Faculty Bibliography

BACKGROUND: Perfluoroalkyl acids are synthetic compounds widely used in industrial and commercial applications. Laboratory studies suggest that these persistent and bioaccumulative chemicals produce oxidant stress and damage glomerular endothelial cells, raising concern regarding the impact of these compounds on renal function. METHODS: We performed cross-sectional analyses of data 1960 participants aged 12-19 years of the 2003-2010 National Health and Nutrition Examination Surveys. PFAA exposure was assessed using levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid, and perfluorohexane sulfonic acid. Primary study outcomes were estimated glomerular filtration rate (eGFR) and serum uric acid. RESULTS: While adjusting for demographics, cotinine, prehypertension, insulin resistance, body mass index, and hypercholesterolemia, adolescents in the highest PFOA and PFOS quartile had a lower eGFR, 6.84 mL/min/1.73 m2 (95 % CI: 2.19 to 11.48) and 9.69 mL/min/1.73 m2 (95 % CI: -4.59 to 14.78), respectively, compared to the lowest quartile. Highest PFOA and PFOS quartiles were also associated with 0.21 mg/dL (95 % CI: 0.056 to 0.37) and 0.19 mg/dL (95 % CI: 0.032 to 0.34) increases in uric acid, respectively. CONCLUSIONS: PFAAs are associated with a reduction in kidney function and increased uric acid levels in otherwise healthy adolescents. Reverse causation and residual confounding could explain the results. Our study results confirm and amplify previous findings, though longitudinal studies examining prenatal and childhood biomarkers in relationship with robust measures of childhood renal function are needed.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines, including interleukin (IL)-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], tumor necrosis factor (TNF) receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1alpha and IL-1beta), promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1alpha, IL-1beta, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin, yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indices of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1alpha, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient as compared to wild-type mice, no genotype-related differences in the other indices existed following O3 exposure. O3 caused AHR to acetyl-beta-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were non-existent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.

BACKGROUND: Obesity is highly prevalent among Veterans. In the United States, the Veterans Health Administration (VHA) offers a comprehensive weight management program called MOVE!. Yet, fewer than 10 % of eligible patients ever attend one MOVE! visit. The VHA has a patient-centered medical home (PCMH) model of primary care (PC) called Patient-Aligned Care Teams (PACT) at all Veterans Affairs (VA) Medical Centers. PACT teamlets conduct obesity screening, weight management counseling, and refer to MOVE!. As part of a needs assessment to improve delivery of weight management services, the purpose of this study was to assess PACT teamlet and MOVE! staff: 1) current attitudes and perceptions regarding obesity care; 2) obesity-related counseling practices 3) experiences with the MOVE! program; and 4) targets for interventions to improve implementation of obesity care in the PC setting. METHODS: We recruited 25 PACT teamlet members from a single VA study site-11 PC physicians, 5 registered nurses, 5 licensed practical nurses, 1 clerical assistant, and 3 MOVE! staff (2 dietitians, 1 psychologist)-for individual interviews using a combination of convenience and snowball sampling. Audio recorded interviews were professionally transcribed and iteratively coded by two independent reviewers. The analytic process was guided by discourse analysis in order to discover how the participants perceived and provided weight management care and what specific attitudes affected their practices, all as bounded within the organization. RESULTS: Emerging themes included: 1) role perceptions, 2) anticipated outcomes of weight management counseling and programs, and 3) communication and information dissemination. Perceived role among PCPs was influenced by training, whereas personal experience with their own weight management impacted role perception among LPNs/RNs. Attitudes about whether or not they could impact patients' weight outcomes via counseling or referral to MOVE! varied. System-level communication about VHA priorities through electronic health records and time allocation influenced teams to prioritize referral to MOVE! over weight management counseling. CONCLUSION: We found a diversity of attitudes, and practices within PACT, and identified factors that can enhance the MOVE! program and inform interventions to improve weight management within primary care. Although findings are site-specific, many are supported in the literature and applicable to other VA and non-VA sites with PCMH models of care.

