator avulsion, levator hiatal area, Oxford grading, midurethral mobility, maximum urethral pressure (MUP), maximum cough pressure and maximum Valsalva pressure reached. On binary logistic regression, the following parameters were statistically significant in predicting urodynamic stress incontinence: age (P=0.03), significant rectocele (P=0.02), max. abdominal pressure reached (negatively, P<0.0001), midurethral mobility (P=0.0004) and MUP (negatively, P<0.0001). On multivariate analysis, accounting for multiple interdependencies, the following predictors remained significant: max. abdominal pressure reached (negatively, P<0.0001), cough pressure (P=0.006), midurethral mobility (P=0.003) and MUP (negatively, P<0.0001), giving an R(2) of 0.24. Mid-urethral mobility and MUP are the main predictors of USI. Demographic and clinical data are at best weak predictors. Our results suggest the presence of major unrecognised confounders. Copyright © 2015. Published by Elsevier Ireland Ltd.

Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function

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

Ohno, Tomoko; Sakamoto, Mineshi; Kurosawa, Tomoko

2007-02-15

To investigate the relations among total mercury levels in hair, toenail, and urine, together with potential effects of methylmercury intake on renal tubular function, we determined their levels, and urinary N-acetyl-{beta}-d-glucosaminidase activity (NAG) and {alpha}{sub 1}-microglobulin (AMG) in 59 women free from occupational exposures, and estimated daily mercury intakes from fish and other seafood using a food frequency questionnaire. Mercury levels (mean+/-SD) in the women were 1.51+/-0.91{mu}g/g in hair, 0.59+/-0.32{mu}g/g in toenail, and 0.86+/-0.66{mu}g/g creatinine in urine; and, there were positive correlations among them (P<0.001). The daily mercury intake of 9.15+/-7.84{mu}g/day was significantly correlated with total mercury levels in hair,more » toenail, and urine (r=0.551, 0.537, and 0.604, P<0.001). Among the women, the NAG and AMG were positively correlated with both the daily mercury intake and mercury levels in hair, toenail, and urine (P<0.01); and, these relations were almost similar when using multiple regression analysis to adjust for possible confounders such as urinary cadmium (0.47+/-0.28{mu}g/g creatinine) and smoking status. In conclusion, mercury resulting from fish consumption can explain total mercury levels in hair, toenail, and urine to some degree (about 30%), partly through the degradation into the inorganic form, and it may confound the renal tubular effect of other nephrotoxic agents. Also, the following equation may be applicable to the population neither with dental amalgam fillings nor with occupational exposures: [hair mercury ({mu}g/g)]=2.44x[toenail mercury ({mu}g/g)].« less

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.

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

PubMed

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

2014-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

The effect of single and multiple infections on atopy and wheezing in children

PubMed Central

Alcantara-Neves, Neuza Maria; Veiga, Rafael Valente; Dattoli, Vitor Camilo Cavalcante; Fiaccone, Rosimeire Leovigildo; Esquivel, Renata; Cruz, Álvaro Augusto; Cooper, Philip John; Rodrigues, Laura Cunha; Barreto, Maurício Lima

2016-01-01

Background The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. Objective We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. Methods Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. Results Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. Conclusion The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms. PMID:22035877

Is social isolation/alienation confounded with, and non-independent of, emotional distress in its association with early onset of coronary artery disease?

PubMed

Ketterer, Mark; Rose, Benjamin; Knysz, Walter; Farha, Amjad; Deveshwar, Sangita; Schairer, John; Keteyian, Steven J

2011-03-01

Both emotional distress (ED) and social isolation/alienation (SI/A) have been found to prospectively predict adverse cardiac events, but few studies have tested the confounding/redundancy of these measures as correlates/predictors of outcomes. In this study, 163 patients with documented coronary artery disease (CAD) were interviewed for multiple indices of SI/A and administered the Symptom Checklist 90 - Revised (SCL90R). A spouse or friend provided an independent rating of ED using the spouse/friend version of the Ketterer Stress Symptom Frequency Checklist (KSSFC). The measures of ED and SI/A covaried. All three scales from the KSSFC (depression, anxiety, and "AIAI" - aggravation, irritation, anger, and impatience), and three scales from the SCL90R (anxiety, depression, and psychoticism), were associated with early Age at Initial Diagnosis (AAID) of CAD. Neither three scales derived from the SCL90R (shyness, feeling abused, and feeling lonely) nor the interview indices of SI/A (married, living alone, having a confidant, self description as a lone wolf, and self-description as lonely) were associated with early AAID. Thus, it is concluded that the present results indicate that ED and SI/A are confounded and that, even when tested head-to-head in a multivariate analysis, only ED is associated with AAID.

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

PubMed Central

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

2010-01-01

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

Estimating influenza vaccine effectiveness: Evolution of methods to better understand effects of confounding in older adults.

PubMed

McElhaney, Janet E; Andrew, Melissa K; McNeil, Shelly A

2017-11-01

Older adults are at high risk for serious complications of influenza illness and loss of vaccine-mediated protection. It is increasingly recognized that in addition to age, multiple chronic conditions and associated frailty contribute to the decline in vaccine effectiveness in this population. However, observational studies have been fraught with issues of confounding related to the degree of frailty and functional decline, measures of which are not included in standard administrative health care databases that are used to calculate vaccine effectiveness. This issue has led to the identification of confounding by indication or from "healthy vaccinee" bias, which respectively lead to underestimates or overestimates of influenza vaccine effectiveness. In addition, the sensitivity and specificity of the criteria used to define influenza-like illness declines with increasing age due to atypical presentations of illness and the inability to distinguish between influenza and other respiratory viruses. The test-negative case:control design has emerged as a method to estimate influenza vaccine effectiveness by comparing vaccination rates in those with laboratory-confirmed influenza to those with other acute viral respiratory illnesses. This review provides a perspective on how test-negative case:control study designs and new insights into mechanisms of protection have considerably strengthened influenza vaccination policy decisions for older adults that have historically been undermined by the conclusions of observational studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue.

PubMed

Rosalie Driehuis, Emma; van den Akker, Lizanne Eva; de Groot, Vincent; Beckerman, Heleen

2018-02-13

To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. A cross-sectional study. Sixty-two participants with multiple sclerosis-related fatigue. Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min). Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), physical functioning with the Short Form 36 - physical functioning (SF36-pf), and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA). Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status). Mean maximal oxygen uptake (VO2max) was 23.9 ml/kg/min (standard deviation (SD) 6.3 ml/kg/min). There was no significant relationship between VO2max and physical activity (PASIPD): β = 0.320, 95% confidence interval (95% CI) = -0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf): β = 1.527, 95% CI = 0.820-2.234, R2 = 25.9%, and was significantly related to IPA domains "autonomy indoors" (β = -0.043, 95% CI = -0.067 to -0.020, R2 = 20.6%), "autonomy outdoors" (β = -0.037, 95% CI = -0.062 to -0.012, R2 = 18.2%) and "social life and relationships" (β=-0.033, 95% CI = -0.060 to -0.007, R2 = 21.3%). Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

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

PubMed

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

2012-06-01

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

Analyzing the Impacts of Dams on Riparian Ecosystems: A Review of Research Strategies and Their Relevance to the Snake River Through Hells Canyon

PubMed Central

Braatne, Jeffrey H.; Goater, Lori A.; Blair, Charles L.

2007-01-01

River damming provides a dominant human impact on river environments worldwide, and while local impacts of reservoir flooding are immediate, subsequent ecological impacts downstream can be extensive. In this article, we assess seven research strategies for analyzing the impacts of dams and river flow regulation on riparian ecosystems. These include spatial comparisons of (1) upstream versus downstream reaches, (2) progressive downstream patterns, or (3) the dammed river versus an adjacent free-flowing or differently regulated river(s). Temporal comparisons consider (4) pre- versus post-dam, or (5) sequential post-dam conditions. However, spatial comparisons are complicated by the fact that dams are not randomly located, and temporal comparisons are commonly limited by sparse historic information. As a result, comparative approaches are often correlative and vulnerable to confounding factors. To complement these analyses, (6) flow or sediment modifications can be implemented to test causal associations. Finally, (7) process-based modeling represents a predictive approach incorporating hydrogeomorphic processes and their biological consequences. In a case study of Hells Canyon, the upstream versus downstream comparison is confounded by a dramatic geomorphic transition. Comparison of the multiple reaches below the dams should be useful, and the comparison of Snake River with the adjacent free-flowing Salmon River may provide the strongest spatial comparison. A pre- versus post-dam comparison would provide the most direct study approach, but pre-dam information is limited to historic reports and archival photographs. We conclude that multiple study approaches are essential to provide confident interpretations of ecological impacts downstream from dams, and propose a comprehensive study for Hells Canyon that integrates multiple research strategies. PMID:18043964

Association of Lifestyle-Related Comorbidities With Periodontitis

PubMed Central

Lee, Jae-Hong; Lee, Jung-Seok; Park, Jin-Young; Choi, Jung-Kyu; Kim, Dong-Wook; Kim, Young-Taek; Choi, Seong-Ho

2015-01-01

Abstract The aim of this study was to determine the association of periodontitis with lifestyle-related comorbidities (LCs) using data in the Korean National Health Insurance Cohort Database from 2002 to 2013. This was a retrospective study involving a large national cohort with patient samples (representing 2% of the total Korean population) stratified on the basis of sociodemographic information. Using this precisely extracted database, the correlations between LCs (cerebral infarction, angina pectoris, myocardial infarction, hypertension, diabetes mellitus, rheumatoid arthritis, erectile dysfunction, osteoporosis, and obesity) and periodontitis were investigated while adjusting for confounding bias. Univariate and multiple logistic regression analyses were used to evaluate differences in variable factors. Among a total of 1,025,340 samples, 321,103 (31.3%) cases were diagnosed with periodontitis. Statistically significant associations were found between all LCs except myocardial infarction and periodontitis (P < 0.005). Periodontitis is significantly and positively correlated with LCs (except for myocardial infarction) after adjusting for confounding bias. In particular, lifestyle-related diseases, erectile dysfunction, and osteoporosis seem to be intimately related to periodontitis. PMID:26376407

Pet Ownership and Cancer Risk in the Women's Health Initiative.

PubMed

Garcia, David O; Lander, Eric M; Wertheim, Betsy C; Manson, JoAnn E; Volpe, Stella L; Chlebowski, Rowan T; Stefanick, Marcia L; Lessin, Lawrence S; Kuller, Lewis H; Thomson, Cynthia A

2016-09-01

Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders. There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Pet ownership had no association with overall cancer incidence. This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311-6. ©2016 AACR. ©2016 American Association for Cancer Research.

The Impact of State Preemption of Local Smoking Restrictions on Public Health Protections and Changes in Social Norms

PubMed Central

Mowery, Paul D.; Babb, Steve; Hobart, Robin; Tworek, Cindy; MacNeil, Allison

2012-01-01

Introduction. Preemption is a legislative or judicial arrangement in which a higher level of government precludes lower levels of government from exercising authority over a topic. In the area of smoke-free policy, preemption typically takes the form of a state law that prevents communities from adopting local smoking restrictions. Background. A broad consensus exists among tobacco control practitioners that preemption adversely impacts tobacco control efforts. This paper examines the effect of state provisions preempting local smoking restrictions in enclosed public places and workplaces. Methods. Multiple data sources were used to assess the impact of state preemptive laws on the proportion of indoor workers covered by smoke-free workplace policies and public support for smoke-free policies. We controlled for potential confounding variables. Results. State preemptive laws were associated with fewer local ordinances restricting smoking, a reduced level of worker protection from secondhand smoke, and reduced support for smoke-free policies among current smokers. Discussion. State preemptive laws have several effects that could impede progress in secondhand smoke protections and broader tobacco control efforts. Conclusion. Practitioners and advocates working on other public health issues should familiarize themselves with the benefits of local policy making and the potential impact of preemption. PMID:22654921

Sleep in lonely heroin-dependent patients receiving methadone maintenance treatment: longer sleep latency, shorter sleep duration, lower sleep efficiency, and poorer sleep quality.

