Exposure Covariates Research Articles

A scoping review of Table 2 fallacy in the oral health literature.

Coined by Westreich and Greenland in 2013, Table 2 fallacy refers to the practice of reporting estimates of the primary exposure and adjustment covariates derived from a single model on the same table. This study seeks to describe the extent to which Table 2 fallacy is present in the oral health literature and provide recommendations on presenting findings from multivariable-adjusted models and/or interpretation of adjustment covariate estimates that are not the primary exposure. We conducted a scoping review in PubMed and Scopus of human observational studies published in 4 oral health journals (JDR-CTR, CDOE, JPHD, BMC Oral Health) starting in 2013 until the end of 2018. The resulting articles were exported into Excel and were either included or excluded for full-text review based on six criteria. After categorizing the articles, we exported and summarized the results in SAS. A total of 1358 articles were initially screened of which 937 articles were excluded based on title or abstract for being animal studies, systematic reviews or meta-analysis, prediction models or descriptive studies. The remaining 421 articles were eligible for full text reviewed of which, 189 (45%) committed Table 2 fallacy. The prevalence of table 2 fallacy appears high in the oral health literature. The problem of presenting multiple effect estimates derived from a single model in the same table is that it inadvertently encourages the reader to interpret all estimates the same way, often as total effects. Implications and recommendations are discussed.

Hidradenitis suppurativa is associated with hypothyroidism and hyperthyroidism: a large-scale population-based study.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving the skin bearing apocrine glands. There are numerous comorbidities and associated diseases among patients with HS. The association of HS and thyroid abnormalities is equivocal. We aimed to explore whether HS is associated with thyroid disorders. In this cross-sectional large-scale population-based study in Israel, patients with a validated diagnosis of HS were matched at a proportion of 1:5 with age- and gender-matched healthy controls without HS. A cross-checking for HS diagnosis by International Classification of Diseases, ninth revision (ICD-9) coding, and hyperthyroidism and hypothyroidism by ICD-9 coding was performed. Demographic and exposure covariates were identified. Univariate and multivariate logistic regressions were utilized to establish the association of HS with thyroid disorders. Study participants included 4,191 HS patients and 20,941 controls. The average age of patients was 39.7years old, and 61.8% were female. 53.4% of HS patients and 13.5% of controls (P<0.001) were smokers. Odds ratios (ORs) for hypothyroidism and hyperthyroidism in HS were 2.91 (95% confidence interval [CI] 2.48-3.40) and 2.25 (95% CI 1.55-3.28), respectively (P<0.001 for both). While the association of HS with hypothyroidism was maintained across genders and all age groups, and remained positive after controlling for smoking status, the association with hyperthyroidism remained positive only among females, middle-aged patients, and nonsmokers. HS is independently associated with hypothyroidism. The association of HS with hyperthyroidism held significance only in limited subgroups. Smoking status is a major modifier, mainly in the association of HS with hyperthyroidism.

Bayesian Profile Regression to Deal With Multiple Highly Correlated Exposures and a Censored Survival Outcome. First Application in Ionizing Radiation Epidemiology.

As multifactorial and chronic diseases, cancers are among these pathologies for which the exposome concept is essential to gain more insight into the associated etiology and, ultimately, lead to better primary prevention strategies for public health. Indeed, cancers result from the combined influence of many genetic, environmental and behavioral stressors that may occur simultaneously and interact. It is thus important to properly account for multifactorial exposure patterns when estimating specific cancer risks at individual or population level. Nevertheless, the risk factors, especially environmental, are still too often considered in isolation in epidemiological studies. Moreover, major statistical difficulties occur when exposures to several factors are highly correlated due, for instance, to common sources shared by several pollutants. Suitable statistical methods must then be used to deal with these multicollinearity issues. In this work, we focused on the specific problem of estimating a disease risk from highly correlated environmental exposure covariates and a censored survival outcome. We extended Bayesian profile regression mixture (PRM) models to this context by assuming an instantaneous excess hazard ratio disease sub-model. The proposed hierarchical model incorporates an underlying truncated Dirichlet process mixture as an attribution sub-model. A specific adaptive Metropolis-Within-Gibbs algorithm—including label switching moves—was implemented to infer the model. This allows simultaneously clustering individuals with similar risks and similar exposure characteristics and estimating the associated risk for each group. Our Bayesian PRM model was applied to the estimation of the risk of death by lung cancer in a cohort of French uranium miners who were chronically and occupationally exposed to multiple and correlated sources of ionizing radiation. Several groups of uranium miners with high risk and low risk of death by lung cancer were identified and characterized by specific exposure profiles. Interestingly, our case study illustrates a limit of MCMC algorithms to fit full Bayesian PRM models even if the updating schemes for the cluster labels incorporate label-switching moves. Then, although this paper shows that Bayesian PRM models are promising tools for exposome research, it also opens new avenues for methodological research in this class of probabilistic models.