The United States system of immigrant detention centers has been the subject of considerable scrutiny with respect to health care of detainees. We sought to characterize the rates and types of deaths that have occurred within this system between the years 2003-2015. We analyzed a file of detainee deaths released by the U.S. Department of Homeland Security as part of a freedom of information request. Between 2003 and 2015, 150 deaths were recorded. During this time period, the annual rate of death among detainees dropped dramatically, whether measured by annual admissions or by person years of exposure. The most common causes of death were cardiovascular, cancer and suicide. More research is needed to adequately account for the contributors to these declining rates of death in immigration detention settings.

BACKGROUND:We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. METHODS AND RESULTS/RESULTS:mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run-in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone-delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician-written, theory-based algorithm using real-time activity data and 16 personal factors with a 10 000 steps/day goal. Forty-eight outpatients (46% women, 21% nonwhite) enrolled with a mean±SD age of 58±8 years, body mass index of 31±6 kg/m(2), and baseline activity of 9670±4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [CI], -580 to 2628; P=0.21). In phase II, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95% CI, 1318 to 3750; P<0.001) and over blinded controls by 3376 (95% CI, 1951 to 4801; P<0.001). CONCLUSIONS:An automated tracking-texting intervention increased physical activity with, but not without, the texting component. These results support new mHealth tracking technologies as facilitators in need of behavior change drivers. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://ClinicalTrials.gov/. Unique identifier: NCT01917812.

BACKGROUND: The Global Alliance for Chronic Diseases comprises the majority of the world's public research funding agencies. It is focussed on implementation research to tackle the burden of chronic diseases in low- and middle-income countries and amongst vulnerable populations in high-income countries. In its inaugural research call, 15 projects were funded, focussing on lowering blood pressure-related disease burden. In this study, we describe a reflexive mapping exercise to identify the behaviour change strategies undertaken in each of these projects. METHODS: Using the Behaviour Change Wheel framework, each team rated the capability, opportunity and motivation of the various actors who were integral to each project (e.g. community members, non-physician health workers and doctors in projects focussed on service delivery). Teams then mapped the interventions they were implementing and determined the principal policy categories in which those interventions were operating. Guidance was provided on the use of Behaviour Change Wheel to support consistency in responses across teams. Ratings were iteratively discussed and refined at several group meetings. RESULTS: There was marked variation in the perceived capabilities, opportunities and motivation of the various actors who were being targeted for behaviour change strategies. Despite this variation, there was a high degree of synergy in interventions functions with most teams utilising complex interventions involving education, training, enablement, environmental restructuring and persuasion oriented strategies. Similar policy categories were also targeted across teams particularly in the areas of guidelines, communication/marketing and service provision with few teams focussing on fiscal measures, regulation and legislation. CONCLUSIONS: The large variation in preparedness to change behaviour amongst the principal actors across these projects suggests that the interventions themselves will be variably taken up, despite the similarity in approaches taken. The findings highlight the importance of contextual factors in driving success and failure of research programmes. Forthcoming outcome and process evaluations from each project will build on this exploratory work and provide a greater understanding of factors that might influence scale-up of intervention strategies.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Previous studies demonstrated a higher risk of CKD in persons with a history of kidney stones, but these studies examined mostly white populations and did not evaluate important potential interactions such as race and plasma uric acid. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:In 10,678 Atherosclerosis Risk in Communities (ARIC) study participants free of CKD at baseline (ARIC visit 4 in 1996-1998), we assessed the association between a history of nephrolithiasis (a time-varying variable, defined by a combination of self-report and diagnostic codes) and incident CKD (defined by diagnostic codes from linkage to hospitalizations and US Centers for Medicare and Medicaid Services' records). RESULTS:At baseline, 856 participants had a history of nephrolithiasis; 322 developed nephrolithiasis during follow-up. Over a mean follow-up of 12 years, there were 1037 incident CKD events. Nephrolithiasis history was associated with a 29% (hazard ratio [HR], 1.29; 95% confidence interval [95% CI], 1.07 to 1.54) higher risk of CKD in demographic-adjusted analyses, but the association was no longer statistically significant after multivariable adjustment (HR, 1.09; 95% CI, 0.90 to 1.32). The multivariable-adjusted association was stronger among participants with plasma uric acid levels ≤6 mg/dl (HR, 1.34; 95% CI, 1.05 to 1.72) compared with those with levels >6 mg/dl (HR, 0.94; 95% CI, 0.70 to 1.28; P(interaction) = 0.05). There was no interaction of stone disease and race with incident CKD. CONCLUSIONS:In this community-based cohort, nephrolithiasis was not an independent risk factor for incident CKD overall. However, risk of CKD was unexpectedly elevated in participants with stone disease and lower plasma uric acid levels.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Liver fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) are urinary markers of tubular injury that may also be markers of chronic kidney damage. We evaluated the association of these markers with incident ESRD in a community-based sample from the Atherosclerosis Risk in Communities Study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:This was a matched case-control study of 135 patients with ESRD and 186 controls who were matched on sex, race, kidney function, and diabetes status at baseline (Atherosclerosis Risk in Communities Study visit 4, 1996-1998). Urinary KIM-1 indexed to creatinine (Cr), NAG/Cr, NGAL/Cr, and L-FABP/Cr were measured in stored spot urine samples from the baseline examination. Associations of KIM-1/Cr, NAG/Cr, and NGAL/Cr with patients with incident ESRD through 2008 were modeled continuously and categorically (quartiles) using conditional logistic regression. L-FABP/Cr was modeled only categorically because of a large number of measurements below the lower limit of detection for the assay (2.4 ng/ml). RESULTS:No significant associations were observed for NAG/Cr, NGAL/Cr, or L-FABP/Cr with ESRD. Those in the highest category for KIM-1/Cr had a higher risk of ESRD compared with those with undetectable biomarker levels (reference group) in unadjusted models (odds ratio, 2.24; 95% confidence interval, 1.97 to 4.69; P=0.03) or adjustment for age (odds ratio, 2.23; 95% confidence interval, 1.06 to 4.67; P=0.03). This association was attenuated with additional adjustment for baseline kidney function (odds ratio, 2.02; 95% confidence interval, 0.95 to 4.31; P=0.07 after additional adjustment for eGFR and natural log of the urinary albumin-to-creatinine ratio). No association between KIM-1/Cr and ESRD was found when KIM-1/Cr was analyzed as a continuous variable. CONCLUSIONS:Elevated urinary KIM-1/Cr may be associated with a higher risk of incident ESRD, but it does not add to risk prediction after accounting for traditional markers of kidney function in this population.

