Faculty Bibliography

BACKGROUND AND OBJECTIVE: Few studies have examined the possible cardiometabolic consequences of World Trade Center-related exposures on children who lived and/or attended school near the disaster site. Our objective was to compare cardiometabolic profiles of participants in the World Trade Center Health Registry (WTCHR) with a matched comparison group. METHODS: We evaluated WTCHR enrollees who resided in New York City and were born between September 11, 1993 and September 10, 2001, and a matched comparison group. We assessed exposure to dust cloud, home dust, as well as traumatic exposure, and associations with blood pressure, arterial wall stiffness, body mass index (BMI), total cholesterol, triglycerides, HDL, and LDL. RESULTS: A total of 402 participants completed the study, 222 in the comparison group and 180 in the WTCHR group. In multivariable regression analysis, after adjusting for relevant confounders we detected a weak association between participation in the WTCHR group and lower BMI (-1.12kg/m2, 95% CI -2.11, -0.12; p = 0.03), which became non-significant after adjusting for multiple comparisons. With respect to traumatic and psychosocial exposures, the only association that persisted in our multivariable model, below our predefined level of significance, was between post-traumatic stress disorder and higher BMI (2.06kg/m2, 95% CI 0.37, 3.74; p = 0.02). CONCLUSIONS: Our findings do not support an association between self-reported exposures to the WTC disaster and adverse cardiometabolic profile. However, further longitudinal studies may better inform the full extent of WTC-related conditions associated with exposure to the disaster.

Ecstasy (MDMA) has regained popularity in powder and crystalline form, known as Molly. However, it is unknown whether all Molly users are aware that Molly is ecstasy. A total of 1045 nightclub/festival-attending adults in New York City were surveyed about ecstasy/MDMA/Molly use in 2016. Users were asked if they agreed that "Molly is (or is supposed to be) ecstasy/MDMA." Of the 43.5% reporting lifetime use, 84.6% agreed that Molly is ecstasy, 9.5% disagreed, and 5.9% reported not knowing that Molly is ecstasy. Prevalence of use of other drugs (e.g., ketamine, opioids, methamphetamine, NBOMe, 2C series) was lowest among those not knowing that Molly is ecstasy, and highest among those not agreeing that Molly is ecstasy. Those not knowing that Molly is ecstasy were less likely to have used powder or crystal MDMA and less likely to have used in the past 12 months or to report intention to use again. Those disagreeing or not knowing that Molly is ecstasy were at over six times the odds of obtaining ecstasy from an unknown dealer, and those disagreeing were at four times higher odds of having suspected or found out that their ecstasy was adulterated. Results suggest that knowing or agreeing that Molly is ecstasy/MDMA can help indicate ecstasy-related risk.

The recent Kidney Disease Improving Global Outcomes 2012 CKD guidelines recommend estimating GFR from serum creatinine (eGFR_cr) as a first-line test to assess kidney function and using cystatin C or measured glomerular filtration rate (GFR) as confirmatory tests. eGFR_cr may be inaccurate in people with variation in muscle mass or diet, and eGFR_cys is not more accurate than eGFR_cr. eGFR_crcys is more accurate than either, but it is not independent of eGFR_cr. Measured GFR is not practical and is susceptible to error due to variation in clearance methods and in the behavior of exogenous filtration markers. Over the past few years, we have hypothesized, and begun to test the hypothesis, that a panel of filtration markers (panel eGFR) from a single blood draw would require fewer demographic or clinical variables and could estimate GFR as accurately as measured GFR. In this article, we describe the conceptual background and rationale for this hypothesis and summarize our work thus far including evaluation of novel low-molecular-weight proteins and metabolites and then outline how we envision that such a panel could be used in clinical practice, research, and public health.

OBJECTIVE:There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality. RESEARCH DESIGN AND METHODS:We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996-1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure. RESULTS:There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27-3.20), all-cause mortality (HR 1.73, 95% CI 1.38-2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34), and cancer mortality (HR 2.49, 95% CI 1.46-4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk. CONCLUSIONS:Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.