Long-term air pollution exposure and incident dementia in older adults in the Gingko Evaluation of Memory Study

Introduction: Air pollution is associated with reduced cognitive performance and accelerated cognitive decline in older adults. Less is known regarding air pollution’s contribution to all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD). Methods: Over 3,000 adults aged 75 years and older residing in four communities in the United States participated in the Ginkgo Evaluation of Memory Study (GEMS) between 2000-2008. Rigorous evaluations of dementia occurred every six months, and cases were identified by expert panel based on neuropsychological battery, neurological examination, and magnetic resonance imaging results. Fine particulate matter (PM2.5) concentrations were predicted from a spatiotemporal model incorporating land-use regression and spatial smoothing approaches. Estimates were based on residential address histories obtained up to twenty years prior to study entry using the commercially available LexisNexis database. Cox models adjusted for age and date of randomization, site, gender, treatment assignment, education, smoking, and zip code level income were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Mean follow-up time was 5.7 years for the 2,511 GEMS participants free of mild cognitive impairment and dementia at study entry who had information on exposure, dementia status, and relevant covariates. An approximate interquartile range (2 µg/m3) increase in mean PM2.5 exposure twenty years prior to study entry was associated with a 19% greater risk of all-cause dementia (HR: 1.19; 95% CI: 1.03, 1.37) in adjusted analyses. Risks appeared stronger for VaD and mixed VaD/AD (HR: 1.25; 95% CI: 0.96, 1.62) than for AD only (HR: 1.15; 95% CI: 0.97, 1.37). Conclusions: Preliminary results indicate a strong association between air pollution exposure and all-cause dementia and that PM2.5 exposure may be particularly important in dementia with vascular features. Findings provide evidence that air pollution exposure reductions may be a key target for reducing the burden of dementia in older adults.

Development and Validation of a Model to Predict Neonatal Abstinence Syndrome

To develop and validate clinical risk prediction tools for neonatal abstinence syndrome (NAS). We developed prediction models for NAS based on a set of 30 demographic and antenatal exposure covariates collected during pregnancy. Data (outpatient prescription, vital, and administrative records), were obtained from enrollees in the Tennessee Medicaid Program from 2009 to 2014. Models were created using logistic regression and backward selection based on improvement in the Akaike information criterion, and internally validated using bootstrap cross-validation. A total of 218 020 maternal and infant dyads met inclusion criteria, of whom 3208 infants were diagnosed with NAS. The general population model included age, hepatitis C virus infection, days of opioid used by type, number of cigarettes used daily, and the following medications used in the last 30day of pregnancy: bupropion, antinausea medicines, benzodiazepines, antipsychotics, and gabapentin. Infant characteristics included birthweight, small for gestational age, and infant sex. A high-risk model used a smaller number of predictive variables. Both models discriminated well with an area under the curve of 0.89 and were well-calibrated for low-risk infants. We developed 2 predictive models for NAS based on demographics and antenatal exposure during the last 30days of pregnancy that were able to risk stratify infants at risk of developing the syndrome.

Liraglutide pharmacokinetics and exposure-response in pediatric patients with type 2 diabetes.