BACKGROUND:Flow-mediated dilation (FMD) is used to assess endothelial function through changes in vascular diameter after hyperemia. High-fat meal (HFM) has been shown to induce endothelial dysfunction; recent studies, however, reported conflicting results in obese African American women (AAW). Differences in the method used to analyze FMD may explain these discrepancies. METHODS AND RESULTS/RESULTS:In protocol 1, we assessed the time course of FMD and compared the repeatability of FMD using the individual maximum peak dilation (FMDpeak) and the dilation at 60 seconds (FMD60). Sixteen AAW (age, 42±10.4 years; body mass index [BMI], 39±5.8 kg/m(2)) were studied on 2 occasions, 4 weeks apart, under fasting conditions (study 1 and study 2). In protocol 2, we used the most repeatable measurement from protocol 1 to assess changes in endothelial function after an HFM in 17 AAW (agen 42±11.1 years; BMIn 38±5.6 kg/m(2)). We found that FMDpeak was the most repeatable measurement (N=16; study 1, 5.31±3.12% and study 2, 5.80±2.91%; r=0.94). After an HFM, the baseline brachial artery diameter significantly increased at 2 hours (0.10 mm; 95% confidence interval [CI], 0.01-0.18; P=0.03) and at 4 hours (0.17 mm; 95% CI, 0.09-0.25; P<0.001). At 2 hours, the FMDpeak decreased compared with pre-HFM (-1.76; 95% CI, -3.55-0.02; P≤0.05). CONCLUSIONS:The individual's maximum peak dilation after hyperemia is the most consistent measure to assess the effect of an HFM on endothelial function. Endothelial dysfunction occurred at 2 hours after an HFM in AAW. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: https://clinicaltrials.gov/ Unique identifiers: NCT01334554 and NCT02126735.