Faculty Bibliography

BACKGROUND:End-stage kidney disease (ESKD) is a significant public health concern disproportionately affecting African Americans (AAs). Type 2 diabetes (T2D) is the leading cause of ESKD in the USA, and efforts to uncover genetic susceptibility to diabetic kidney disease (DKD) have had limited success. A prior genome-wide association study (GWAS) in AAs with T2D-ESKD was expanded with additional AA cases and controls and genotypes imputed to the higher density 1000 Genomes reference panel. The discovery analysis included 3432 T2D-ESKD cases and 6977 non-diabetic non-nephropathy controls (N = 10,409), followed by a discrimination analysis in 2756 T2D non-nephropathy controls to exclude T2D-associated variants. RESULTS:, OR = 1.46) remained associated with all-cause ESKD in the APOL1-negative analysis. CONCLUSIONS:Findings provide further evidence for genetic factors associated with advanced kidney disease in AAs with T2D.

BACKGROUND AND OBJECTIVES:The association between plant-based diets, incident CKD, and kidney function decline has not been examined in the general population. We prospectively investigated this relationship in a population-based study, and evaluated if risk varied by different types of plant-based diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Analyses were conducted in a sample of 14,686 middle-aged adults enrolled in the Atherosclerosis Risk in Communities study. Diets were characterized using four plant-based diet indices. In the overall plant-based diet index, all plant foods were positively scored; in the healthy plant-based diet index, only healthful plant foods were positively scored; in the provegetarian diet, selected plant foods were positively scored. In the less healthy plant-based diet index, only less healthful plant foods were positively scored. All indices negatively scored animal foods. We used Cox proportional hazards models to study the association with incident CKD and linear mixed models to examine decline in eGFR, adjusting for confounders. RESULTS:for trend =0.04) was associated with an elevated risk. Higher adherence to an overall plant-based diet and a healthy plant-based diet was associated with slower eGFR decline. The proportion of CKD attributable to lower adherence to healthy plant-based diets was 4.1% (95% CI, 0.6% to 8.3%). CONCLUSIONS:Higher adherence to healthy plant-based diets and a vegetarian diet was associated with favorable kidney disease outcomes.

IMPORTANCE:Brain atrophy and vascular lesions contribute to dementia and mild cognitive impairment (MCI) in clinical referral populations. Prospective evidence in older general populations is limited. OBJECTIVE:To evaluate which magnetic resonance imaging (MRI) signs are independent risk factors for dementia and MCI. DESIGN, SETTING, AND PARTICIPANTS:This population-based cohort study included 1553 participants sampled from the Atherosclerosis Risk in Communities Study who had brain MRI scans and were dementia free during visit 5 (June 2011 to September 2013). Participants' cognitive status was evaluated through visit 6 (June 2016 to December 2017). EXPOSURES:Brain regional volumes, microhemorrhages, white matter hyperintensity (WMH) volumes, and infarcts measured on 3-T MRI. MAIN OUTCOMES AND MEASURES:Cognitive status (dementia, MCI, or nonimpaired cognition) was determined from in-person evaluations. Dementia among participants who missed visit 6 was identified via dementia surveillance and hospital discharge or death certificate codes. Cox proportional hazards models were used to evaluate the risk of dementia in 3 populations: dementia-free participants (N = 1553), participants with nonimpaired cognition (n = 1014), and participants with MCI (n = 539). Complementary log-log models were used for risk of MCI among participants with nonimpaired cognition who also attended visit 6 (n = 767). Models were adjusted for demographic variables, apolipoprotein E ε4 alleles, vascular risk factors, depressive symptoms, and heart failure. RESULTS:Overall, 212 incident dementia cases were identified among 1553 participants (mean [SD] age at visit 5, 76 [5.2] years; 946 [60.9%] women; 436 [28.1%] African American) with a median (interquartile range) follow-up period of 4.9 (4.3-5.2) years. Significant risk factors of dementia included lower volumes in the Alzheimer disease (AD) signature region, including hippocampus, entorhinal cortex, and surrounding structures (hazard ratio [HR] per 1-SD decrease, 2.40; 95% CI, 1.89-3.04), lobar microhemorrhages (HR, 1.90; 95% CI, 1.30-2.77), higher volumes of WMH (HR per 1-SD increase, 1.44; 95% CI, 1.23-1.69), and lacunar infarcts (HR, 1.66; 95% CI, 1.20-2.31). The AD signature region volume was also consistently associated with both MCI and progression from MCI to dementia, while subcortical microhemorrhages and infarcts contributed less to the progression from MCI to dementia. CONCLUSIONS AND RELEVANCE:In this study, lower AD signature region volumes, brain microhemorrhages, higher WMH volumes, and infarcts were risk factors associated with dementia in older community-based residents. Vascular changes were more important in the development of MCI than in its progression to dementia, while AD-related signs were important in both stages.

