Faculty Bibliography

BACKGROUND:Arsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations. OBJECTIVES/OBJECTIVE:We investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418). METHODS:Associations between toenail As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models. RESULTS:Covariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2). Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15-F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a 2.98% decrease in 15-F2t-IsoP [(95% CI: -6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3% decrease (95% CI: -4.3, -0.3) in MMP-9, and a 5% increase in %uMMA was associated with a 7.7% decrease (95% CI: -12.6, -2.5) in PAI-1. CONCLUSION/CONCLUSIONS:In a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062.

BACKGROUND:Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis. RESULTS:). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8). CONCLUSIONS:Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.

BACKGROUND:Screening and brief intervention (SBI) for unhealthy drinking has not been widely implemented in primary care partly due to reliance on physicians to perform it. METHODS:We implemented a model of nursing staff-delivered SBI for unhealthy drinking for adult patients receiving primary care at an academically-affiliated Federally Qualified Health Center in the Bronx, NY. Our model consisted of nursing staff screening all patients with the alcohol use disorders identification test consumption questions (AUDIT-C) and, if screening positive, providing BI or referral to specialty services. We developed a clinical decision support tool integrated into the electronic health record to guide nursing staff and record SBI provision. To evaluate this model, we determined overall SBI delivery to patients and factors associated with receiving SBI. RESULTS:Between October 2013 and September 2014, 9119 unique adult patients made 24,285 visits. Patients were majority women (67.5%) and Hispanic/Latino (54.5%). Overall, 46.2% were screened, with 19.0-35.8% of eligible patients screened in each month. Increasing age (OR: 0.82 [95% CI 0.80-0.85] for a 10-year increase), female sex (OR: 0.83 [95% CI 0.77-0.91]), and chronic conditions like hypertension (OR: 0.62 [95% CI 0.56-0.70]) and diabetes (OR: 0.66 [95% CI 0.58-0.75]), among others, were associated with a lower odds of being screened. Of all patients screened, 225 (5.3%) screened positive and of those patients, 122 (54.2%) received a BI. Patients with higher AUDIT-C scores were more likely to receive a BI (OR: 1.24 [95% CI 1.04-1.47] for a 1-point increase) and non-English speaking patients were less likely to receive a BI than those who spoke English (OR: 0.42 [95% CI 0.18-0.97]). CONCLUSIONS:Our model of SBI resulted in screening of nearly half of all eligible patients and BI provision to over half of those screening positive. Future efforts to improve SBI delivery should focus on groups such as older adults, women, and those with chronic medical conditions.

OBJECTIVE:Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical (hospital) surveillance in Nigeria. RESULTS:Children were selected via convenience sampling from communities and a tertiary care center (n = 91) during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority (79.1%) of subjects were under 6 years old, of whom 46 were infected (63.9%). A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% (15/16) of clinical subjects, and 6.7% (5/75) of community subjects (significant difference, p < 0.001). Coronavirus OC43 was the most common virus detected in community members (13.3%, 10/75). A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic (2/16) and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of respiratory infections.

AIMS/OBJECTIVE:Sudden cardiac death (SCD) is a major public health burden. Mitochondrial dysfunction has been implicated in a wide range of cardiovascular diseases including cardiomyopathy, heart failure, and arrhythmias, but it is unknown if it also contributes to SCD risk. We sought to examine the prospective association between mtDNA copy number (mtDNA-CN), a surrogate marker of mitochondrial function, and SCD risk. METHODS AND RESULTS/RESULTS:We measured baseline mtDNA-CN in 11 093 participants from the Atherosclerosis Risk in Communities (ARIC) study. mtDNA copy number was calculated from probe intensities of mitochondrial single nucleotide polymorphisms (SNP) on the Affymetrix Genome-Wide Human SNP Array 6.0. Sudden cardiac death was defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual without evidence of a non-cardiac cause of cardiac arrest. Sudden cardiac death cases were reviewed and adjudicated by an expert committee. During a median follow-up of 20.4 years, we observed 361 SCD cases. After adjusting for age, race, sex, and centre, the hazard ratio for SCD comparing the 1st to the 5th quintiles of mtDNA-CN was 2.24 (95% confidence interval 1.58-3.19; P-trend <0.001). When further adjusting for traditional cardiovascular disease risk factors, prevalent coronary heart disease, heart rate, QT interval, and QRS duration, the association remained statistically significant. Spline regression models showed that the association was approximately linear over the range of mtDNA-CN values. No apparent interaction by race or by sex was detected. CONCLUSION/CONCLUSIONS:In this community-based prospective study, mtDNA-CN in peripheral blood was inversely associated with the risk of SCD.

BACKGROUND:A common belief is that one quarter to one third of all diabetes cases remain undiagnosed. However, such prevalence estimates may be overstated by epidemiologic studies that do not use confirmatory testing, as recommended by clinical diagnostic criteria. OBJECTIVE:To provide national estimates of undiagnosed diabetes by using a confirmatory testing strategy, in line with clinical practice guidelines. DESIGN/METHODS:Cross-sectional study. SETTING/METHODS:National Health and Nutrition Examination Survey results from 1988 to 1994 and 1999 to 2014. PARTICIPANTS/METHODS:U.S. adults aged 20 years and older. MEASUREMENTS/METHODS:Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (≥7.0 mmol/L [≥126 mg/dL]) and hemoglobin A1c (≥6.5%) in persons without diagnosed diabetes. RESULTS:The prevalence of total (diagnosed plus confirmed undiagnosed) diabetes increased from 5.5% (9.7 million adults) in 1988 to 1994 to 10.8% (25.5 million adults) in 2011 to 2014. Confirmed undiagnosed diabetes increased during the past 2 decades (from 0.89% in 1988 to 1994 to 1.2% in 2011 to 2014) but has decreased over time as a proportion of total diabetes cases. In 1988 to 1994, the percentage of total diabetes cases that were undiagnosed was 16.3%; by 2011 to 2014, this estimate had decreased to 10.9%. Undiagnosed diabetes was more common in overweight or obese adults, older adults, racial/ethnic minorities (including Asian Americans), and persons lacking health insurance or access to health care. LIMITATION/CONCLUSIONS:Cross-sectional design. CONCLUSION/CONCLUSIONS:Establishing the burden of undiagnosed diabetes is critical to monitoring public health efforts related to screening and diagnosis. When a confirmatory definition is used, undiagnosed diabetes is a relatively small fraction of the total diabetes population; most U.S. adults with diabetes (about 90%) have received a diagnosis of the condition. PRIMARY FUNDING SOURCE/BACKGROUND:National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS/RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