PubMed

Li, Hong-Jie; Zhong, Bao-Liang; Xu, Yan-Min; Zhu, Jun-Hong; Lu, Jin

2017-10-24

Given the socially isolated status of Chinese heroin-dependent patients (HDPs) and the significant association between loneliness and sleep problem in the general population, the impact of loneliness on sleep of HDPs is potentially substantial. The study aimed to test whether loneliness is associated with poor sleep in terms of quantity and quality in a consecutive sample of Chinese HDPs receiving methadone maintenance treatment (MMT). The study participants were 603 HDPs of three MMT clinics in Wuhan, China. Data on socio-demographic and clinical characteristics were collected by a standardized self-administered questionnaire. Sleep outcomes included sleep latency, sleep duration, sleep efficiency, and sleep quality. We measured depressive symptoms, loneliness, and sleep quality by using Zung's Self-rating Depression Scale, the single-item self-report of loneliness, and the Pittsburgh Sleep Quality Index, respectively. Multiple linear regression was used to examine whether loneliness is independently associated with sleep measures. After controlling for the confounding effects of potential socio-demographic and clinical variables, loneliness was significantly associated with longer sleep latency, shorter sleep duration, lower sleep efficiency, and poorer sleep quality. Loneliness may exacerbate sleep disturbance in Chinese HDPs of MMT clinics. Psychosocial interventions aimed at reducing loneliness in MMT clinics would improve the sleep of HDPs.

Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study.

PubMed

Morinaga, Jun; Zhao, Jiabin; Endo, Motoyoshi; Kadomatsu, Tsuyoshi; Miyata, Keishi; Sugizaki, Taichi; Okadome, Yusuke; Tian, Zhe; Horiguchi, Haruki; Miyashita, Kazuya; Maruyama, Nobuhiro; Mukoyama, Masashi; Oike, Yuichi

2018-01-01

Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation. Circulating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels. Circulating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development.

Relationship between metabolic syndrome and moderate-to-vigorous physical activity in youth.

PubMed

Machado-Rodrigues, Aristides M; Leite, Neiva; Coelho e Silva, Manuel J; Valente-dos-Santos, João; Martins, Raul A; Mascarenhas, Luis P G; Boguszewski, Margaret C S; Padez, Cristina; Malina, Robert M

2015-01-01

Associations of metabolic syndrome (MetS) with lifestyle behaviors in youth is potentially important for identifying subgroups at risk and encourage interventions. This study evaluates the associations among the clustering of metabolic risk factors and moderate-to-vigorous physical activity (MVPA) in youth. The sample comprised 522 girls and 402 boys (N = 924) aged 11 to 17 years. Height, weight, waist circumference (WC), fasting glucose, high-density lipoprotein cholesterol, triglycerides, and blood pressures were measured. Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test. MVPA was estimated with a 3-day diary. Outcome variables were statistically normalized and expressed as z scores. A clustered metabolic risk score was computed as the mean of z scores. Multiple linear regression was used to test associations between metabolic risk and MVPA by sex, adjusted for age, WC, and CRF. After adjustment for potential confounders, MVPA was inversely associated with the clustering of metabolic risk factors in girls, but not in boys; in addition, after adjusting for WC, the statistical model of that relationship was substantially improved in girls. MVPA was independently associated with increased risk of MetS in girls. Additional efforts are needed to encourage research with different analytical approach and standardization of criteria for MetS in youth.

The Shared Pathoetiological Effects of Particulate Air Pollution and the Social Environment on Fetal-Placental Development

PubMed Central

2014-01-01

Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these mechanisms intersect with those related to socioeconomic status. Here we review the role of oxidative stress, inflammation and endocrine modification in the pathoetiology of deficient deep placentation and detail how the physical and social environments can act alone and collectively to mediate the established pathology linked to a spectrum of adverse pregnancy outcomes. We review the experimental and epidemiological literature showing that diet/nutrition, smoking, and psychosocial stress share similar pathways with that of particulate air pollution exposure to potentially exasperate the negative effects of either insult alone. Therefore, socially patterned risk factors often treated as nuisance parameters should be explored as potential effect modifiers that may operate at multiple levels of social geography. The degree to which deleterious exposures can be ameliorated or exacerbated via community-level social and environmental characteristics needs further exploration. PMID:25574176

The case for causal influences of action videogame play upon vision and attention.

PubMed

Kristjánsson, Árni

2013-05-01

Over the past decade, exciting findings have surfaced suggesting that routine action videogame play improves attentional and perceptual skills. Apparently, performance during multiple-object tracking, useful-field-of-view tests, and task switching improves, contrast sensitivity and spatial-resolution thresholds decrease, and the attentional blink and backward masking are lessened by short-term training on action videogames. These are remarkable findings showing promise for the training of attention and the treatment of disorders of attentional function. While the findings are interesting, evidence of causal influences of videogame play is not as strong as is often claimed. In many studies, observers with game play experience and those without are tested. Such studies do not address causality, since preexisting differences are not controlled for. Other studies investigate the training of videogame play, with some evidence of training benefits. Methodological shortcomings and potential confounds limit their impact, however, and they have not always been replicated. No longitudinal studies on videogame training exist, but these may be required to provide conclusive answers about any benefits of videogame training and any interaction with preexisting differences. Suggestions for methodological improvement are made here, including recommendations for longitudinal studies. Such studies may become crucial for the field of attentional training to reach its full potential.

Pet Ownership and Cancer Risk in the Women’s Health Initiative

PubMed Central

Garcia, David O.; Lander, Eric M.; Wertheim, Betsy C.; Manson, JoAnn E.; Volpe, Stella L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Lessin, Lawrence S.; Kuller, Lewis H.; Thomson, Cynthia A.

2016-01-01

Background Pet ownership and cancer are both highly prevalent in the U.S. Evidence suggest associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. Methods A prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women’s Health Initiative (WHI) observational study and clinical trials. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between pet ownership and cancer, adjusted for potential confounders. Results There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Conclusion Pet ownership had no association with overall cancer incidence. Impact This is the first large epidemiological study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. PMID:27365150

Mechanism-Based Urinary Biomarkers to Identify the Potential for Aminoglycoside-Induced Nephrotoxicity in Premature Neonates: A Proof-of-Concept Study

PubMed Central

Sabbisetti, Venkata; Turner, Mark A.; Farragher, Tracey; Bonventre, Joseph V.; Park, B. Kevin; Smyth, Rosalind L.; Pirmohamed, Munir

2012-01-01

Premature infants are frequently exposed to aminoglycoside antibiotics. Novel urinary biomarkers may provide a non-invasive means for the early identification of aminoglycoside-related proximal tubule renal toxicity, to enable adjustment of treatment and identification of infants at risk of long-term renal impairment. In this proof-of-concept study, urine samples were collected from 41 premature neonates (≤32 weeks gestation) at least once per week, and daily during courses of gentamicin, and for 3 days afterwards. Significant increases were observed in the three urinary biomarkers measured (Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG)) during treatment with multiple courses of gentamicin. When adjusted for potential confounders, the treatment effect of gentamicin remained significant only for KIM-1 (mean difference from not treated, 1.35 ng/mg urinary creatinine; 95% CI 0.05–2.65). Our study shows that (a) it is possible to collect serial urine samples from premature neonates, and that (b) proximal tubule specific urinary biomarkers can act as indicators of aminoglycoside-associated nephrotoxicity in this age group. Further studies to investigate the clinical utility of novel urinary biomarkers in comparison to serum creatinine need to be undertaken. PMID:22937100

Relation of serum γ-glutamyl transferase activity with copper in an adult population.

PubMed

Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

2017-10-26

The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, p<0.001). There was a positive correlation between serum γ-GGT activity and copper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, p<0.001; r=0.230, p=0.010). The results of multiple linear regression analysis showed that serum γ-GGT maintained a significantly positive correlation with copper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

The association between subgingival periodontal pathogens and systemic inflammation.

PubMed

Winning, Lewis; Patterson, Christopher C; Cullen, Kathy M; Stevenson, Kathryn A; Lundy, Fionnuala T; Kee, Frank; Linden, Gerard J

2015-09-01

To investigate associations between periodontal disease pathogens and levels of systemic inflammation measured by C-reactive protein (CRP). A representative sample of dentate 60-70-year-old men in Northern Ireland had a comprehensive periodontal examination. Men taking statins were excluded. Subgingival plaque samples were analysed by quantitative real time PCR to identify the presence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia. High-sensitivity CRP (mg/l) was measured from fasting blood samples. Multiple linear regression analysis was performed using log-transformed CRP concentration as the dependent variable, with the presence of each periodontal pathogen as predictor variables, with adjustment for various potential confounders. A total of 518 men (mean age 63.6 SD 3.0 years) were included in the analysis. Multiple regression analysis showed that body mass index (p < 0.001), current smoking (p < 0.01), the detectable presence of P. gingivalis (p < 0.01) and hypertension (p = 0.01), were independently associated with an increased CRP. The detectable presence of P. gingivalis was associated with a 20% (95% confidence interval 4-35%) increase in CRP (mg/l) after adjustment for all other predictor variables. In these 60-70-year-old dentate men, the presence of P. gingivalis in subgingival plaque was significantly associated with a raised level of C-reactive protein. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does Neostigmine Administration Produce a Clinically Important Increase in Postoperative Nausea and Vomiting?

PubMed Central

Cheng, Ching-Rong; Sessler, Daniel I.; Apfel, Christian C.

2005-01-01

Neostigmine is used to antagonize neoromuscluar blocker-induced residual neuromuscular paralysis. Despite a previous meta-analysis, the effect of neostigmine on postoperative nausea and vomiting (PONV) remains unresolved. We reevaluated the effect of neostigmine on PONV while considering the different anticholinergics as potentially confounding factors. We performed a systematic literature search using Medline, Embase, Cochrane library, reference listings, and hand searching with no language restriction through December 2004 and identified 10 clinical, randomized, controlled trials evaluating neostigmine's effect on PONV. Data on nausea or vomiting from 933 patients were extracted for the early (0-6 h), delayed (6-24 h), and overall postoperative periods (0-24 h) and analyzed with RevMan 4.2 (Cochrane Collaboration, Oxford, UK) and multiple logistic regression analysis. The combination of neostigmine with either atropine or glycopyrrolate did not significantly increase the incidence of overall (0-24 h) vomiting (relative risk (RR) 0.91 [0.70-1.18], P=0.48) or nausea (RR 1.24 [95% CI: 0.98-1.59], P=0.08). Multiple logistic regression analysis indicated that that there was not a significant increase in the risk of vomiting with large compared with small doses of neostigmine. In contrast to a previous analysis, we conclude that there is insufficient evidence to conclude that neostigmine increases the risk of PONV. PMID:16243993

Adherence to a Mediterranean diet is associated with lower prevalence of osteoarthritis: Data from the osteoarthritis initiative.

PubMed

Veronese, Nicola; Stubbs, Brendon; Noale, Marianna; Solmi, Marco; Luchini, Claudio; Smith, Toby O; Cooper, Cyrus; Guglielmi, Giuseppe; Reginster, Jean-Yves; Rizzoli, Renè; Maggi, Stefania

2017-12-01

The Mediterranean diet appears to be beneficial for several medical conditions, but data regarding osteoarthritis (OA) are not available. The aim of this study was to investigate if adherence to the Mediterranean diet is associated with a lower prevalence of OA of the knee in a large cohort from North America. 4358 community-dwelling participants (2527 females; mean age: 61.2 years) from the Osteoarthritis Initiative were included. Adherence to the Mediterranean diet was evaluated through a validated Mediterranean diet score (aMED) categorized into quartiles (Q). Knee OA was diagnosed both clinically and radiologically. The strength of the association between aMED (divided in quartiles) and knee OA was investigated through a logistic regression analysis and reported as odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders. Participants with a higher adherence to Mediterranean diet had a significantly lower prevalence of knee OA compared to those with lower adherence (Q4: 25.2% vs. Q1: 33.8%; p < 0.0001). Using a logistic regression analysis, adjusting for 10 potential confounders with those in the lowest quartile of aMED as reference, participants with the highest aMED had a significant reduction in presence of knee OA (OR, 0.83; 95% CIs: 0.69-0.99, p = 0.04). Among the individual components of Mediterranean diet, only higher use of cereals was associated with lower odds of having knee OA (OR: 0.76; 95%CI: 0.60-0.98; p = 0.03). Higher adherence to a Mediterranean diet is associated with lower prevalence of knee OA. This remained when adjusting for potential confounders. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Unfazed or Dazed and Confused: Does Early Adolescent Marijuana Use Cause Sustained Impairments in Attention and Academic Functioning?