BACKGROUND:Complementary and alternative medicines (CAM) are associated with poor asthma medication adherence, a major risk factor for asthma exacerbation. However, previous studies showed inconsistent relationships between CAM use and asthma control due to small sample sizes, demographic differences across populations studied, and poor differentiation of CAM types. METHODS:We examined associations between CAM use and asthma exacerbation using a cross-sectional analysis of the 2012 National Health Interview Survey. We included adults ≥18 years with current asthma (n = 2,736) to analyze racial/ethnic differences in CAM use as well as the association between CAM use and both asthma exacerbation and emergency department (ED) visit for asthma exacerbation across racial/ethnic groups. We ran descriptive statistics and multivariable logistic regressions. RESULT/RESULTS:Blacks (OR = 0.63 [0.49-0.81]) and Hispanics (OR = 0.66 [0.48-0.92]) had decreased odds of using CAM compared to Whites. Overall, there was no association between CAM use and asthma exacerbation (OR = 0.99 [0.79-1.25]) but the subgroup of 'other complementary approaches' was associated with increased odds of asthma exacerbation among all survey respondents (1.90 [1.21-2.97]), Whites (OR = 1.90 [1.21-2.97]), and Hispanics (OR = 1.43 [0.98-2.09). CAM use was associated with decreased odds of an ED visit for asthma exacerbation (OR = 0.65 [0.45-0.93]). These associations were different among racial/ethnic groups with decreased odds of ED visit among Whites (OR = 0.50 [0.32-0.78]) but no association among Blacks and Hispanics. CONCLUSION/CONCLUSIONS:We found that both CAM use and the association between CAM use and asthma exacerbation varied by racial/ethnic group. The different relationship may arise from how CAM is used to complement or to substitute for conventional asthma management.

INTRODUCTION/BACKGROUND:The present study measures how racially-targeted food and beverage ads affect adolescents' attitudes toward ads and brands, purchase intentions for advertised products, and willingness to engage with brands on social media. METHODS:Black and White adolescents were recruited through Survey Sampling International in 2016. Participants completed an online survey in which they were randomized to view either four food and beverage ads (e.g., soda, candy commercials) featuring Black actors or four food and beverage ads featuring White actors. RESULTS:For the two components of the attitudinal outcome, Black participants were more likely to report a positive affective response toward racially-similar ads compared to Whites. However, White participants were more likely to like ads that were racially-dissimilar compared to Black participants. Data were analyzed in 2016-2017, and we used an alpha level of 0.05 to denote statistical significance. CONCLUSIONS:Both Black and White adolescents reported more positive affective responses to ads that featured Blacks compared to ads that featured Whites. Because there were no differences on two outcomes, future research should examine the influence of racially-targeted marketing in real-world contexts (e.g., social media) and longitudinal exposure to targeted advertising on dietary behavior.

Novel synthetic opioids include various analogs of fentanyl and emerging non-fentanyl compounds with different chemical structures, such as AH-7921, MT-45 and U-47700. In recent years, these drugs have rapidly emerged on the drug market, and their abuse has been increasing worldwide. The motivations for use of these new compounds include their legal status, ready availability, low cost, users' curiosity or preference for their particular pharmacological properties and the intention to avoid detection. Furthermore, more common drugs like heroin are now increasingly being replaced or cut with fentanyl or new designer opioids; thus, many drug users are unintentionally or unknowingly using synthetic fentanyl analogs. In this scenario, the detection of new psychoactive substances in hair can provide insight into their current diffusion among the population and social characteristics of these synthetic drug users. In this manuscript, we describe a simple, fast, specific and sensitive UHPLC-MS-MS method able to detect 13 synthetic opioids (including fentanyl analogs) and metabolites in hair samples. Furthermore, the method includes the detection of 4-anilino-N-phenethyl-piperidine (4-ANPP), which is considered both a precursor and a metabolite of several fentanyl analogs. The method was applied to 34 real hair samples collected in New York City from subjects who had reported past-year non-medical opioid and/or heroin use. In total, 17 samples tested positive for at least one target analyte, with oxycodone (nine samples) and tramadol (eight samples) being the most common. Among these, the method was able to quantify furanyl-fentanyl and fentanyl in the pg/mg range in two samples. Simultaneously, also 4-ANPP was detected, giving evidence for the first time that this compound can be selected as a marker of fentanyl analogs use via hair testing. In conclusion, this study confirmed the increasing diffusion of new synthetic opioids and "fentalogs" with high potency among non-medical opioid users.