Objectives Based on the ellipse trial, liraglutide was recently approved for use in pediatric patients with type 2 diabetes. We report the comparative exposure of liraglutide in pediatric vs. adult patients. Methods In this pharmacokinetic (PK) and exposure-response meta-analysis, data from two pediatric trials (including ellipse) and two adult trials of liraglutide were compiled (1,137 PK observations from 116 patients) to determine the impact of body weight, age and sex on liraglutide exposure. The exposure-response relationship for glycated hemoglobin (HbA1c) and body weight was compared between pediatric and adult patients. Additionally, the relationships between exposure and change from baseline in body mass index (BMI) and BMI standard deviation score (SDS) were assessed. Results The same liraglutide dose showed comparable exposure levels in pediatric and adult patients. Body weight and sex were the most important covariates for liraglutide exposure. There was an increasing response with higher liraglutide concentrations, and greater reductions were observed from baseline in HbA1c at 26weeks vs. placebo. A trend toward lower body weight, BMI and BMI SDS was observed at 26weeks. Conclusions These results support use of the same liraglutide dosing regimen in children and adolescents, aged≥10 years, as that used in adults.

413 Wildfire-associated air pollution impacts clinic visits for itch and atopic dermatitis

With climate change, the frequency and intensity of wildfires are expected to increase, leading to episodes of poor air quality that could exacerbate patients’ pre-existing dermatoses. To assess the effects of exposure to wildfire-associated air pollution on skin, we investigated if the 2018 California Camp Fire led to detectable increases in clinic visits for atopic dermatitis (AD) or itch at dermatology clinics 175 miles from the origin of the fire. We collected data from 2015-2019 on particulate matter (PM2.5) concentration and smoke plume density in San Francisco and the number of outpatient dermatology visits for AD or itch symptoms at an academic medical center. Data were analyzed using Poisson regression with empirical standard errors, and the models included exposure lags and covariates: patient age and sex, temperature, and humidity. We found that the rates of weekly pediatric AD clinic visits, adult AD clinic visits, and pediatric itch symptoms during the Camp Fire were respectively 1.75 (95% CI: 1.21, 2.50), 1.28 (1.08, 1.51), and 2.10 (1.44, 3.00) times the rate for non-fire weeks for a 0-week lag, adjusted for time of year and confounders. Every 10 μg/m3 increase in average weekly PM2.5 concentration was associated with an adjusted rate ratio of 1.08 (95% CI: 1.04, 1.12) for weekly pediatric AD clinic visits. Thus, there was increased use of dermatology services for AD associated with exposure to air pollution from the Camp Fire, particularly for the pediatric population. With an impaired skin barrier function, AD patients may be at increased risk of adverse skin reactions following pollution exposure, which can negatively impact quality of life. Understanding the effects of air pollution on patients’ skin health can inform how dermatologists counsel patients and expand comprehension of the broader health effects of climate change.

Are anti-smoking social norms associated with tobacco control mass media campaigns, tax and policy changes? Findings from an Australian serial cross-sectional population study of smokers

BackgroundAnti-smoking social norms are associated with subsequent quitting behaviours. We examined if exposure to tobacco control advertisements and policy changes predict subjective (perceived disapproval of smoking among close family and...

Retrospective Identification of Bacterial Isolates From Emergency Laparotomy Surgical Site Infections in Horses

Surgical site infection (SSI) with multiresistant bacteria is an important cause of postoperative morbidity after laparotomy in horses. The objective of this study was to identify bacteria isolates and their antibiotic resistance patterns associated with the development of wound infection in horses after laparotomy. This is a retrospective case series. Medical records of horses that underwent ventral midline exploratory laparotomy in a four-year period at one equine hospital were reviewed. Results of microbiologic culture and susceptibility testing are described. The study group consisted of 183 (100%) horses that recovered from anesthesia after laparotomy. The prevalence of infection was 19% (24/124) after first surgery and 83% (19/23) after relaparotomy. The most common microbial isolates were bacteria of the family Enterobacteriaceae followed by Staphylococcus ssp., Enterococcus ssp., Streptococcus ssp., and Bacteroides ssp. Bacteria from the family Enterobacteriaceae showed the lowest resistance to amphenicols, cephalosporins, and quinolones groups of antibiotics. Coagulase-positive Staphylococci were sensitive to amphenicols and only 33% were resistant to trimethoprim/sulfamethoxazole. The most commonly used perioperative and postoperative antibiotics were gentamicin and amoxicillin. Limitations include poor control over exposure factors, covariates, and potential confounders during the surgery, recovery time, or period of hospitalization; relying on others for accurate outcome assessment and recordkeeping; lack of follow-up information once animals were discharged from the hospital. Despite 5 days of antibiotic prophylaxis, the rate of incisional infection is still high. The most common isolates from SSI belong to the family Enterobacteriaceae and the genus Staphylococcus, which showed high resistance to the antibiotics used before the gastrointestinal surgery.