PubMed Central

Pardini, Dustin; White, Helene; Xiong, Shuangyan; Bechtold, Jordan; Chung, Tammy; Loeber, Rolf; Hipwell, Alison

2015-01-01

There is some suggestion that heavy marijuana use during early adolescence (prior to age 17) may cause significant impairments in attention and academic functioning that remain following sustained periods of abstinence. However, no longitudinal studies have examined whether both male and female adolescents who engage in low (less than once a month) to moderate (at least once a monthly) marijuana use experience increased problems with attention and academic performance, and whether these problems remain following sustained abstinence. The current study used within-individual change models to control for all potential pre-existing and time-stable confounds when examining this potential causal association in two gender-specific longitudinal samples assessed annually from ages 11 to 16 (Pittsburgh Youth Study N=479; Pittsburgh Girls Study N=2296). Analyses also controlled for the potential influence of several pertinent time-varying factors (e.g., other substance use, peer delinquency). Prior to controlling for time-varying confounds, analyses indicated that adolescents tended to experience an increase in parent-reported attention and academic problems, relative to their pre-onset levels, during years when they used marijuana. After controlling for several time-varying confounds, only the association between marijuana use and attention problems in the sample of girls remained statistically significant. There was no evidence indicating that adolescents who used marijuana experienced lingering attention and academic problems, relative to their pre-onset levels, after abstaining from use for at least a year. These results suggest that adolescents who engage in low to moderate marijuana use experience an increase in observable attention and academic problems, but these problems appear to be minimal and are eliminated following sustained abstinence. PMID:25862212

Associations between Nausea, Vomiting, Fatigue and Health-Related Quality of Life of Women in Early Pregnancy: The Generation R Study.

PubMed

Bai, Guannan; Korfage, Ida J; Groen, Esther Hafkamp-de; Jaddoe, Vincent W V; Mautner, Eva; Raat, Hein

2016-01-01

The objective of this study was to evaluate the independent associations between nausea, vomiting, fatigue and health-related quality of life of women in early pregnancy in the Generation R study, which is a prospective mother and child cohort. Analyses were based on 5079 women in early pregnancy in the Rotterdam area, the Netherlands. The information on nausea, vomiting and fatigue in the previous three months was measured in the questionnaire at enrollment, as well as potential confounders (i.e., maternal/gestational age, ethnic background, educational level, parity, marital status, body mass index, tobacco and alcohol use, chronic/infectious conditions, uro-genital conditions/symptoms, sleep quality, headache, anxiety, and depression). Health-related quality of life was assessed by the 12-item Short Form Health Survey and physical and mental component summary scores were calculated. Multivariate regression models were performed to evaluate the independent associations of the presence of nausea, vomiting and fatigue with health-related quality of life, adjusting for potential confounders. 33.6% of women experienced daily presence of nausea, 9.6% for vomiting and 44.4% for fatigue. Comparing with women who never reported nausea, vomiting and fatigue, women with daily presence of at least one of these symptoms had significantly lower scores of physical component summary and mental component summary, after adjusting for potential confounders. Our study shows how common nausea, vomiting and fatigue are among women in early pregnancy and how much each of these symptoms negatively impact on health-related quality of life. We call for awareness of this issue from health care professionals, pregnant women and their families.

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.

Association of vitamin D status with metabolic syndrome and its components: A cross-sectional study in a population of high educated Iranian adults.

PubMed

Mansouri, Masoume; Abasi, Roshanak; Nasiri, Morteza; Sharifi, Farshad; Vesaly, Sedyghe; Sadeghi, Omid; Rahimi, Nayere; Sharif, Nasrin Akbary

2018-05-01

We aimed to assess the association of vitamin D status with metabolic syndrome and its components among high educated Iranian adults. In this cross-sectional study, 352 faculty members with age of 35 years or more, belong to Tarbiat Modares University, Tehran, Islamic Republic of Iran, were recruited during 2016 and 2017. Fasting blood samples were obtained to quantify serum 25(OH)D concentrations, glycemic indicators and lipid profile. Metabolic syndrome was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Multivariate logistic regression adjusted for potential confounders was used to evaluate the association between vitamin D status and metabolic syndrome. Metabolic syndrome and vitamin D insufficiency were prevalent among 26% and 60.2% of subjects, respectively. There was no statistically significant difference in the prevalence of metabolic syndrome across quartiles of 25(OH)D levels either before or after adjusting for potential confounders (OR: 0.94, 95% CI: 0.43-1.95). In terms of metabolic syndrome components, subjects in the highest quartile of vitamin D levels had 59% decreased risk of abdominal obesity compared with those in the lowest quartile (OR: 0.41, 95% CI: 0.17-0.99), after adjusting for potential confounders. Such inverse relationship was also seen for elevated blood pressure (OR: 0.37, 95% CI: 0.14-0.99), and abnormal glucose homeostasis (OR: 0.40, 95% CI: 0.19-0.85). Serum levels of 25(OH)D was inversely associated with the risk of abdominal obesity, hypertension, and abnormal glucose homeostasis. However, no significant relationship was seen for metabolic syndrome. Copyright © 2018. Published by Elsevier Ltd.

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.

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.

Unfazed or Dazed and Confused: Does Early Adolescent Marijuana Use Cause Sustained Impairments in Attention and Academic Functioning?

PubMed

Pardini, Dustin; White, Helene R; Xiong, Shuangyan; Bechtold, Jordan; Chung, Tammy; Loeber, Rolf; Hipwell, Alison

2015-10-01

There is some suggestion that heavy marijuana use during early adolescence (prior to age 17) may cause significant impairments in attention and academic functioning that remain despite sustained periods of abstinence. However, no longitudinal studies have examined whether both male and female adolescents who engage in low (less than once a month) to moderate (at least once a monthly) marijuana use experience increased problems with attention and academic performance, and whether these problems remain following sustained abstinence. The current study used within-individual change models to control for all potential pre-existing and time-stable confounds when examining this potential causal association in two gender-specific longitudinal samples assessed annually from ages 11 to 16 (Pittsburgh Youth Study N = 479; Pittsburgh Girls Study N = 2296). Analyses also controlled for the potential influence of several pertinent time-varying factors (e.g., other substance use, peer delinquency). Prior to controlling for time-varying confounds, analyses indicated that adolescents tended to experience an increase in parent-reported attention and academic problems, relative to their pre-onset levels, during years when they used marijuana. After controlling for several time-varying confounds, only the association between marijuana use and attention problems in the sample of girls remained statistically significant. There was no evidence indicating that adolescents who used marijuana experienced lingering attention and academic problems, relative to their pre-onset levels, after abstaining from use for at least a year. These results suggest that adolescents who engage in low to moderate marijuana use experience an increase in observable attention and academic problems, but these problems appear to be minimal and are eliminated following sustained abstinence.

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

PubMed

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

2015-09-01

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

Saturated fat intake modulates the association between a genetic risk score of obesity and BMI in two US populations

PubMed Central

Casas-Agustench, Patricia; Arnett, Donna K.; Smith, Caren E.; Lai, Chao-Qiang; Parnell, Laurence D.; Borecki, Ingrid B.; Frazier-Wood, Alexis C.; Allison, Matthew; Chen, Yii-Der Ida; Taylor, Kent D.; Rich, Stephen S.; Rotter, Jerome I.; Lee, Yu-Chi; Ordovás, José M.

2014-01-01

Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and BMI in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) population, focusing on gene-diet interactions with total fat and saturated fatty acid (SFA) intake and to replicate findings in Multi-Ethnic Study of Atherosclerosis (MESA) population. Cross-sectional analyses included 783 US Caucasian participants from GOLDN and 2035 from MESA. Dietary intakes were estimated with validated food frequency questionnaires. Height and weight were measured. A weighted GRS was calculated on the basis of 63 obesity-associated variants. Multiple linear regression models adjusted by potential confounders were used to examine gene-diet interactions between dietary intake (total fat and SFA) and the obesity GRS in determining BMI. Significant interactions were found between total fat intake and the obesity GRS using these variables as continuous for BMI (P for interaction=0.010, 0.046, and 0.002 in GOLDN, MESA and meta-analysis, respectively). These association terms were stronger when assessing interactions between SFA intake and GRS for BMI (P for interaction=0.005, 0.018, and <0.001 in GOLDN, MESA and meta-analysis, respectively). SFA intake interacts with an obesity GRS in modulating BMI in two US populations. Although to determine the causal direction requires further investigation, these findings suggest that potential dietary recommendations to reduce BMI effectively in populations with high obesity GRS would be to reduce total fat intake mainly by limiting SFAs. PMID:24794412

Ecologically-Relevant Maps of Landforms and Physiographic Diversity for Climate Adaptation Planning

PubMed Central

Theobald, David M.; Harrison-Atlas, Dylan; Monahan, William B.; Albano, Christine M.

2015-01-01

Key to understanding the implications of climate and land use change on biodiversity and natural resources is to incorporate the physiographic platform on which changes in ecological systems unfold. Here, we advance a detailed classification and high-resolution map of physiography, built by combining landforms and lithology (soil parent material) at multiple spatial scales. We used only relatively static abiotic variables (i.e., excluded climatic and biotic factors) to prevent confounding current ecological patterns and processes with enduring landscape features, and to make the physiographic classification more interpretable for climate adaptation planning. We generated novel spatial databases for 15 landform and 269 physiographic types across the conterminous United States of America. We examined their potential use by natural resource managers by placing them within a contemporary climate change adaptation framework, and found our physiographic databases could play key roles in four of seven general adaptation strategies. We also calculated correlations with common empirical measures of biodiversity to examine the degree to which the physiographic setting explains various aspects of current biodiversity patterns. Additionally, we evaluated the relationship between landform diversity and measures of climate change to explore how changes may unfold across a geophysical template. We found landform types are particularly sensitive to spatial scale, and so we recommend using high-resolution datasets when possible, as well as generating metrics using multiple neighborhood sizes to both minimize and characterize potential unknown biases. We illustrate how our work can inform current strategies for climate change adaptation. The analytical framework and classification of landforms and parent material are easily extendable to other geographies and may be used to promote climate change adaptation in other settings. PMID:26641818

Association Between Pain at Sites Outside the Knee and Knee Cartilage Volume Loss in Elderly People Without Knee Osteoarthritis: A Prospective Study.

PubMed

Pan, Feng; Laslett, Laura; Tian, Jing; Cicuttini, Flavia; Winzenberg, Tania; Ding, Changhai; Jones, Graeme

2017-05-01

Pain is common in the elderly. Knee pain may predict knee cartilage loss, but whether generalized pain is associated with knee cartilage loss is unclear. This study, therefore, aimed to determine whether pain at multiple sites predicts knee cartilage volume loss among community-dwelling older adults, and, if so, to explore potential mechanisms. Data from the prospective Tasmanian Older Adult Cohort study was utilized (n = 394, mean age 63 years, range 52-79 years). Experience of pain at multiple sites was assessed using a questionnaire at baseline. T1-weighted fat-saturated magnetic resonance imaging of the right knee was performed to assess the cartilage volume at baseline and after 2.6 years. Linear regression modeling was used with adjustment for potential confounders. The median number of painful sites was 3 (range 0-7). There was a dose-response relationship between the number of painful sites and knee cartilage volume loss in the lateral and total tibiofemoral compartments (lateral β = -0.28% per annum; total β = -0.25% per annum, both P for trend < 0.05), but not in the medial compartment. These associations were stronger in participants without radiographic knee osteoarthritis (OA) (P < 0.05) and independent of age, sex, body mass index, physical activity, pain medication, and knee structural abnormalities. The number of painful sites independently predicts knee cartilage volume loss, especially in people without knee OA, suggesting that widespread pain may be an early marker of more rapid knee cartilage loss in those without radiographic knee OA. The underlying mechanism is unclear, but it is independent of anthropometrics, physical activity, and knee structural abnormalities. © 2016, American College of Rheumatology.

Use of Single- versus Multiple-Fraction Palliative Radiation Therapy for Bone Metastases: Population-Based Analysis of 16,898 Courses in a Canadian Province

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

Olson, Robert A., E-mail: rolson2@bccancer.bc.ca; University of Northern British Columbia, Prince George, British Columbia; University of British Columbia, Vancouver, British Columbia

2014-08-01

Purpose: There is abundant evidence that a single fraction (SF) of palliative radiation therapy (RT) for bone metastases is equivalent to more protracted and costly multiple fraction courses. Despite this, there is low utilization of SFRT internationally. We sought to determine the utilization of SFRT in a population-based, publicly funded health care system. Methods and Materials: All consecutive patients with bone metastases treated with RT during 2007 to 2011 in British Columbia (BC) were identified. Associations between utilization of SFRT and patient and provider characteristics were investigated. Results: A total of 16,898 courses of RT were delivered to 8601 patients.more » SFRT was prescribed 49% of the time. There were positive relationships among SFRT utilization and primary tumor group (P<.001; most commonly in prostate cancer), worse prognosis (P<.001), increasing physician experience (P<.001), site of metastases (P<.001; least for spine metastases), and area of training (P<.001; most commonly for oncologists trained in the United Kingdom). There was wide variation in the prescription of SFRT across 5 regional cancer centers, ranging from 25.5% to 73.4%, which persisted after controlling for other, potentially confounding factors (P<.001). Conclusions: The large variability in SFRT utilization across BC Cancer Agency (BCCA) cancer centers suggests there is a strong cultural effect, where physicians' use of SFRT is influenced by their colleagues' practice. SFRT use in BC was similar to that in other Canadian and western European reports but strikingly higher than in the United States. Further work is needed to standardize SFRT prescribing practices internationally for this common indication for RT, with the potential for huge health system cost savings and substantial improvements in patients' quality of life.« less

Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

PubMed

Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

2014-08-01

Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

Raw garlic consumption as a protective factor for lung cancer, a population-based case-control study in a Chinese population

PubMed Central

Jin, Zi-Yi; Wu, Ming; Han, Ren-Qiang; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Zhou, Jin-Yi; Lu, Qing-Yi; Zhang, Zuo-Feng; Zhao, Jin-Kou

2013-01-01

Protective effect of garlic on the development of cancer has been reported in vitro and in vivo experimental studies, however, few human epidemiological studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiological data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was employed to estimate adjusted odds ratios (OR) and their 95% confidence intervals (CIs), and to evaluate ratio of odds ratios (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of ≥ 2 times per week is inversely associated with lung cancer (OR = 0.56, 95% CI = 0.44-0.72) with a monotonic dose-response relationship (p for trend <0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking (Synergy Index (SI) = 0.70, 95% CI = 0.57-0.85; and ROR = 0.78, 95% CI = 0.67-0.90), as well as high-temperature cooking oil fume (ROR = 0.77, 95% CI = 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation. PMID:23658367

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-11-01

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

Association between body mass index and health-related quality of life, and the impact of self-reported long-term conditions - cross-sectional study from the south Yorkshire cohort dataset.