BACKGROUND: Ecstasy/MDMA has been one of the most prevalent party drugs for decades, and powder ecstasy recently increased in popularity. We examined trends in use to determine who to best target for prevention and harm reduction. METHODS: Secondary analysis of the 2007-2014 National Survey on Drug Use and Health, a repeated cross-sectional, nationally representative probability sample, was conducted. Linear trends in past-year ecstasy use and trends in demographic and other past-year substance use characteristics among ecstasy users were examined among participants ages 12-34 (N=332,560). RESULTS: Past-year prevalence of ecstasy use was stable across years at 2% (P=0.693). Over time, the proportion of ecstasy users with a college degree increased from 11.5% in 2007/08 to 24.5% in 2013/14 (P<0.001). The proportion of users who were age 12-17 decreased, as did proportions of users who are non-Hispanic black, and reported income <$20,000/year (Ps<0.001). Prevalence of past-year use of marijuana, LSD, ketamine, and DMT/AMT/Foxy increased among ecstasy users (Ps<0.05); DMT/AMT/Foxy use increased more than four-fold from 2.1% in 2007/08 to 8.7% in 2013/14. Perception of great risk associated with LSD use decreased among users and ease of obtaining LSD increased (Ps<0.05). Past-year use of 5 or more other substances also increased over time (P<0.05). CONCLUSIONS: Ecstasy use in the US appears to be increasing among those with college degrees and use of other substances among ecstasy users is growing-particularly use of otherwise rare substances such as tryptamines. Results inform prevention and harm reduction strategies in this increasingly shifting group of ecstasy users.

OBJECTIVE:This study evaluated the impact of an integrated behavioral health home (BHH) pilot on adults with psychotic and bipolar disorders. METHODS:Quasi-experimental methods were used to compare outcomes before (September 2014-August 2015) and after the intervention (September 2015-August 2016) among ambulatory BHH patients and a control group. Electronic health records were compared between 424 BHH patients (N=369, psychotic disorder; N=55, bipolar disorder) and 1,521 individuals from the same urban, safety-net health system who were not enrolled in the BHH. Groups were weighted by propensity score on the basis of sex, age, race-ethnicity, language, 2010 U.S. Census block group characteristics, Medicare and Medicaid enrollment, and diabetes diagnosis. RESULTS:BHH patients had fewer total psychiatric hospitalizations and fewer total emergency visits compared with the control group, a difference that was predominantly driven by patients with at least one psychiatric hospitalization or ED visit. There were no differences in medical hospitalizations. Although BHH patients were more likely to receive HbA1c screening, there were no differences between the groups in lipid monitoring. Regarding secondary outcomes, there were no significant differences in changes in metabolic monitoring parameters among patients with diabetes. CONCLUSIONS:Participation in a pilot ambulatory BHH program among patients with psychotic and bipolar disorders was associated with significant reductions in ED visits and psychiatric hospitalizations and increased HbA1c monitoring. This evaluation builds on prior research by specifying intervention details and the clinical target population, strengthening the evidence base for care integration to support further program dissemination.

BACKGROUND: Despite reductions in youth pedestrian and bicyclist deaths over the past two decades, these injuries remain a substantial cause of morbidity and mortality for children and adolescents. There is a need for additional information on non-fatal pediatric pedestrian injuries and the role of traumatic brain injury (TBI), a leading cause of acquired disability. METHODS: Using a multi-year national sample of emergency department (ED) records, we estimated annual motorized-vehicle related pediatric pedestrian and bicyclist (i.e. pedalcyclist) injury rates by age and region. We modeled in-hospital fatality risk controlling for age, gender, injury severity, TBI, and trauma center status. RESULTS: ED visits for pediatric pedestrian injuries declined 19.3% (95% CI 16.8, 21.8) from 2006 to 2012, with the largest decreases in 5-to-9 year olds and 10-to-14 year olds. Case fatality rates also declined 14.0%. There was no significant change in bicyclist injury rates. TBI was implicated in 6.7% (95% CI 6.3, 7.1) of all pedestrian and bicyclist injuries and 55.5% (95% CI 27.9, 83.1) of fatalities. Pedestrian ED visits were more likely to be fatal than bicyclist injuries (aOR = 2.4, 95% CI 2.3, 2.6), with significant additive interaction between pedestrian status and TBI. CONCLUSIONS: TBI in young pedestrian ED patients was associated with a higher risk of mortality compared to cyclists. There is a role for concurrent clinical focus on TBI recovery alongside ongoing efforts to mitigate and prevent motor vehicle crashes with pedestrians and bicyclists. Differences between youth pedestrian and cycling injury trends merit further exploration and localized analyses, with respect to behavior patterns and interventions. ED data captures a substantially larger number of pediatric pedestrian injuries compared to crash reports and can play a role in those analyses.