Population Pharmacokinetics of Total and Free Erdafitinib in Adult Healthy Volunteers and Cancer Patients: Analysis of Phase 1 and Phase 2 Studies.

A population pharmacokinetic (PK) model was developed using data pooled from 6 clinical studies (3 in healthy volunteers and 3 in cancer patients) to characterize total and free plasma concentrations of erdafitinib following single- and multiple-dose administration, to understand clinically relevant covariates, and to quantify the inter- and intraindividual variability in erdafitinib PK. An open, linear, 3-compartment disposition model with first-order absorption and a lag time was used to describe the PK profile of total and free erdafitinib plasma concentrations. The PK of erdafitinib were linear and time independent. After oral administration, erdafitinib was rapidly absorbed, with a time to maximum concentration between 2 and 4 hours. In patients, erdafitinib total apparent oral clearance was 0.200L/h (median free fraction=0.24%), and the effective terminal half-life of total drug was 76.4 hours. Interindividual variability in PK parameters was moderate for oral clearance and central volume of distribution, and large for absorption rate and peripheral volume of distribution. Sex and renal function were significant covariates on free oral clearance, while weight, sex, and α1 -acid-glycoprotein were significant on oral central volume of distribution. Age, race, and mild hepatic impairment were not significant covariates of erdafitinib exposure. Given that the magnitude of the covariate effects were within 25% of reference values and that the recommended dosing regimen of erdafitinib comprises individual dose up-titrations and reductions based on presence or absence of toxicities, the clinical relevance of the investigated covariates is expected to be limited, and no dose adjustments are warranted.

Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder

ObjectiveTo compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). MethodsThe IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus “No drug”. ResultsThe annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to “No drug”. A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed. ConclusionsThere is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.

Gender differences in exposure to potentially traumatic events and diagnosis of posttraumatic stress disorder (PTSD) by racial and ethnic group

ObjectiveThere is a robust literature base documenting gender differences and racial/ethnic differences in exposure to potentially traumatic events (PTEs) and posttraumatic stress disorder (PTSD) diagnosis. Yet, to the best of our knowledge, this is the first study to evaluate the risk of PTEs and PTSD between genders, stratified by race/ethnicity. We aimed to better understand whether factors associated with poor psychological adjustment following PTEs (e.g., PTE type, sociodemographic factors, social support) varied by gender and race/ethnicity. MethodData were collected from three U.S.-based national studies comprising the Collaborative Psychiatric Epidemiologic Surveys (CPES; N = 13,649). Trained lay interviewers administered questionnaires and collected data on PTE exposure, PTSD, and psychosocial covariates. Regression analyses were conducted to investigate relations between PTEs, PTSD, and gender, stratified by race/ethnicity. ResultsAdjusting for sociodemographic variables, mental health comorbidity, social support, and PTE frequency, White, African-American, and Afro-Caribbean women had higher odds of PTSD than men in their respective racial/ethnic groups, whereas gender differences were not observed for Latinos or Asians. ConclusionFindings suggest that risk of exposure to PTEs and PTSD may differ by gender and race/ethnicity. Future studies should consider the contributions of social, cultural, and contextual factors in estimating PTSD risk.