PubMed

Kearns, Benjamin; Ara, Roberta; Young, Tracey; Relton, Clare

2013-10-25

We sought to quantify the relationship between body mass index (BMI) and health-related quality (HRQoL) of life, as measured by the EQ-5D, whilst controlling for potential confounders. In addition, we hypothesised that certain long-term conditions (LTCs), for which being overweight or obese is a known risk factor, may mediate the association between BMI and HRQoL. Hence the aim of our study was to explore the association between BMI and HRQoL, first controlling for confounders and then exploring the potential impact of LTCs. We used baseline data from the South Yorkshire Cohort, a cross-sectional observational study which uses a cohort multiple randomised controlled trial design. For each EQ-5D health dimension we used logistic regression to model the probability of responding as having a problem for each of the five health dimensions. All continuous variables were modelled using fractional polynomials. We examined the impact on the coefficients for BMI of removing LTCs from our model. We considered the self-reported LTCs: diabetes, heart disease, stroke, cancer, osteoarthritis, breathing problems and high blood pressure. The dataset used in our analysis had data for 19,460 individuals, who had a mean EQ-5D score of 0.81 and a mean BMI of 26.3 kg/m². For each dimension, BMI and all of the LTCs were significant predictors. For overweight or obese individuals (BMI ≥ 25 kg/m²), each unit increase in BMI was associated with approximately a 3% increase in the odds of reporting a problem for the anxiety/depression dimension, a 8% increase for the mobility dimension, and approximately 6% for the remaining dimension s. Diabetes, heart disease, osteoarthritis and high blood pressure were identified as being potentially mediating variables for all of the dimensions. Compared to those of a normal weight (18.5 < BMI < 25 kg/m²), overweight and obese individuals had a reduced HRQoL, with each unit increase in BMI associated with approximately a 6% increase in the odds of reporting a problem on any of the EQ-5D health dimensions. There was evidence to suggest that diabetes, heart disease, osteoarthritis and high blood pressure may mediate the association between being overweight and HRQoL.

Relationship between urban sprawl and physical activity, obesity, and morbidity - update and refinement.

PubMed

Ewing, Reid; Meakins, Gail; Hamidi, Shima; Nelson, Arthur C

2014-03-01

This study aims to model multiple health outcomes and behaviors in terms of the updated, refined, and validated county compactness/sprawl measures. Multiple health outcomes and behaviors are modeled using multi-level analysis. After controlling for observed confounding influences, both original and new compactness measures are negatively related to BMI, obesity, heart disease, high blood pressure, and diabetes. Indices are not significantly related to physical activity, perhaps because physical activity is not defined broadly to include active travel to work, shopping, and other destinations. Developing urban and suburban areas in a more compact manner may have some salutary effect on obesity and chronic disease trends. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Study Designs and Statistical Analyses for Biomarker Research

PubMed Central

Gosho, Masahiko; Nagashima, Kengo; Sato, Yasunori

2012-01-01

Biomarkers are becoming increasingly important for streamlining drug discovery and development. In addition, biomarkers are widely expected to be used as a tool for disease diagnosis, personalized medication, and surrogate endpoints in clinical research. In this paper, we highlight several important aspects related to study design and statistical analysis for clinical research incorporating biomarkers. We describe the typical and current study designs for exploring, detecting, and utilizing biomarkers. Furthermore, we introduce statistical issues such as confounding and multiplicity for statistical tests in biomarker research. PMID:23012528

[Integral quantitative evaluation of working conditions in the construction industry].

PubMed

Guseĭnov, A A

1993-01-01

Present method evaluating the quality of environment (using MAC and MAL) does not enable to assess completely and objectively the work conditions of building industry due to multiple confounding elements. A solution to this complicated problem including the analysis of various correlating elements of the system "human--work conditions--environment" may be encouraged by social norm of morbidity, which is independent on industrial and natural environment. The complete integral assessment enables to see the whole situation and reveal the points at risk.

Infrared Spectroscopic Imaging for Prostate Pathology Practice

DTIC Science & Technology

2010-03-01

lassification a lgorithm u ses mo rphological f eatures – geometric pr operties of epithelial cells/nuclei and lumens – that are quantified based on H&E stained...images as well as FT-IR images of the samples. By restricting the features used to geometric measures, we sought to m imic t he pa ttern r...be modeled as small elliptical areas in the stained images. This geometrical model is often confounded as multiple nuclei can be so close as to ap

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

PubMed Central

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

2017-01-01

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

Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case-control study protocol for dimethyl fumarate-induced lymphopenia.

PubMed

Kowalec, Kaarina; Kingwell, Elaine; Carruthers, Robert; Marrie, Ruth Ann; Bernatsky, Sasha; Traboulsee, Anthony; Ross, Colin J D; Carleton, Bruce; Tremlett, Helen

2017-06-02

Adverse drug reactions (ADRs) are a global public health issue. The potential for pharmacogenomic biomarkers has been demonstrated in several therapeutical areas, including HIV infection and oncology. Dimethyl fumarate (DMF) is a licensed disease-modifying therapy for the treatment of multiple sclerosis (MS). The use of DMF in MS has been associated with a severe reduction in lymphocyte counts and reports of progressive multifocal leukoencephalopathy. Here, we outline the protocol for a case-control study designed to discover genomic variants associated with DMF-induced lymphopenia. The ultimate goal is to replicate these findings and create an efficient and adaptable approach towards the identification of genomic markers that could assist in mitigating adverse drug reactions in MS. The population sample will comprise DMF-exposed patients with MS, with cases representing those who developed lymphopenia and controls who did not. DNA genotyping will take place using a high-throughput genome-wide array. Fine mapping and imputation will be performed to focus in on the potentially causal variants associated with lymphopenia. Multivariable logistic regression will be used to compare genotype and allele frequencies between the cases and the controls, with consideration of potential confounders. The association threshold will be set at p<1.0×10 -5 for the discovery of genomic association analyses to select variants for replication. Ethics approval has been obtained from the respective research ethics board, which includes written informed consent. Findings will be disseminated widely, including at scientific conferences, via podcasts (targeted at both healthcare professionals as well as patients and the wider community), through patient engagement and other outreach community events, written lay summaries for all participants and formal publication in peer-reviewed scientific journals. © 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.

Autofluorescence of atmospheric bioaerosols - fluorescent biomolecules and potential interferences

NASA Astrophysics Data System (ADS)

Pöhlker, C.; Huffman, J. A.; Pöschl, U.

2012-01-01

Primary biological aerosol particles (PBAP) are an important subset of air particulate matter with a substantial contribution to the organic aerosol fraction and potentially strong effects on public health and climate. Recent progress has been made in PBAP quantification by utilizing real-time bioaerosol detectors based on the principle that specific organic molecules of biological origin such as proteins, coenzymes, cell wall compounds and pigments exhibit intrinsic fluorescence. The properties of many fluorophores have been well documented, but it is unclear which are most relevant for detection of atmospheric PBAP. The present study provides a systematic synthesis of literature data on potentially relevant biological fluorophores. We analyze and discuss their relative importance for the detection of fluorescent biological aerosol particles (FBAP) by online instrumentation for atmospheric measurements such as the ultraviolet aerodynamic particle sizer (UV-APS) or the wide issue bioaerosol sensor (WIBS). In addition, we provide new laboratory measurement data for selected compounds using bench-top fluorescence spectroscopy. Relevant biological materials were chosen for comparison with existing literature data and to fill in gaps of understanding. The excitation-emission matrices (EEM) exhibit pronounced peaks at excitation wavelengths of ~280 nm and ~360 nm, confirming the suitability of light sources used for online detection of FBAP. They also show, however, that valuable information is missed by instruments that do not record full emission spectra at multiple wavelengths of excitation, and co-occurrence of multiple fluorophores within a detected sample will likely confound detailed molecular analysis. Selected non-biological materials were also analyzed to assess their possible influence on FBAP detection and generally exhibit only low levels of background-corrected fluorescent emission. This study strengthens the hypothesis that ambient supermicron particle fluorescence in wavelength ranges used for most FBAP instruments is likely to be dominated by biological material and that such instrumentation is able to discriminate between FBAP and non-biological material in many situations. More detailed follow-up studies on single particle fluorescence are still required to reduce these uncertainties further, however.

Autofluorescence of atmospheric bioaerosols - fluorescent biomolecules and potential interferences

NASA Astrophysics Data System (ADS)

Pöhlker, C.; Huffman, J. A.; Pöschl, U.

2011-09-01

Primary biological aerosol particles (PBAP) are an important subset of air particulate matter with a substantial contribution to the organic aerosol fraction and potentially strong effects on public health and climate. Recent progress has been made in PBAP quantification by utilizing real-time bioaerosol detectors based on the principle that specific organic molecules of biological origin such as proteins, coenzymes, cell wall compounds and pigments exhibit intrinsic fluorescence. The properties of many fluorophores have been well documented, but it is unclear which are most relevant for detection of atmospheric PBAP. The present study provides a systematic synthesis of literature data on potentially relevant biological fluorophores. We analyze and discuss their relative importance for the detection of fluorescent biological aerosol particles (FBAP) by online instrumentation for atmospheric measurements such as the ultraviolet aerodynamic particle sizer (UV-APS) or the wide issue bioaerosol sensor (WIBS). In addition, we provide new laboratory measurement data for selected compounds using bench-top fluorescence spectroscopy. Relevant biological materials were chosen for comparison with existing literature data and to fill in gaps of understanding. The excitation-emission matrices (EEM) exhibit pronounced peaks at excitation wavelengths of ~280 nm and ~360 nm, confirming the suitability of light sources used for online detection of FBAP. They also show, however, that valuable information is missed by instruments that do not record full emission spectra at multiple wavelengths of excitation, and co-occurrence of multiple fluorophores within a detected sample will likely confound detailed molecular analysis. Selected non-biological materials were also analyzed to assess their possible influence on FBAP detection and generally exhibit only low levels of background-corrected fluorescent emission. This study strengthens the hypothesis that ambient supermicron particle fluorescence in wavelength ranges used for most FBAP instruments is likely to be dominated by biological material and that such instrumentation is able to discriminate between FBAP and non-biological material in many situations. More detailed follow-up studies on single particle fluorescence are still required to reduce these uncertainties further, however.

Minorities Are Disproportionately Underrepresented in Special Education

ERIC Educational Resources Information Center

Morgan, Paul L.; Farkas, George; Hillemeier, Marianne M.; Mattison, Richard; Maczuga, Steve; Li, Hui; Cook, Michael

2015-01-01

We investigated whether minority children attending U.S. elementary and middle schools are disproportionately represented in special education. We did so using hazard modeling of multiyear longitudinal data and extensive covariate adjustment for potential child-, family-, and state-level confounds. Minority children were consistently less likely…

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 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.

Instrumental variable methods in comparative safety and effectiveness research†

PubMed Central

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

2010-01-01

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

Ultra-processed Food Intake and Obesity: What Really Matters for Health-Processing or Nutrient Content?

