Faculty Bibliography

Molly has been the street name for powder or crystalline ecstasy (3,4-methylenedioxymethamphetamine [MDMA[) in the United States since at least 2008; however, few studies have examined Molly use or included Molly in the definition of ecstasy/MDMA. Prevalence of self-reported ecstasy use is being underreported on surveys due to the lack of inclusion of "Molly", although Molly is often so adulterated with novel psychoactive substances such as synthetic cathinones ("bath salts") that the name "Molly" may no longer adequately represent ecstasy/MDMA. The author recommends that Molly use and Molly purity be further studied to more adequately inform prevention and harm reduction.

Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.

Longitudinal studies of cognitive performance are sensitive to dropout, as participants experiencing cognitive deficits are less likely to attend study visits, which may bias estimated associations between exposures of interest and cognitive decline. Multiple imputation is a powerful tool for handling missing data, however its use for missing cognitive outcome measures in longitudinal analyses remains limited. We use multiple imputation by chained equations (MICE) to impute cognitive performance scores of participants who did not attend the 2011-2013 exam of the Atherosclerosis Risk in Communities Study. We examined the validity of imputed scores using observed and simulated data under varying assumptions. We examined differences in the estimated association between diabetes at baseline and 20-year cognitive decline with and without imputed values. Lastly, we discuss how different analytic methods (mixed models and models fit using generalized estimate equations) and choice of for whom to impute result in different estimands. Validation using observed data showed MICE produced unbiased imputations. Simulations showed a substantial reduction in the bias of the 20-year association between diabetes and cognitive decline comparing MICE (3-4 % bias) to analyses of available data only (16-23 % bias) in a construct where missingness was strongly informative but realistic. Associations between diabetes and 20-year cognitive decline were substantially stronger with MICE than in available-case analyses. Our study suggests when informative data are available for non-examined participants, MICE can be an effective tool for imputing cognitive performance and improving assessment of cognitive decline, though careful thought should be given to target imputation population and analytic model chosen, as they may yield different estimands.

Cardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3-6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 μM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.

Data from a cross-sectional study of a clinic-based sample of older people living with HIV (PLWH; n = 100) were used to examine associations between biomarkers of physical health and neurocognitive impairment (NCI). In this sample, anemia, chronic kidney disease (CKD) stages 4-5, and hypocalcemia were associated with impairment in executive functioning or processing speed. Furthermore, participants with anemia were more likely to have CD4+ T cell counts <200 cells/mm3 (chi2 [1] = 19.57, p < .001); hypocalcemia (chi2 [1] = 17.55, p < .001); and CKD 4-5 (chi2 [2] = 10.12, p = .006). Black and Hispanic participants were more likely to be anemic compared to other races and ethnicities (chi2 [3] = 12.76, p = .005). Common medical conditions (e.g., anemia, hypocalcemia, CKD) should be investigated as potential contributors to NCI in older PLWH. Additionally, laboratory testing in racial/ethnic minority PLWH may help inform NCI screening.

BACKGROUND:Impaired functional status attenuates the relationship of systolic blood pressure (SBP) with mortality in older adults but has not been studied in middle-aged populations. METHOD:Among 10,264 stroke-free Atherosclerosis Risk in Communities participants (mean age 62.8 [5.7] years; 6,349 [62%] younger [<65 years]; 5,148 [50%] men; 2,664 [26%] Black), function was defined as good function (GF) for those self-reporting no difficulty performing functional tasks and basic or instrumental tasks of daily living; all others were defined as impaired function (IF). SBP categories were normal (<120 mmHg), prehypertension (120-139 mmHg), and hypertension (≥140 mmHg). Mortality risk associated with SBP was estimated using adjusted Cox proportional hazard models with a triple interaction between age, functional status, and SBP. RESULTS:Mean follow-up was 12.9 years with 2,863 (28%) deaths. Among younger participants, 3,017 (48%) had IF; 2,279 of 3,915 (58%) older participants had IF. Prehypertension (hazard ratio [HR] = 1.48 [1.03, 2.15] p = .04) and hypertension (HR = 1.97 [1.29, 3.03] p = .002) were associated with mortality in younger GF and older (≥65 years) GF participants (prehypertension HR = 1.21 [1.06, 1.37] p = .005; hypertension HR = 1.47 [1.36, 1.59] p < .001). Among IF participants, prehypertension was not associated with mortality in younger participants (HR = 0.99 [0.85, 1.15] p = .93) and was protective in older participants (HR = 0.87 [0.85, 0.90] p < .001). Hypertension was associated with mortality in younger IF participants (HR = 1.54 [1.30, 1.82] p < .001) but not in older IF participants (HR = 0.99 [0.87, 1.14] p = .93). CONCLUSIONS:Compared with younger and well-functioning persons, the additional contribution of blood pressure to mortality is much lower with older age and impaired function, particularly if both are present. Functional status and age could potentially inform optimal blood pressure targets.