Prenatal air pollution and early childhood asthma

PDS 68: Outdoor air pollution, mortality and morbidity, Exhibition Hall (PDS), Ground floor, August 26, 2019, 10:30 AM - 12:00 PM Background: Prior studies suggest that prenatal air pollution may perturb normal fetal lung development and contribute to risk of child asthma, but few have had opportunity to investigate developmental windows of susceptibility or have been limited in exposure assessment or covariate adjustment. Methods: Our study population included participants in two pregnancy cohorts within the ECHO-PATHWAYS consortium, CANDLE (births in 2007-2011) in Memphis, TN and TIDES (births in 2011-2013) in Seattle, WA; San Francisco, CA; and Minneapolis, MN, who had term births (37+ weeks). Child asthma was defined based on parent-report of ever asthma. Exposure to ambient fine particulate matter (PM2.5) during prenatal phases of fetal lung development was estimated using a spatiotemporal model. We used Poisson regression and adjusted for city, child sex, year and season of birth, maternal race, education, asthma, age at delivery, prior live births, pre-pregnancy body mass index, prenatal smoking, child’s postnatal secondhand smoke exposure, pets in the child’s home, and neighborhood-level socioeconomic status. Results: Children (n=1334) were on average 4.3 years old (standard deviation [SD] 0.5), 49% male, and 11.6% had ever asthma; 46% of mothers were black and 54% had a college/technical school degree. City-specific mean PM2.5 exposures averaged across the prenatal period ranged from 5.2 µg/m3 (SD 0.9) to 10.6 µg/m3 (SD 1.0). A 2 µg/m3 higher PM2.5 exposure during the saccular phase (week 24 to week 36 of pregnancy) was associated with 28% higher risk of asthma (95% confidence interval [CI]: 1.00, 1.64; p=0.055). This effect was larger in boys than in girls, though interaction was not statistically significant. Higher average exposure across all of pregnancy was not associated with asthma (risk ratio 1.06, 95% CI: 0.84, 1.35). Conclusions: Preliminary results suggest that the later phases of prenatal lung development may be particularly sensitive to the developmental toxicity of PM2.5.

The CHEAR Data Repository

TPS 691: Methods of measurement, design and data analysis, Exhibition Hall, Ground floor, August 28, 2019, 3:00 PM - 4:30 PM Funded by the U.S. National Institute of Environmental Health Sciences, the Children’s Health Exposure Analysis Resource (CHEAR) provides scientific investigators access to laboratory and statistical analyses aimed at incorporating and expanding environmental exposures within their research. To benefit the broader research community, the CHEAR Data Center has created a public data repository that houses deidentified data from studies accepted into the CHEAR program. To date, 26 studies have submitted data containing > 41,000 specimens, > 3,000 mothers and children and 139 environmental chemicals. The goal of this repository is to promote the secondary analysis of pooled CHEAR studies by providing data in a manner that is findable, accessible, interoperable and reusable (FAIR). The repository has been constructed by coupling the open-source Human-aware Data Acquisition Framework with semantic annotation templates that transform CHEAR datasets into machine-readable knowledge graphs. These tools facilitate the ingestion, semantic-mapping, harmonization and accessibility of data (epidemiologic, clinical and biomarker) and metadata across the multiple studies within the CHEAR Program. We demonstrate how users of the public repository have the ability to simultaneously search, view, and download data from multiple CHEAR studies. The repository can be searched based on a number of factors including health outcomes, biological markers of exposure and common covariates. Because data have been harmonized to a common vocabulary (the CHEAR ontology), downloaded datasets automatically contain CHEAR-wide harmonized codes and labels for variables that are present in multiple studies. By selecting common data elements, users can create customized datasets with accompanying codebooks in a format that is easily imported into statistical analysis software. For maximal FAIR impact, we have promoted the CHEAR data, tools and methods through Google dataset search, Github, and Bioportal. The repository will encourage secondary analysis of pooled CHEAR studies, facilitating investigations that leverage larger sample sizes and greater exposure variability.

Gender Differences in Youth Exposure to Community Violence: A Partial Test of Power-Control Theory

Youths’ exposure to community violence increases their risk for harmful emotional and behavioral outcomes. Several family management strategies protect youth against exposure though there is scant literature exploring whether their application is gendered. Using data from the Project on Human Development in Chicago Neighborhoods, we draw from power-control theory to assess gender differences in family management strategies and the extent to which this accounts for boys’ greater exposure to neighborhood violence. Controlling for neighborhood contextual factors and youth covariates of exposure to violence, findings suggest that parents adopt gendered parenting practices, which in turn helps clarify why boys are more likely to report exposure to community violence.