PubMed

Poti, Jennifer M; Braga, Bianca; Qin, Bo

2017-12-01

The aim of this narrative review was to summarize and critique recent evidence evaluating the association between ultra-processed food intake and obesity. Four of five studies found that higher purchases or consumption of ultra-processed food was associated with overweight/obesity. Additional studies reported relationships between ultra-processed food intake and higher fasting glucose, metabolic syndrome, increases in total and LDL cholesterol, and risk of hypertension. It remains unclear whether associations can be attributed to processing itself or the nutrient content of ultra-processed foods. Only three of nine studies used a prospective design, and the potential for residual confounding was high. Recent research provides fairly consistent support for the association of ultra-processed food intake with obesity and related cardiometabolic outcomes. There is a clear need for further studies, particularly those using longitudinal designs and with sufficient control for confounding, to potentially confirm these findings in different populations and to determine whether ultra-processed food consumption is associated with obesity independent of nutrient content.

Implantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats.

PubMed

Charng, Jason; He, Zheng; Bui, Bang; Vingrys, Algis; Ivarsson, Magnus; Fish, Rebecca; Gurrell, Rachel; Nguyen, Christine

2016-06-29

The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub-conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data.

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

PubMed Central

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

2015-01-01

Background Parental educational expectations have been associated with children’s educational attainment in a number of long-term longitudinal studies, but whether this relationship is causal has long been debated. The aims of this prospective study were twofold: 1) test whether low maternal educational expectations contributed to failure to graduate from high school; and 2) compare the results obtained using different strategies for accounting for confounding variables (i.e. multivariate regression and propensity score matching). Methodology/Principal Findings The study sample included 1,279 participants from the Quebec Longitudinal Study of Kindergarten Children. Maternal educational expectations were assessed when the participants were aged 12 years. High school graduation – measuring educational attainment – was determined through the Quebec Ministry of Education when the participants were aged 22–23 years. Findings show that when using the most common statistical approach (i.e. multivariate regressions to adjust for a restricted set of potential confounders) the contribution of low maternal educational expectations to failure to graduate from high school was statistically significant. However, when using propensity score matching, the contribution of maternal expectations was reduced and remained statistically significant only for males. Conclusions/Significance The results of this study are consistent with the possibility that the contribution of parental expectations to educational attainment is overestimated in the available literature. This may be explained by the use of a restricted range of potential confounding variables as well as the dearth of studies using appropriate statistical techniques and study designs in order to minimize confounding. Each of these techniques and designs, including propensity score matching, has its strengths and limitations: A more comprehensive understanding of the causal role of parental expectations will stem from a convergence of findings from studies using different techniques and designs. PMID:25803867

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.

Hypothyroidism and carpal tunnel syndrome: a meta-analysis.

PubMed

Shiri, Rahman

2014-12-01

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

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.

Neighborhood social capital and sleep duration: a population based cross-sectional study in a rural Japanese town.

PubMed

Win, Thida; Yamazaki, Toru; Kanda, Koji; Tajima, Kazuo; Sokejima, Shigeru

2018-03-12

Studies on social capital and health outcomes have become common, but the relationship between neighborhood social capital and sleep duration by gender is still unclear. We examined the relationship between neighborhood social capital and sleep duration by gender in adults living in a rural community in Japan. We conducted a cross-sectional survey of 12,321 residents aged ≥20 years in a town in Mie Prefecture in January-March 2013. Self-completed questionnaires were collected from the residents (n = 7782; valid participation rate, 63.2%). We used five items to assess the neighborhood social capital (Cronbach's α = 0.86). We summed up the scores of each item, and then divided the participants into four groups by quartile of total scores of neighborhood social capital (lowest, low, high, and highest). Sleep duration of < 7 h/day was defined as insufficient sleep duration according to previous studies. To adjust for potential confounders, we performed a multiple log-binominal regression analysis and estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) for insufficient sleep. Overall 42% of the men and 45% of the women had insufficient sleep. In the men, the lowest group of neighborhood social capital presented a 22% higher prevalence of insufficient sleep (PR 1.22; 95% CIs 1.08-1.38) compared to the highest group of neighborhood social capital. Similarly the low group of neighborhood social capital and the high group of neighborhood social capital had 20 and 19% higher prevalence of insufficient sleep (PR 1.20; 95% CIs 1.06-1.36; PR 1.19; 95% CIs 1.06-1.34, respectively) compared to the highest group of neighborhood social capital. For women there was no significant association between neighborhood social capital and insufficient sleep after controlling for all potential confounders. Having lower neighborhood social capital was associated with insufficient sleep among Japanese adults, particularly in the men. This suggests that the context of neighborhood social capital by gender should be considered to promote healthier behaviors with regard to getting enough sleep.

Role of stress in burnout among students of medicine and dentistry--a study in Ljubljana, Slovenia, Faculty of Medicine.

PubMed

Kogoj, Tina Krokter; Cebašek-Travnik, Zdenka; Zaletel-Kragelj, Lijana

2014-09-01

Medical education is challenging, but for some students it can be very stressful. Studies suggest that stress during medical education can have a negative impact on students' mental health and that burnout is frequent among medical school students. The aim of this study was to measure burnout among students of medicine/dentistry (M/D) at the Faculty of Medicine, University of Ljubljana, Slovenia, in relation to their perception of stress, so as to enable planning preventative activities for students at risk. The data were collected in a cross-sectional study, carried out in spring 2008 among the total population of MID students of 1St, 3rd, 4th and 6th year, using a self-administered online questionnaire. Oldenburg Burnout Inventory (OLBI) instrument was used. Separate burnout scores were calculated for the exhaustion and disengagement dimensions of burnout, and related to students'perception of stress. Multiple linear regression method was carried out to adjust the association estimates for several potential confounders (gender, study program, relationship status, and grade). The overall response rate was 47.2%, and a total of 476 students participated. Students scored higher on exhaustion than on disengagement dimension--the mean value of burnout scores on the exhaustion dimension scale was -1.68, while it was -4.58 on the disengagement dimension scale. The results showed a statistically significant difference between high and low risk-for-stress groups of students in both burnout dimensions (average value of burnout scores on the exhaustion scale: high risk-for-stress group -3.69, low risk-for-stress group 0.19, p<0.001; average value of burnout scores on the disengagement scale: high risk-for-stress group -5.57, low risk-for-stress group -3.65, p<0.001). After adjustment for potential confounders differences on both burnout subscales remained almost unchanged. Results confirmed our hypothesis that M/D students of Ljubljana Faculty of Medicine who frequently experience stress (especially those with poor coping mechanisms), exhibit higher degree of burnout.

Maternal early pregnancy body mass index and risk of preterm birth.

PubMed

Wang, Ting; Zhang, Jun; Lu, Xinrong; Xi, Wei; Li, Zhu

2011-10-01

To determine the association between maternal body mass index (BMI) in early pregnancy and the risk of preterm birth (PTB) in Chinese women. Data were obtained from a population-based perinatal care program in China during 1993-2005. Women whose height and weight information was recorded at the first prenatal visit in the first trimester of pregnancy and delivered a singleton live infant were selected. Women with multiple gestations, stillbirths, delivery before 28 weeks or after 44 weeks of gestation, and infants affected by major external birth defects were excluded. BMI was categorized as underweight (less than 18.5 kg/m(2)), normal weight (18.5-23.9 kg/m(2)), overweight (24-27.9 kg/m(2)), and obese (≥28 kg/m(2)) based on BMI classification criteria for Chinese. Logistic regression analysis was conducted to adjust for potential confounders, such as maternal age, education, occupation, city or county, gender of infant, and year of delivery. A total of 353,477 women were selected. The incidence of preterm birth in women who were underweight, normal weight, overweight, obese was 3.69% (3.61-3.76%), 3.59% (3.55-3.62%), 3.83% (3.71-3.96%), 4.90% (4.37-5.43%), respectively. The incidence of elective preterm birth, overweight, and obesity increased remarkably during 2000-2005 compared with that during 1993-1996. After having adjusted for potential confounders including maternal age, maternal occupation, education, city or county, gender of the infant and year of birth, the risk of PTB increased significantly with BMI (P < 0.05). Among nulliparae, the risk of elective preterm birth increased with increasing BMI. Nulliparae who were underweight were less likely to deliver elective preterm births (OR = 0.89, 95% CI 0.80-0.98). Nulliparae who were overweight and obese in early pregnancy were at a greater risk of elective PTB than normal weight nulliparae (for the overweight OR = 1.36, 95% CI 1.18-1.56, for the obese OR = 2.94, 95% CI 2.04-4.25). In this study, indigenous Chinese cohort women who are overweight, obese, and nulliparous are at an increased risk of elective preterm birth.

Association Between Hospitals Caring for a Disproportionately High Percentage of Minority Trauma Patients and Increased Mortality

PubMed Central

Haider, Adil H.; Ong’uti, Sharon; Efron, David T.; Oyetunji, Tolulope A.; Crandall, Marie L.; Scott, Valerie K.; Haut, Elliott R.; Schneider, Eric B.; Powe, Neil R.; Cooper, Lisa A.; Cornwell, Edward E.

2012-01-01

Objective To determine whether there is an increased odds of mortality among trauma patients treated at hospitals with higher proportions of minority patients (ie, black and Hispanic patients combined). Design Hospitals were categorized on the basis of the percentage of minority patients admitted with trauma. The adjusted odds of in-hospital mortality were compared between hospitals with less than 25% of patients who were minorities (the reference group) and hospitals with 25% to 50% of patients who were minorities and hospitals with more than 50% of patients who were minorities. Multivariate logistic regression (with generalized linear modeling and a cluster-correlated robust estimate of variance) was used to control for multiple patient and injury severity characteristics. Setting A total of 434 hospitals in the National Trauma Data Bank. Participants Patients aged 18 to 64 years whose medical records were included in the National Trauma Data Bank for the years 2007 and 2008 with an Injury Severity Score of 9 or greater and who were white, black, or Hispanic. Main Outcome Measures Crude mortality and adjusted odds of in-hospital mortality. Results A total of 311 568 patients were examined. Hospitals in which the percentage of minority patients was more than 50% also had younger patients, fewer female patients, more patients with penetrating trauma, and the highest crude mortality. After adjustment for potential confounders, patients treated at hospitals in which the percentage of minority patients was 25% to 50% and at hospitals in which the percentage of minority patients was more than 50% demonstrated increased odds of death (adjusted odds ratio, 1.16 [95% confidence interval, 1.01–1.34] and adjusted odds ratio, 1.37 [95% confidence interval, 1.16–1.61], respectively), compared with the reference group. This disparity increased further on subset analysis of patients with a blunt injury. Uninsured patients had significantly increased odds of mortality within all 3 hospital groups. Conclusions Patients treated at hospitals with higher proportions of minority trauma patients have increased odds of dying, even after adjusting for potential confounders. Differences in outcomes between trauma hospitals may partly explain racial disparities. PMID:21930976

The risk of adolescent suicide across patterns of drug use: a nationally representative study of high school students in the United States from 1999 to 2009.

PubMed

Wong, Shane Shucheng; Zhou, Bo; Goebert, Deborah; Hishinuma, Earl S

2013-10-01

Substance use is associated with suicidal ideation, planning and attempts among adolescents, but it is unclear how this association varies across different types and number of substances. This study examined the association between patterns of substance use and suicidality among a nationally representative sample of high school students in the United States during the last decade. Data from the 2001 to 2009 Youth Risk Behavior Survey including 73,183 high school students were analyzed. Logistic regression analyses examined the association between lifetime use of ten common substances of abuse (alcohol, cocaine, ecstasy, hallucinogens, heroin, inhalants, marijuana, methamphetamines, steroids, and tobacco) and four measures of suicidality over the last year (suicidal ideation, suicide plan, suicide attempt, and severe suicide attempt requiring medical attention), controlling for potential confounders (socio-demographic variables, interpersonal violence, sexual intercourse, and symptoms of depression and eating disorder). Among the ten substances, univariate analysis demonstrates that adolescents reporting a history of heroin use have the strongest association with suicidal ideation, suicide plan, suicide attempts and severe suicide attempts in the last year (odds ratio = 5.0, 5.9, 12.0, and 23.6 compared to non-users), followed by users of methamphetamines (OR = 4.3-13.1) and steroids (OR = 3.7-11.8). Cocaine, ecstasy, hallucinogens and inhalants had a moderate association with suicidality (OR = 3.1-10.8). Users of marijuana, alcohol and tobacco also had an increased odds ratio of suicidality (OR = 1.9-5.2). The association between each of ten substances and the four measures of suicidality remained significant with multivariate analysis controlling for multiple confounders (p < 0.05), except for the association between alcohol use and severe suicide attempts. The seven illicit substances had a stronger association with severe suicide attempts as compared to all other confounding risk factors except depression. The number of substances used had a graded relationship to suicidality. Substance abuse is a strong risk factor for suicidal thoughts and behaviors among American high school students, with the strength of this relationship dramatically increasing with particular illicit drugs and a higher number of substances. The findings reinforce the importance of routine screening for substance abuse in the assessment of adolescent suicide risk.