BACKGROUND:Estimation of glomerular filtration rate (GFR) using estimated glomerular filtration rate creatinine (eGFRcr) is central to clinical practice but has limitations. We tested the hypothesis that serum metabolomic profiling can identify novel markers that in combination can provide more accurate GFR estimates. METHODS:We performed a cross-sectional study of 200 African American Study of Kidney Disease and Hypertension (AASK) and 265 Multi-Ethnic Study of Atherosclerosis (MESA) participants with measured GFR (mGFR). Untargeted gas chromatography/dual mass spectrometry- and liquid chromatography/dual mass spectrometry-based quantification was followed by the development of targeted assays for 15 metabolites. On the log scale, GFR was estimated from single- and multiple-metabolite panels and compared with eGFR using the Chronic Kidney Disease Epidemiology equations with creatinine and/or cystatin C using established metrics, including the proportion of errors >30% of mGFR (1-P30), before and after bias correction. RESULTS:Of untargeted metabolites in the AASK and MESA, 283 of 780 (36%) and 387 of 1447 (27%), respectively, were significantly correlated (P ≤ 0.001) with mGFR. A targeted metabolite panel eGFR developed in the AASK and validated in the MESA was more accurate (1-P30 3.7 and 1.9%, respectively) than eGFRcr [11.2 and 18.5%, respectively (P < 0.001 for both)] and estimating GFR using cystatin C (eGFRcys) [10.6% (P = 0.02) and 9.1% (P < 0.05), respectively] but was not consistently better than eGFR using both creatinine and cystatin C [3.7% (P > 0.05) and 9.1% (P < 0.05), respectively]. A panel excluding creatinine and demographics still performed well [1-P30 6.4% (P = 0.11) and 3.4% (P < 0.001) in the AASK and MESA] versus eGFRcr. CONCLUSIONS:Multimetabolite panels can enable accurate GFR estimation. Metabolomic equations, preferably excluding creatinine and demographic characteristics, should be tested for robustness and generalizability as a potential confirmatory test when eGFRcr is unreliable.

OBJECTIVE:To determine if preterm birth, defined as gestational age <37 weeks, is lower for women living in counties with higher well-being, after accounting for known individual risk factors. DESIGN:Cross-sectional study of all US births in 2011. PARTICIPANTS:We obtained birth data from the National Center for Health Statistics which included 3 938 985 individuals. MAIN OUTCOMES MEASURES:Primary outcome measure was maternal risk of preterm delivery by county; primary independent variable was county-level well-being as measured by the Gallup-Sharecare Well-Being Index (WBI). RESULTS:Women living in counties with higher population well-being had a lower rate of preterm delivery. The rate of preterm birth in counties in the lowest WBI quintile was 13.1%, while the rate of preterm birth in counties in the highest WBI quintile was 10.9%. In the model adjusted for maternal risk factors (age, race, Hispanic ethnicity, smoking status, timing of initiation of prenatal visits, multiparity, maternal insurance payer), the association was slightly attenuated with an absolute difference of 1.9% (95% CI 1.7% to 2.1%; p<0.001). CONCLUSIONS:Pregnant women who live in areas with higher population well-being have lower risk of preterm birth, even after accounting for individual risk factors.

Background: Older adults with diabetes continue to be overtreated despite current guidelines recommending less aggressive target A1c levels based on life expectancy. The suboptimal management of this vulnerable population could be due to physicians having conflicting beliefs regarding this guideline or simply lacking awareness, and changing these behaviors is challenging. Clinical decision support (CDS) within the electronic health record (EHR) has the potential to address this issue, but effectiveness is undermined by alert fatigue and poor workflow integration. Incorporating behavioral economics into CDS tools is an innovative approach to improve adherence to these guidelines while reducing physician burden, and offers the promise of improving care in this population.
Method(s): We applied a systematic, user-centered approach to incorporate behavioral economic " nudges" into a CDS module and performed user testing in six pilot primary care practices in a large academic medical center. To build the nudges, we conducted: (1) semi-structured interviews with key informants (n=8); (2) a two-hour design thinking workshop to derive and refine initial module ideas; and (3) semi-structured group interviews at each site with clinic leaders and clinicians to elicit feedback on the module components. Clinicians were observed using the module in practice; detailed field notes were collected and summarized by module idea and usability theme for rapid iteration and refinement. Frequency of firing and user action taken were assessed in the first month of implementation via EHR reporting to confirm that module components and reporting were working as expected, and to assess utilization.
Result(s): Insights from key stakeholder and clinician group interviews identified the refill protocol, inbasket lab result, and medication preference list as candidate EHR CDS targets for the module. A new EHR navigator section notification and peer comparison message, derived from the design workshop, were also prototyped and produced. User feedback from site visits confirmed compatibility with clinical workflows, and contributed to refinement of design and content. The initial prototypes were first piloted at two sites, refined, and then activated at an additional four additional sites. Preliminary Results for the six clinics indicate that over approximately 31 weeks: 1) the navigator alert fired 1047 times for 53 unique clinicians, and 2) the refill protocol alert fired 421 times for 53 unique clinicians. Reports for the other " nudges" are in development.
Conclusion(s): Integrating behavioral economic nudges into the EHR is a promising approach to enhancing guideline awareness and adherence for older adults with diabetes. This novel pilot will demonstrate the initial feasibility and preliminary efficacy of this strategy and determine if a full-scale effectiveness trial is warranted