Alcohol Use in Pregnancy and Miscarriage: A Systematic Review and Meta-Analysis.

To systematically review and critically evaluate studies reporting alcohol exposure during pregnancy and miscarriage. We searched PubMed, EMBASE, PsycINFO, and ProQuest Theses for publications from January 1970 to January 2019. We identified studies about alcohol exposure during pregnancy and miscarriage. Information about study population, alcohol exposure assessment, outcome definition, covariates, and measures of association was collected. We assessed study quality using an adapted Newcastle-Ottawa Scale. Data were abstracted by 2 investigators independently. We conducted a random-effects meta-analysis to calculate the association between alcohol exposure and miscarriage risk and performed subgroup analyses to determine robustness of results to study differences. For studies reporting dose-specific effects, a pooled dose-response association was estimated using generalized least squares regression with and without restricted cubic spline terms for number of drinks consumed per week. Of 2,164 articles identified, 24 were eligible for inclusion. Meta-analysis of data from 231,808 pregnant women finds those exposed to alcohol during pregnancy have a greater risk of miscarriage compared to those who abstained (odds ratio [OR] 1.19, 95% confidence intervals [CI] 1.12, 1.28). Estimates did not vary by study design, study country, or method of alcohol ascertainment. For alcohol use of 5 or fewer drinks per week, each additional drink per week was associated with a 6% increase in miscarriage risk (OR 1.06, 95% CI 1.01, 1.10). Common study limitations reflect challenges inherent to this research, including difficulty recruiting participants early enough in pregnancy to observe miscarriage and collecting and quantifying information about alcohol consumption during pregnancy that accurately reflects use. This review provides evidence that alcohol consumption during pregnancy is associated with a dose-mediated increase in miscarriage risk. Future studies evaluating change in alcohol use in pregnancy are needed to provide insight into how alcohol consumption prior to pregnancy recognition impacts risk.

Jet fuel exposure and auditory outcomes in Australian air force personnel

BackgroundAnimal data suggest that jet fuels such as JP-8 are associated with hearing deficits when combined with noise and that the effect is more pronounced than with noise exposure alone. Some studies suggest peripheral dysfunction while others suggest central auditory dysfunction. Human data are limited in this regard. The aim of this study was to investigate the possible chronic adverse effects of JP-8 combined with noise exposure on the peripheral and central auditory systems in humans.MethodsFifty-seven participants who were current personnel from the Royal Australian Air Force were selected. Based on their levels of exposure to jet fuels, participants were divided into three exposure groups (low, moderate, high). Groups were also categorised based on their noise exposure levels (low, moderate, high). All participants were evaluated by tympanometry, pure-tone audiometry (1–12 kHz), distortion product otoacoustic emissions (DPOAEs), auditory brainstem response (ABR), words-in-noise, compressed speech, dichotic digit test, pitch pattern sequence test, duration pattern sequence test and adaptive test of temporal resolution. All auditory tests were carried out after the participants were away from the Air Force base for a minimum of two weeks, thus two weeks without jet fuel and noise exposure.ResultsJet fuel exposure was significantly associated with hearing thresholds at 4 and 8 kHz; average hearing thresholds across frequencies in the better ear; DPOAEs at 2.8, 4 and 6 kHz; ABR wave V latency in the right ear; compressed speech and words-in-noise. Further analyses revealed that participants with low exposure level to jet fuels showed significantly better results for the aforementioned procedures than participants with moderate and high exposure levels. All results were controlled for the covariates of age and noise exposure levels.ConclusionsThe results suggest that jet fuel exposure, when combined with noise exposure, has an adverse effect on audibility in humans. Taking all the test results into consideration, jet fuel exposure combined with noise exposure specifically seems to affect the peripheral hearing system in humans.

Weighted estimation for multivariate shared frailty models for complex surveys.