PURPOSE: The purpose of the study is to perform a meta-analysis of studies investigating the diagnostic performance of apparent diffusion coefficient (ADC) values in separating high-risk from low-risk prostate cancer (PCa). METHODS: MEDLINE and EMBASE databases were searched in December 2015 for studies reporting diagnostic performance of ADC values for discriminating high-risk from low-risk PCa and providing sufficient data to construct 2 x 2 contingency tables. Diagnostic performance was quantitatively pooled using a bivariate random-effects model including subgroup analysis and assessment of study heterogeneity and methodological quality. RESULTS: 13 studies were included, providing 1107 tumor foci in 705 patients. Heterogeneity among studies was moderate (tau2 = 0.222). Overall sensitivity was 76.9% (95% CI 68.6-83.6%); overall specificity was 77.0% (95% CI 69.9-82.8%); and summary AUC was 0.67. Inverse correlation between sensitivity and specificity (rho = -0.58) indicated interstudy heterogeneity was partly due to variation in threshold for test positivity. Primary biases were readers' knowledge of Gleason score during ADC measurement, lack of prespecified ADC thresholds, and lack of prostatectomy as reference in some studies. Higher sensitivity was seen in studies published within the past 2 years and studies not using b value of at least 2000; higher specificity was associated with involvement of one, rather than two, readers measuring ADC. Field strength, coil selection, and advanced diffusion metrics did not significantly impact diagnostic performance. CONCLUSION: ADC values show moderate accuracy in separating high-risk from low-risk PCa, although important biases may overestimate performance and unexplained sources of heterogeneity likely exist. Further studies using a standardized methodology and addressing identified weaknesses may help guide the use of ADC values for clinical decision-making.

Early stress exposure is proposed to have significant lasting effects on cognitive development. The glucocorticoid hormone cortisol, a product of the hypothalamic-pituitary-adrenal (HPA) axis, is a particular focus of research, however, the majority of past research has been based on studies of older children and adults. Evidence linking cortisol levels in infancy with cognitive development is lacking. In a large cohort sample of infants (N = 1,091) oversampled for psychosocial risk, we tested whether basal cortisol levels and cortisol reactivity to emotional stressors administered at 7 and 15 months of age were associated with cognitive development measured at 15 months. Cognitive development was measured using the Mental Development Index of the Bayley Scales of Infant Development. Multiple regression analyses indicated that basal cortisol levels at 15 months, and to a lesser extent at 7 months, were inversely associated with infant cognitive development after adjusting for psychosocial and obstetric risk. The findings provide some of the first evidence that HPA axis activity in infancy is associated with early cognitive development.

PURPOSE: To examine if there was spatial misclassification in exposure to neighborhood noise complaints among a sample of low-income housing residents in New York City, comparing home-based spatial buffers and Global Positioning System (GPS) daily path buffers. METHODS: Data came from the community-based NYC Low-Income Housing, Neighborhoods and Health Study, where GPS tracking of the sample was conducted for a week (analytic n = 102). We created a GPS daily path buffer (a buffering zone drawn around GPS tracks) of 200 m and 400 m. We also used home-based buffers of 200 m and 400 m. Using these "neighborhoods" (or exposure areas), we calculated neighborhood exposure to noisy events from 311 complaints data (analytic n = 143,967). Friedman tests (to compare overall differences in neighborhood definitions) were applied. RESULTS: There were differences in neighborhood noise complaints according to the selected neighborhood definitions (P < .05). For example, the mean neighborhood noise complaint count was 1196 per square kilometer for the 400-m home-based and 812 per square kilometer for the 400-m activity space buffer, illustrating how neighborhood definition influences the estimates of exposure to neighborhood noise complaints. CONCLUSIONS: These analyses suggest that, whenever appropriate, GPS neighborhood definitions can be used in spatial epidemiology research in spatially mobile populations to understand people's lived experience.

BACKGROUND: While primary care work conditions are associated with adverse clinician outcomes, little is known about the effect of work condition interventions on quality or safety. DESIGN: A cluster randomized controlled trial of 34 clinics in the upper Midwest and New York City. PARTICIPANTS: Primary care clinicians and their diabetic and hypertensive patients. INTERVENTIONS: Quality improvement projects to improve communication between providers, workflow design, and chronic disease management. Intervention clinics received brief summaries of their clinician and patient outcome data at baseline. MAIN MEASURES: We measured work conditions and clinician and patient outcomes both at baseline and 6-12 months post-intervention. Multilevel regression analyses assessed the impact of work condition changes on outcomes. Subgroup analyses assessed impact by intervention category. KEY RESULTS: There were no significant differences in error reduction (19 % vs. 11 %, OR of improvement 1.84, 95 % CI 0.70, 4.82, p = 0.21) or quality of care improvement (19 % improved vs. 44 %, OR 0.62, 95 % CI 0.58, 1.21, p = 0.42) between intervention and control clinics. The conceptual model linking work conditions, provider outcomes, and error reduction showed significant relationships between work conditions and provider outcomes (p