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

PubMed

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

2010-05-01

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

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

PubMed Central

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

2013-01-01

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

The impact of HIV status, HIV disease progression, and post-traumatic stress symptoms on the health-related quality of life of Rwandan women genocide survivors.

PubMed

Gard, Tracy L; Hoover, Donald R; Shi, Qiuhu; Cohen, Mardge H; Mutimura, Eugene; Adedimeji, Adebola A; Anastos, Kathryn

2013-10-01

We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV-infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression. The Rwandan Women's Interassociation Study and Assessment was a longitudinal prospective study of HIV-infected and uninfected women. At study entry, 922 women (705 HIV+ and 217 HIV-) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical, and behavioral characteristics. Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall quality of life (QOL) than did HIV- women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms. This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long-term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL.

Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study.

PubMed

Bateman, Brian T; Huybrechts, Krista F; Fischer, Michael A; Seely, Ellen W; Ecker, Jeffrey L; Oberg, Anna S; Franklin, Jessica M; Mogun, Helen; Hernandez-Diaz, Sonia

2015-03-01

Chronic hypertension is a common medical condition in pregnancy. The purpose of the study was to examine the association between maternal chronic hypertension and the risk of congenital malformations in the offspring. We defined a cohort of 878,126 completed pregnancies linked to infant medical records using the Medicaid Analytic Extract. The risk of congenital malformations was compared between normotensive controls and those with treated and untreated chronic hypertension. Confounding was addressed using propensity score matching. After matching, compared with normotensive controls, pregnancies complicated by treated chronic hypertension were at increased risk of congenital malformations (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.5), as were pregnancies with untreated chronic hypertension (OR 1.2; 95% CI, 1.1-1.3). In our analysis of organ-specific malformations, both treated and untreated chronic hypertension was associated with a significant increase in the risk of cardiac malformations (OR, 1.6; 95% CI, 1.4-1.9 and OR, 1.5; 95% CI, 1.3-1.7, respectively). These associations persisted across a range of sensitivity analyses. There is a similar increase in the risk of congenital malformations (particularly cardiac malformations) associated with treated and untreated chronic hypertension that is independent of measured confounders. Studies evaluating the teratogenic potential of antihypertensive medications must control for confounding by indication. Fetuses and neonates of mothers with chronic hypertension should be carefully evaluated for potential malformations, particularly cardiac defects. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

The Impact of HIV Status, HIV Disease Progression and Post-Traumatic Stress Symptoms on the Health-Related Quality of Life of Rwandan Women Genocide Survivors

PubMed Central

Gard, Tracy L.; Hoover, Donald R.; Shi, Qiuhu; Cohen, Mardge H.; Mutimura, Eugene; Adedimeji, Adebola A.; Anastos, Kathryn

2014-01-01

Purpose We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression. Methods The Rwandan Women’s Interassociation Study and Assessment (RWISA) was a longitudinal prospective study of HIV-infected and uninfected women. At study entry 922 women (705 HIV+ and 217 HIV−) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical and behavioral characteristics. Results Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall QOL than did HIV− women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms. Conclusions This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL. PMID:23271207

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.

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

PubMed

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

2015-10-01

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

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

PubMed

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

2014-06-01

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

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study.

PubMed

Laprise, Claudie; Shahul, Hameed Puthiyannal; Madathil, Sreenath Arekunnath; Thekkepurakkal, Akhil Soman; Castonguay, Geneviève; Varghese, Ipe; Shiraz, Shameena; Allison, Paul; Schlecht, Nicolas F; Rousseau, Marie-Claude; Franco, Eduardo L; Nicolau, Belinda

2016-10-01

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer. © 2016 UICC.

Differential Covariance: A New Class of Methods to Estimate Sparse Connectivity from Neural Recordings

PubMed Central

Lin, Tiger W.; Das, Anup; Krishnan, Giri P.; Bazhenov, Maxim; Sejnowski, Terrence J.

2017-01-01

With our ability to record more neurons simultaneously, making sense of these data is a challenge. Functional connectivity is one popular way to study the relationship of multiple neural signals. Correlation-based methods are a set of currently well-used techniques for functional connectivity estimation. However, due to explaining away and unobserved common inputs (Stevenson, Rebesco, Miller, & Körding, 2008), they produce spurious connections. The general linear model (GLM), which models spike trains as Poisson processes (Okatan, Wilson, & Brown, 2005; Truccolo, Eden, Fellows, Donoghue, & Brown, 2005; Pillow et al., 2008), avoids these confounds. We develop here a new class of methods by using differential signals based on simulated intracellular voltage recordings. It is equivalent to a regularized AR(2) model. We also expand the method to simulated local field potential recordings and calcium imaging. In all of our simulated data, the differential covariance-based methods achieved performance better than or similar to the GLM method and required fewer data samples. This new class of methods provides alternative ways to analyze neural signals. PMID:28777719

Differential Covariance: A New Class of Methods to Estimate Sparse Connectivity from Neural Recordings.

PubMed

Lin, Tiger W; Das, Anup; Krishnan, Giri P; Bazhenov, Maxim; Sejnowski, Terrence J

2017-10-01

With our ability to record more neurons simultaneously, making sense of these data is a challenge. Functional connectivity is one popular way to study the relationship of multiple neural signals. Correlation-based methods are a set of currently well-used techniques for functional connectivity estimation. However, due to explaining away and unobserved common inputs (Stevenson, Rebesco, Miller, & Körding, 2008 ), they produce spurious connections. The general linear model (GLM), which models spike trains as Poisson processes (Okatan, Wilson, & Brown, 2005 ; Truccolo, Eden, Fellows, Donoghue, & Brown, 2005 ; Pillow et al., 2008 ), avoids these confounds. We develop here a new class of methods by using differential signals based on simulated intracellular voltage recordings. It is equivalent to a regularized AR(2) model. We also expand the method to simulated local field potential recordings and calcium imaging. In all of our simulated data, the differential covariance-based methods achieved performance better than or similar to the GLM method and required fewer data samples. This new class of methods provides alternative ways to analyze neural signals.

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 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).

Relationship between perceived body image and recorded body mass index among Kuwaiti female university students.

PubMed

Kabir, Yearul; Zafar, Tasleem A; Waslien, Carol

2013-01-01

The associations between body image and attitudes toward obesity and thinness and their associations with measured body mass index (BMI) among female students of Kuwait University (n = 137) was examined in 2008. The body image perceptions were assessed using nine female silhouettes figures. The difference between current perceived body image (PBI) and ideal body image (IBI) was used as a measure of body image dissatisfaction (BID). Students tended to have a bigger PBI and smaller IBI than would be expected from their BMI category, leading to high levels of BID in each BMI category. PBI, IBI, BID, RBI were highly correlated with each other, and BMI was significantly correlated with each of them. The coefficients of these associations were not significantly altered in multiple regression analysis by the addition of potential confounding variables, such as age, marital status, physical activity, dieting behavior, parental education, and family size. These results suggest that PBI and a desire to be thinner were strongly related to BID and that thinness is becoming more desired in Kuwaiti society than the plump body image of the past.

Neuromotor outcomes in infants with bronchopulmonary dysplasia.

PubMed

Karagianni, Paraskevi; Tsakalidis, Christos; Kyriakidou, Maria; Mitsiakos, Georgios; Chatziioanidis, Helias; Porpodi, Maria; Evangeliou, Athanasios; Nikolaides, Nikolaos

2011-01-01

We examine the neuromotor outcomes of preterm infants with bronchopulmonary dysplasia. Two hundred and nineteen infants (gestational age, ≤ 32 weeks; birth weight, ≤ 1500 g) were studied. Neuromotor development was assessed using the Hammersmith Infant Neurological Examination. All potential risk factors associated with neuromotor scores (P < 0.015) were included in the generalized linear model (multiple linear regression) to determine if bronchopulmonary dysplasia had an independent relationship with neuromotor scores. Infants with severe bronchopulmonary dysplasia had lower global scores at ages 6 and 12 months. After adjustment for confounding factors, scores of infants with severe bronchopulmonary dysplasia were reduced by 13.2 units, whereas scores for those with periventricular leukomalacia were reduced by 11.1 units, at age 6 months. At age 12 months, scores for those with periventricular leukomalacia were reduced by 11.9 units. Duration of hospital stay reduced scores by 0.1 for each additional day increase in hospital. Bronchopulmonary dysplasia constitutes a major cause of poor neuromotor outcomes at age 6 months, but improvements in motor outcomes occur over time. Copyright © 2011 Elsevier Inc. All rights reserved.

Management of acute attacks of hereditary angioedema: potential role of icatibant

PubMed Central

Longhurst, Hilary J

2010-01-01

Icatibant (Firazyr®) is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema. PMID:20859548

Metabolic risk and television time in adolescent females.

PubMed

Machado-Rodrigues, Aristides M; Leite, Neiva; Coelho-e-Silva, Manuel J; Enes, Fernando; Fernandes, Rômulo; Mascarenhas, Luís P G; Boguszewski, Margaret C S; Malina, Robert M

2015-02-01

A sedentary lifestyle is increasingly implicated in a negative metabolic health profile among youth. The present study examined relationships between clustered metabolic risk factors and TV viewing in female adolescents. The sample comprised 262 girls 14-17 years. Height, weight, fasting glucose, insulin, HDL cholesterol, triglycerides, and blood pressure were measured. Body mass index (BMI) was calculated. TV viewing time and moderate-to-vigorous physical activity (MVPA) were estimated from a 3-day diary. Outcome variables were normalized and expressed as Z scores which were summed into a metabolic risk score. Multiple linear regression analysis was used. TV viewing was independently associated with increased prevalence of clustered metabolic risk in girls after adjustment for several confounders (i.e., chronological age, BMI, MVPA, and parental education). The final model also indicated that lower levels of MVPA, higher BMI, and lower mother education were associated with higher metabolic risk. Increased TV viewing had an adverse effect on metabolic health of adolescent girls. The findings highlight the potential importance of preventive actions to ameliorate metabolic risk in youth which target both sedentary and physically active behaviors.

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

EPA Science Inventory

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

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

USDA-ARS?s Scientific Manuscript database

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

Brief Report: Life History and Neuropathology of a Gifted Man with Asperger Syndrome

ERIC Educational Resources Information Center

Weidenheim, Karen, M.; Escobar, Alfonso; Rapin, Isabelle

2012-01-01

Despite recent interest in the pathogenesis of the autism spectrum disorders (pervasive developmental disorders), neuropathological descriptions of brains of individuals with well documented clinical information and without potentially confounding symptomatology are exceptionally rare. Asperger syndrome differs from classic autism by lack of…

Lack of association between JAK3 gene polymorphisms and cardiovascular disease in Spanish patients with rheumatoid arthritis.

PubMed

García-Bermúdez, Mercedes; López-Mejías, Raquel; Genre, Fernanda; Castañeda, Santos; Corrales, Alfonso; Llorca, Javier; González-Juanatey, Carlos; Ubilla, Begoña; Miranda-Filloy, José A; Pina, Trinitario; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Pascual-Salcedo, Dora; López-Longo, Francisco J; Carreira, Patricia; Blanco, Ricardo; Martín, Javier; González-Gay, Miguel A

2015-01-01

Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. JAK/STAT signalling pathway is involved in autoimmune diseases and in the atherosclerotic process. JAK3 is a highly promising target for immunomodulatory drugs and polymorphisms in JAK3 gene have been associated with CV events in incident dialysis patients. Therefore, the aim of this study was to assess the potential role of JAK3 polymorphisms in the development of CV disease in patients with RA. 2136 Spanish RA patients were genotyped for the rs3212780 and rs3212752 JAK3 gene polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 539 of these patients by carotid ultrasonography (US). No statistically significant differences were found when each polymorphism was assessed according to carotid intima-media thickness values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV events after adjusting for potential confounders. In conclusion, our results do not confirm association between JAK3 polymorphisms and CV disease in RA.

Lack of Association between JAK3 Gene Polymorphisms and Cardiovascular Disease in Spanish Patients with Rheumatoid Arthritis

PubMed Central

García-Bermúdez, Mercedes; López-Mejías, Raquel; Castañeda, Santos; Corrales, Alfonso; González-Juanatey, Carlos; Ubilla, Begoña; Miranda-Filloy, José A.; Pina, Trinitario; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Pascual-Salcedo, Dora; López-Longo, Francisco J.; Carreira, Patricia; Blanco, Ricardo; Martín, Javier; González-Gay, Miguel A.