Multivariate frailty models have been used for clustered survival data to characterize the relationship between the hazard of correlated failures/events and exposure variables and covariates. However, these models can introduce serious biases of the estimation for failures from complex surveys that may depend on the sampling design (informative or noninformative). In order to consistently estimate parameters, this paper considers weighting the multivariate frailty model by the inverse of the probability of selection at each stage of sampling. This follows the principle of the pseudolikelihood approach. The estimation is carried out by maximizing the penalized partial and marginal pseudolikelihood functions. The performance of the proposed estimator is assessed through a Monte Carlo simulation study and the 4 waves of data from the 1998-1999 Early Childhood Longitudinal Study. Results show that the weighted estimator is consistent and approximately unbiased.

Comparison of 71 bipolar disorder pharmacotherapies for kidney disorder risk: The potential hazards of polypharmacy

Background: This study compared the largest set of bipolar disorder pharmacotherapies to date (71 drugs and drug combinations) for risk of kidney disorders (KDs). Methods: This retrospective observational study used the IBM MarketScan® database to analyze data on 591,052 adults with bipolar disorder without prior nephropathy, for onset of KDs (of “moderate” or “high” severity) following psychopharmacotherapy (lithium, mood stabilizing anticonvulsants [MSAs], antipsychotics, antidepressants), or “No drug”. Cox regression models included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus “No drug”. Results: Newly observed KD occurred in 14,713 patients. No regimen had significantly lower risk of KDs than “No drug”. The HR estimates ranged 0.86–2.66 for “all” KDs and 0.87–5.30 for “severe” KDs. As additional drugs were combined to compare more complex polypharmacies, higher HRs were consistently observed. Most regimens containing lithium, MSAs, or antipsychotics had a higher risk than “No drug” (p < 0.05). The risk for “all” and “severe” KDs was highest respectively on monoamine oxidase inhibitors (MAOIs) (HR = 2.66, p = 5.73 × 10−5), and a lithium-containing four-class combination (HR = 5.30, p = 2.46 × 10−9). The HR for lithium monotherapy was 1.82 (p = 4.73 × 10−17) for “severe” KDs. Limitations: The limitations inherent for an observational study were non-randomized assignment of patients to treatment groups, non-standardization of diagnostic decisions, and non-uniform quality of data collection. No correction was made for medication dosage. Conclusions: The findings support literature concerns about lithium nephrotoxicity and highlight the potential risks of MAOIs, MSAs, antipsychotics and psychotropic polypharmacy.

Heavy metals, welding fumes, and other occupational exposures, and the risk of kidney cancer: A population-based nested case-control study in three Nordic countries

ObjectivesTo determine whether occupational exposure to heavy metals (chromium (VI), iron, nickel, lead) and welding fumes is associated with the risk of kidney cancer and to describe whether other occupational exposures included in the Job Exposure Matrix of the Nordic Occupational Cancer (NOCCA) study are associated with the risk. Materials and methodsNested case-control study among individuals registered in population censuses in Finland, Iceland, and Sweden in 1960–1990. A total of 59,778 kidney cancer cases, and 298,890 controls matched on sex, age, and country. Cumulative occupational exposures to metals (chromium (VI), iron, nickel, lead), welding fumes, and 24 other occupational exposure covariates, lagged 0, 10, and 20 years. ResultsOverall, there was no or very little association between kidney cancer and exposures studied. The risk was elevated in individuals with high exposure to asbestos (OR 1.19, 95%CI 1.08–1.31). The risk was significantly decreased for individuals characterized with high perceived physical workload (OR 0.86, 95%CI 0.82–0.91), high exposure to ultraviolet radiation (OR 0.85, 95%CI 0.79–0.92), and high exposure to wood dust (OR 0.82, 95%CI 0.71–0.94). The risk of kidney cancer under the age of 59 was elevated in individuals with high exposure to nickel (OR 1.49, 95%CI 1.03–2.17). The risk of kidney cancer in age 59–74 years was elevated for individuals with high exposure to iron (OR 1.41, 95%CI 1.07–1.85), and high exposure to welding fumes (OR 1.43, 95%CI 1.09–1.89). ConclusionsThe only markedly elevated risks of kidney cancer were seen for the highest exposures of nickel and iron/welding fumes in specific age strata.