2015-01-01

Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. JAK/STAT signalling pathway is involved in autoimmune diseases and in the atherosclerotic process. JAK3 is a highly promising target for immunomodulatory drugs and polymorphisms in JAK3 gene have been associated with CV events in incident dialysis patients. Therefore, the aim of this study was to assess the potential role of JAK3 polymorphisms in the development of CV disease in patients with RA. 2136 Spanish RA patients were genotyped for the rs3212780 and rs3212752 JAK3 gene polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 539 of these patients by carotid ultrasonography (US). No statistically significant differences were found when each polymorphism was assessed according to carotid intima-media thickness values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV events after adjusting for potential confounders. In conclusion, our results do not confirm association between JAK3 polymorphisms and CV disease in RA. PMID:25815310

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

Local Field Potentials: Myths and Misunderstandings

PubMed Central

Herreras, Oscar

2016-01-01

The intracerebral local field potential (LFP) is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a composite signal that receives contributions from multiple neural sources, yet interpreting its nature and significance may be hindered by several confounding factors and technical limitations. By and large, the main factor defining the amplitude of LFPs is the geometry of the current sources, over and above the degree of synchronization or the properties of the media. As such, similar levels of activity may result in potentials that differ in several orders of magnitude in different populations. The geometry of these sources has been experimentally inaccessible until intracerebral high density recordings enabled the co-activating sources to be revealed. Without this information, it has proven difficult to interpret a century's worth of recordings that used temporal cues alone, such as event or spike related potentials and frequency bands. Meanwhile, a collection of biophysically ill-founded concepts have been considered legitimate, which can now be corrected in the light of recent advances. The relationship of LFPs to their sources is often counterintuitive. For instance, most LFP activity is not local but remote, it may be larger further from rather than close to the source, the polarity does not define its excitatory or inhibitory nature, and the amplitude may increase when source's activity is reduced. As technological developments foster the use of LFPs, the time is now ripe to raise awareness of the need to take into account spatial aspects of these signals and of the errors derived from neglecting to do so. PMID:28018180

Predicting Fish Growth Potential and Identifying Water Quality Constraints: A Spatially-Explicit Bioenergetics Approach

NASA Astrophysics Data System (ADS)

Budy, Phaedra; Baker, Matthew; Dahle, Samuel K.

2011-10-01

Anthropogenic impairment of water bodies represents a global environmental concern, yet few attempts have successfully linked fish performance to thermal habitat suitability and fewer have distinguished co-varying water quality constraints. We interfaced fish bioenergetics, field measurements, and Thermal Remote Imaging to generate a spatially-explicit, high-resolution surface of fish growth potential, and next employed a structured hypothesis to detect relationships among measures of fish performance and co-varying water quality constraints. Our thermal surface of fish performance captured the amount and spatial-temporal arrangement of thermally-suitable habitat for three focal species in an extremely heterogeneous reservoir, but interpretation of this pattern was initially confounded by seasonal covariation of water residence time and water quality. Subsequent path analysis revealed that in terms of seasonal patterns in growth potential, catfish and walleye responded to temperature, positively and negatively, respectively; crappie and walleye responded to eutrophy (negatively). At the high eutrophy levels observed in this system, some desired fishes appear to suffer from excessive cultural eutrophication within the context of elevated temperatures whereas others appear to be largely unaffected or even enhanced. Our overall findings do not lead to the conclusion that this system is degraded by pollution; however, they do highlight the need to use a sensitive focal species in the process of determining allowable nutrient loading and as integrators of habitat suitability across multiple spatial and temporal scales. We provide an integrated approach useful for quantifying fish growth potential and identifying water quality constraints on fish performance at spatial scales appropriate for whole-system management.

Strange Words: Autistic Traits and the Processing of Non-Literal Language.

PubMed

McKenna, Peter E; Glass, Alexandra; Rajendran, Gnanathusharan; Corley, Martin

2015-11-01

Previous investigations into metonymy comprehension in ASD have confounded metonymy with anaphora, and outcome with process. Here we show how these confounds may be avoided, using data from non-diagnosed participants classified using Autism Quotient. Participants read sentences containing target words with novel or established metonymic senses (e.g., Finland, Vietnam) in literal- or figurative-supporting contexts. Participants took longer to read target words in figurative contexts, especially where the metonymic sense was novel. Importantly, participants with higher AQs took longer still to read novel metonyms. This suggests a focus for further exploration, in terms of potential differences between individuals diagnosed with ASD and their neurotypical counterparts, and more generally in terms of the processes by which comprehension is achieved.

Modeling Gene-Environment Interactions With Quasi-Natural Experiments.

PubMed

Schmitz, Lauren; Conley, Dalton

2017-02-01

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

Construct Validation of the Dietary Inflammatory Index among Postmenopausal Women

PubMed Central

Tabung, Fred K.; Steck, Susan E.; Zhang, Jiajia; Ma, Yunsheng; Liese, Angela D.; Agalliu, Ilir; Hingle, Melanie; Hou, Lifang; Hurley, Thomas G.; Jiao, Li; Martin, Lisa W.; Millen, Amy E.; Park, Hannah L.; Rosal, Milagros C.; Shikany, James M.; Shivappa, Nitin; Ockene, Judith K.; Hebert, James R.

2015-01-01

Purpose Many dietary factors have either pro- or anti-inflammatory properties. We previously developed a dietary inflammatory index (DII) to assess the inflammatory potential of diet. In this study we conducted a construct validation of the DII based on data from a food frequency questionnaire and three inflammatory biomarkers in a subsample of 2,567 postmenopausal women in the Women’s Health Initiative Observational Study. Methods We used multiple linear and logistic regression models, controlling for potential confounders, to test whether baseline DII predicted concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha receptor 2 (TNFα-R2), or an overall biomarker score combining all three inflammatory biomarkers. Results The DII was associated with the four biomarkers with beta estimates (95%CI) comparing the highest with lowest DII quintiles as follows: IL-6: 1.26 (1.15, 1.38), Ptrend<0.0001; TNFα-R2: 81.43 (19.15, 143.71), Ptrend=0.004; dichotomized hs-CRP (odds ratio for higher versus lower hs-CRP): 1.30 (0.97, 1.67), Ptrend=0.34); and the combined inflammatory biomarker score: 0.26 (0.12, 0.40), Ptrend=0.0001. Conclusion The DII was significantly associated with inflammatory biomarkers. Construct validity of the DII indicates its utility for assessing the inflammatory potential of diet and for expanding its use to include associations with common chronic diseases in future studies. PMID:25900255

Field evidence for pervasive indirect effects of fishing on prey foraging behavior.

PubMed

Madin, Elizabeth M P; Gaines, Steven D; Warner, Robert R

2010-12-01

The indirect, ecosystem-level consequences of ocean fishing, and particularly the mechanisms driving them, are poorly understood. Most studies focus on density-mediated trophic cascades, where removal of predators alternately causes increases and decreases in abundances of lower trophic levels. However, cascades could also be driven by where and when prey forage rather than solely by prey abundance. Over a large gradient of fishing intensity in the central Pacific's remote northern Line Islands, including a nearly pristine, baseline coral reef system, we found that changes in predation risk elicit strong behavioral responses in foraging patterns across multiple prey fish species. These responses were observed as a function of both short-term ("acute") risk and longer-term ("chronic") risk, as well as when prey were exposed to model predators to isolate the effect of perceived predation risk from other potentially confounding factors. Compared to numerical prey responses, antipredator behavioral responses such as these can potentially have far greater net impacts (by occurring over entire assemblages) and operate over shorter temporal scales (with potentially instantaneous response times) in transmitting top-down effects. A rich body of literature exists on both the direct effects of human removal of predators from ecosystems and predators' effects on prey behavior. Our results draw together these lines of research and provide the first empirical evidence that large-scale human removal of predators from a natural ecosystem indirectly alters prey behavior. These behavioral changes may, in turn, drive previously unsuspected alterations in reef food webs.

Malnutrition at age 3 years and lower cognitive ability at age 11 years: independence from psychosocial adversity.

PubMed

Liu, Jianghong; Raine, Adrian; Venables, Peter H; Dalais, Cyril; Mednick, Sarnoff A

2003-06-01

Early malnutrition is linked to poor cognition, but long-term effects have not been extensively examined and psychosocial confounds have not always been controlled. To test the hypothesis that malnutrition at age 3 years will be associated with poorer cognitive ability at age 11 years independent of psychosocial confounds. A prospective, longitudinal study of a birth cohort of 1559 children originally assessed at age 3 years for malnutrition (low hemoglobin level, angular stomatitis, kwashiorkor, and sparse, thin hair) and followed up to age 11 years. A community sample of 1559 children (51.4% boys and 48.6% girls) born between September 1, 1969, and August 31, 1970, in 2 towns in the island of Mauritius, with 68.7% Indians and 25.7% Creoles (African origin). Verbal and spatial ability measured at ages 3 and 11 years and reading, scholastic ability, and neuropsychologic performance measured at age 11 years. Malnourished children had poorer cognition at both ages. Deficits were stable across time, applied to all sex and ethnic groups, and remained after controlling for multiple measures of psychosocial adversity. Children with 3 indicators of malnutrition had a 15.3-point deficit in IQ at age 11 years. Malnutrition at age 3 years is associated with poor cognition at age 11 years independent of psychosocial adversity. Promoting early childhood nutrition could enhance long-term cognitive development and school performance, especially in children with multiple nutritional deficits.

Malnutrition at Age 3 Years and Lower Cognitive Ability at Age 11 Years

PubMed Central

Liu, Jianghong; Raine, Adrian; Venables, Peter H.; Dalais, Cyril; Mednick, Sarnoff A.

2014-01-01

Background Early malnutrition is linked to poor cognition, but long-term effects have not been extensively examined and psychosocial confounds have not always been controlled. Objective To test the hypothesis that malnutrition at age 3 years will be associated with poorer cognitive ability at age 11 years independent of psychosocial confounds. Design A prospective, longitudinal study of a birth cohort of 1559 children originally assessed at age 3 years for malnutrition (low hemoglobin level, angular stomatitis, kwashiorkor, and sparse, thin hair) and followed up to age 11 years. Setting and Participants A community sample of 1559 children (51.4% boys and 48.6% girls) born between September 1, 1969, and August 31, 1970, in 2 towns in the island of Mauritius, with 68.7% Indians and 25.7% Creoles (African origin). Main Outcome Measures Verbal and spatial ability measured at ages 3 and 11 years and reading, scholastic ability, and neuropsychologic performance measured at age 11 years. Results Malnourished children had poorer cognition at both ages. Deficits were stable across time, applied to all sex and ethnic groups, and remained after controlling for multiple measures of psychosocial adversity. Children with 3 indicators of malnutrition had a 15.3-point deficit in IQ at age 11 years. Conclusions Malnutrition at age 3 years is associated with poor cognition at age 11 years independent of psychosocial adversity. Promoting early childhood nutrition could enhance long-term cognitive development and school performance, especially in children with multiple nutritional deficits. PMID:12796242

Part-to-itself model inversion in process compensated resonance testing

NASA Astrophysics Data System (ADS)

Mayes, Alexander; Jauriqui, Leanne; Biedermann, Eric; Heffernan, Julieanne; Livings, Richard; Aldrin, John C.; Goodlet, Brent; Mazdiyasni, Siamack

2018-04-01

Process Compensated Resonance Testing (PCRT) is a non-destructive evaluation (NDE) method involving the collection and analysis of a part's resonance spectrum to characterize its material or damage state. Prior work used the finite element method (FEM) to develop forward modeling and model inversion techniques. In many cases, the inversion problem can become confounded by multiple parameters having similar effects on a part's resonance frequencies. To reduce the influence of confounding parameters and isolate the change in a part (e.g., creep), a part-to-itself (PTI) approach can be taken. A PTI approach involves inverting only the change in resonance frequencies from the before and after states of a part. This approach reduces the possible inversion parameters to only those that change in response to in-service loads and damage mechanisms. To evaluate the effectiveness of using a PTI inversion approach, creep strain and material properties were estimated in virtual and real samples using FEM inversion. Virtual and real dog bone samples composed of nickel-based superalloy Mar-M-247 were examined. Virtual samples were modeled with typically observed variations in material properties and dimensions. Creep modeling was verified with the collected resonance spectra from an incrementally crept physical sample. All samples were inverted against a model space that allowed for change in the creep damage state and the material properties but was blind to initial part dimensions. Results quantified the capabilities of PTI inversion in evaluating creep strain and material properties, as well as its sensitivity to confounding initial dimensions.

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.

Being Forward Not Backward: Lexical Limits to Masked Priming

ERIC Educational Resources Information Center

Davis, Chris; Kim, Jeesun; Forster, Kenneth I.

2008-01-01

This study investigated whether masked priming is mediated by existing memory representations by determining whether nonwords targets would show repetition priming. To avoid the potential confound that nonword repetition priming would be obscured by a familiarity response bias, the standard lexical decision and naming tasks were modified to make…

Intergenerational Transmission of Neuropsychological Executive Functioning

ERIC Educational Resources Information Center

Jester, Jennifer M.; Nigg, Joel T.; Puttler, Leon I.; Long, Jeffrey C.; Fitzgerald, Hiram E.; Zucker, Robert A.

2009-01-01

Relationships between parent and child executive functioning were examined, controlling for the critical potential confound of IQ, in a family study involving 434 children (130 girls and 304 boys) and 376 parents from 204 community recruited families at high risk for the development of substance use disorder. Structural equation modeling found…

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Selecting Evaluation Comparison Groups: A Cluster Analytic Approach.

ERIC Educational Resources Information Center

Davis, Todd Mclin; McLean, James E.

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

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

ERIC Educational Resources Information Center

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

2015-01-01

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

APOC3, Coronary Disease, and Complexities of Mendelian Randomization

PubMed Central

Cohen, Jonathan C.; Stender, Stefan; Hobbs, Helen H.

2014-01-01

Two new studies report that triglyceride (TG)-lowering mutations in APOC3 reduce coronary heart disease (CHD) (Crosby et al., 2014; Jørgensen et al., 2014). Here, we explore limitations of using Mendelian randomization to evaluate CHD risk, including potential confounding by the widespread use of statin therapy. PMID:25185943

Reconsidering the Relationship between Alcohol and Lethal Violence

ERIC Educational Resources Information Center

Phillips, Scott; Matusko, Jacqueline; Tomasovic, Elizabeth

2007-01-01

Prior event-based research regarding the relationship between alcohol and violence suffers from important limitations, including the absence of a comparison group, an inappropriate comparison group, or a comparison group that could be considered appropriate but does not control for potential confounders. To overcome such limitations, we use a…

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

ERIC Educational Resources Information Center

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

2006-01-01

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

Sampling depth confounds soil acidification outcomes

USDA-ARS?s Scientific Manuscript database

In the northern Great Plains (NGP) of North America, surface sampling depths of 0-15 or 0-20 cm are suggested for testing soil characteristics such as pH. However, acidification is often most pronounced near the soil surface. Thus, sampling deeper can potentially dilute (increase) pH measurements an...

Measuring Systematic Long-Term Trajectories of School Effectiveness Improvement

ERIC Educational Resources Information Center

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

2016-01-01

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

Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey.

PubMed

Robertson, Tony; Beveridge, Gayle; Bromley, Catherine

2017-01-01

Allostatic load is a multiple biomarker measure of physiological 'wear and tear' that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological 'health') was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death.

Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey

PubMed Central

Beveridge, Gayle; Bromley, Catherine

2017-01-01

Allostatic load is a multiple biomarker measure of physiological ‘wear and tear’ that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological ‘health’) was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death. PMID:28813505

Loss of Rare Fish Species from Tropical Floodplain Food Webs Affects Community Structure and Ecosystem Multifunctionality in a Mesocosm Experiment

PubMed Central

Pendleton, Richard M.; Hoeinghaus, David J.; Gomes, Luiz C.; Agostinho, Angelo A.

2014-01-01

Experiments with realistic scenarios of species loss from multitrophic ecosystems may improve insight into how biodiversity affects ecosystem functioning. Using 1000 L mesocoms, we examined effects of nonrandom species loss on community structure and ecosystem functioning of experimental food webs based on multitrophic tropical floodplain lagoon ecosystems. Realistic biodiversity scenarios were developed based on long-term field surveys, and experimental assemblages replicated sequential loss of rare species which occurred across all trophic levels of these complex food webs. Response variables represented multiple components of ecosystem functioning, including nutrient cycling, primary and secondary production, organic matter accumulation and whole ecosystem metabolism. Species richness significantly affected ecosystem function, even after statistically controlling for potentially confounding factors such as total biomass and direct trophic interactions. Overall, loss of rare species was generally associated with lower nutrient concentrations, phytoplankton and zooplankton densities, and whole ecosystem metabolism when compared with more diverse assemblages. This pattern was also observed for overall ecosystem multifunctionality, a combined metric representing the ability of an ecosystem to simultaneously maintain multiple functions. One key exception was attributed to time-dependent effects of intraguild predation, which initially increased values for most ecosystem response variables, but resulted in decreases over time likely due to reduced nutrient remineralization by surviving predators. At the same time, loss of species did not result in strong trophic cascades, possibly a result of compensation and complexity of these multitrophic ecosystems along with a dominance of bottom-up effects. Our results indicate that although rare species may comprise minor components of communities, their loss can have profound ecosystem consequences across multiple trophic levels due to a combination of direct and indirect effects in diverse multitrophic ecosystems. PMID:24416246

Quantification of multiple simultaneously occurring nitrogen flows in the euphotic ocean

NASA Astrophysics Data System (ADS)

Xu, Min Nina; Wu, Yanhua; Zheng, Li Wei; Zheng, Zhenzhen; Zhao, Huade; Laws, Edward A.; Kao, Shuh-Ji

2017-03-01

The general features of the N cycle in the sunlit region of the ocean are well known, but methodological difficulties have previously confounded simultaneous quantification of transformation rates among the many different forms of N, e.g., ammonium (NH4+), nitrite (NO2-), nitrate (NO3-), and particulate/dissolved organic nitrogen (PN/DON). However, recent advances in analytical methodology have made it possible to employ a convenient isotope labeling technique to quantify in situ fluxes among oft-measured nitrogen species within the euphotic zone. Addition of a single 15N-labeled NH4+ tracer and monitoring of the changes in the concentrations and isotopic compositions of the total dissolved nitrogen (TDN), PN, NH4+, NO2-, and NO3- pools allowed us to quantify the 15N and 14N fluxes simultaneously. Constraints expressing the balance of 15N and 14N fluxes between the different N pools were expressed in the form of simultaneous equations, the unique solution of which via matrix inversion yielded the relevant N fluxes, including rates of NH4+, NO2-, and NO3- uptake; ammonia oxidation; nitrite oxidation; DON release; and NH4+ uptake by bacteria. The matrix inversion methodology that we used was designed specifically to analyze the results of incubations under simulated in situ conditions in the euphotic zone. By taking into consideration simultaneous fluxes among multiple N pools, we minimized potential artifacts caused by non-targeted processes in traditional source-product methods. The proposed isotope matrix method facilitates post hoc analysis of data from on-deck incubation experiments and can be used to probe effects of environmental factors (e.g., pH, temperature, and light) on multiple processes under controlled conditions.

Cardiovascular disease and perceived weight, racial, and gender discrimination in U.S. adults.

PubMed

Udo, Tomoko; Grilo, Carlos M

2017-09-01

To date, most research on perceived discrimination and cardiovascular disease (CVD) has examined racial discrimination although other forms of discrimination may also impact physical and mental health. The current study investigated the relationship between three forms of discrimination (weight, race, and gender) and 3-year incidence of CVD in a large national sample of U.S. adults. 26,992 adults (55.5% women) who participated in the 2001-2002 and 2004-2005 National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) were included in this study. Multiple logistic regression analyses were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for three forms of perceived discrimination (simultaneously included in equations after adjusting for relevant potential confounds) for predicting CVD incidence at Wave 2. Perceived weight and racial discrimination were associated with significantly greater likelihood of reporting myocardial infarction (OR=2.56 [95% CI=1.31-4.98], OR=1.84 [95% CI=1.19-2.84], respectively) and minor heart conditions (OR=1.48 [95% CI=1.11-1.98], OR=1.41 [95% CI=1.18-1.70], respectively). Perceived racial discrimination was also significantly associated with greater likelihood of reporting arteriosclerosis (OR=1.61 [95% CI=1.11-2.34]). Odds ratios for diagnoses of arteriosclerosis, myocardial infarction, and other minor heart disease were largest for individuals reporting multiple forms of discrimination. Adults who experience weight and racial discrimination, and especially multiple forms of discrimination, may be at heightened risk for CVD. Perceived discrimination may be important to consider during assessment of life stressors by health providers. Future research should address the mechanisms that link discrimination and CVD to assist public health and policy efforts to reduce discrimination. Copyright © 2017. Published by Elsevier Inc.

The effect of single and multiple infections on atopy and wheezing in children.

PubMed

Alcantara-Neves, Neuza Maria; Veiga, Rafael Valente; Dattoli, Vitor Camilo Cavalcante; Fiaccone, Rosimeire Leovigildo; Esquivel, Renata; Cruz, Álvaro Augusto; Cooper, Philip John; Rodrigues, Laura Cunha; Barreto, Maurício Lima

2012-02-01

The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Association of Central Adiposity With Adverse Cardiac Mechanics: Findings From the Hypertension Genetic Epidemiology Network Study.

PubMed

Selvaraj, Senthil; Martinez, Eva E; Aguilar, Frank G; Kim, Kwang-Youn A; Peng, Jie; Sha, Jin; Irvin, Marguerite R; Lewis, Cora E; Hunt, Steven C; Arnett, Donna K; Shah, Sanjiv J

2016-06-01

Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s'] and early diastolic [e'] tissue velocities). We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m(2), waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s' velocity, and e' velocity (P<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics. © 2016 American Heart Association, Inc.

Increased risk of kidney damage among Chinese adults with simple renal cyst.

PubMed

Kong, Xianglei; Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Xu, Dongmei

2018-05-04

The presence of simple renal cyst (SRC) has been related to hypertension, the early and long-term allograft function, and aortic disease, but the relationship with kidney damage was still controversial. Accordingly, we conducted a large sample cross-sectional study to explore the association of SRC with indicators of kidney damage among Chinese adults. A total of 42,369 adults (aged 45.8 ± 13.67 years, 70.6% males) who visited the Health Checkup Clinic were consecutively enrolled. SRC was assessed by ultrasonography according to Bosniak category. Multiple regression models were applied to explore the relationships between SRC and indicators of kidney damage [proteinuria (dipstick urine protein ≥ 1+) and decreased estimated glomerular filtration rate (DeGFR) < 60 ml/min/1.73 m 2 ]. Among all participants in the study, the prevalence of SRC was 10.5%. As a categorical outcome, participants with more 1 cyst and with 1 cyst had higher percentage of proteinuria [53 (5.3%) and 93 (2.7%) vs. 596 (1.6%), p < 0.001] and DeGFR [57 (5.7%) and 85 (2.5%) vs. 278 (0.7%), p < 0.001] compared with participants with no cyst. SRC significantly correlated with proteinuria [OR 1.59 (95% CI 1.30-1.95)] and DeGFR [OR 1.97 (95% CI 1.56-2.47)] after adjusting for potential confounders. Furthermore, the results also demonstrated that maximum diameter (per 1 cm increase), bilateral location, and multiple cysts significantly correlated with DeGFR in the multiple logistic regression analysis. The study revealed that SRC significantly correlated with kidney damage and special attention should be paid among Chinese adults with SRC.

Effectiveness of a combination of ezetimibe and statins in patients with acute coronary syndrome and multiple comorbidities: A 6-year population-based cohort study.

PubMed

Lin Wu, Fe-Lin; Wang, Jui; Ho, Wei; Chou, Chia-Hung; Wu, Yi-Jung; Choo, Dan-Wei; Wang, Yu-Wen; Chen, Po-Yu; Chien, Kuo-Liong; Lin, Zhen-Fang

2017-04-15

The clinical benefits of a combination of statins and ezetimibe in patients with acute coronary syndrome (ACS) were observed in a clinical trial. However, little is known regarding the effectiveness of using statins with or without ezetimibe in patients with ACS and multiple comorbidities in real-world clinical practice. This is a nationwide population-based cohort study using Taiwan National Health Insurance Research Database. A total of 212,110 patients with ACS who had been discharged after their first ACS events between 2006 and 2010 were enrolled. A propensity score matching approach was used to create matched cohorts for adjusting potential confounders. Cox proportional hazards regressions were performed to estimate the risk of re-hospitalization for ACS and revascularization. Patients in the statins-plus-ezetimibe group had a significantly lower risk of re-hospitalization for ACS (adjusted hazard ratio [HR]=0.64, 95% confidence interval [CI]: 0.60-0.69) and revascularization (HR=0.69, 95% CI: 0.63-0.76) than those in the statins-alone group. In the statins-plus-ezetimibe group, female patients had a lower risk of re-hospitalization for ACS than male patients did, and patients without diabetes mellitus had a lower risk of re-hospitalization for ACS than did patients with diabetes mellitus. Patients with ACS and multiple comorbidities receiving a combination therapy of statins and ezetimibe had a lower risk of re-hospitalization for ACS and revascularization than those receiving statins alone. Significant interaction effects were observed between combination with ezetimibe, sex, and diabetes mellitus. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

PubMed

Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

2012-07-18

Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.