OBJECTIVE:Sexual minority men (SMM) in the United States continue to experience adverse health problems and psychosocial burdens. However, there is limited psychometric research seeking to quantify the life worries of this population. Informed by syndemic theory, the Life Worries Scale (LWS) was developed to measure the concerns of young SMM. METHOD/METHODS:Analyses of the scale were undertaken using baseline data (n = 665) from an ongoing cohort study of emerging adult, SMM. RESULTS:Exploratory factor analyses (EFA) of an initial set of 24 Likert-type items, followed by confirmatory factor analysis (CFA) and an exploratory structural equation model (ESEM), indicated a structure consisting of 6 domains of worries: financial stability, social stability, self esteem, loneliness, physical appearance, and physical health. These 6 subscales were highly correlated and also demonstrated high levels of internal consistency. Differences in life worries were noted across demographic states, specifically HIV serostatus, sexual attraction, housing status, and self-rated health. High levels of association were also detected between all 6 subscales with both depression and PTSD, while significant correlations were detected between suicidality and both self esteem and loneliness related worries. CONCLUSIONS:The results of our analyses provide evidence for the strong psychometric characteristics of the LWS. This newly developed instrument should be utilized in research to examine the extent to which life worries explain health outcomes and risk behaviors in sexual minority males, and may be potentially extended for use in other populations. (PsycINFO Database Record

Background: Approximately 40% of metastatic cutaneous melanoma (CM) patients do not respond to the current immunotherapy (IT) regimens, pointing to other, yet unknown factors conferring IT resistance. In addition, > 60% of patients from single-line or combined treatment (COMBO) regimens present severe immune related adverse events (irAEs). In this study we have developed a novel genomic approach interrogating expression quantitative trait loci (eQTLs) to explore weather germline genetic variation can serve as novel personalized determinant of immunotherapy response and toxicity.
Method(s): By interrogating the genome wide expression data and SNP array datasets of healthy twin cohort (MuTHER), we have identified 85 eQTLs most significantly associated with the expression of 265 immune genes. Using the MassARRAY system, the 85 SNPs were genotyped in 138 anti-CTLA-4 treated patients, 87 PD-1 treated patients, and 69 patients from combined (COMBO) treatments, collected from multi-institutional collaborations. To test the association of SNPs with IT response and irAEs, logistic regression analyses were performed for each treatment group adjusting by demographic and clinical covariates.
Result(s): We found significant associations with COMBO IT resistance for and eQTL in IL10/IL19 (OR = 4.249, p = 0.0167), which we have recently identified for association with melanoma survival and which, interestingly, is an established locus associated with the risk of several autoimmune diseases. Additionally, we also identified eQTLs that are associated with IT sensitivity; IL1-beta with resistance to anti-CTLA-4 and SPI1 with resistance to anti-PD-1. Interestingly, genomic scan of 85 eQTLs has identified novel loci predictive of severe autoimmunity and site specific irAEs in patients treated with COMBO or single-line anti- CTLA4 IT.
Conclusion(s): In this study, we report that eQTLs from IL19/IL10 locus, previously shown to predict autoimmunity risk and CM survival, is also a surrogate marker of response to COMBO IT, indicating a strong relationship between interleukin pathways and tumor immunogenicity. Novel loci have been found as predictive markers for autoimmune toxicity, in patients treated with COMBO and anti-CTLA4 IT. This is a first evidence that immunomodulatory pathways modulated by germline genetic variation can impact susceptibility to irAEs as well as IT efficacy. Currently, a large scan is underway using genome-wide genetic screens to further test the functional validity of these findings in a large collaborative setting

OBJECTIVE:Cardiovascular and renal complications contribute to higher mortality in patients with diabetes. We assessed novel and conventional predictors of mortality in African American-Diabetes Heart Study (AA-DHS) participants. RESEARCH DESIGN AND METHODS:) were assessed in 513 African Americans with type 2 diabetes; analyses were performed using Cox proportional hazards models. RESULTS:renal-risk genotypes (HR 0.07 [95% CI 0.01-0.69]) as the strongest predictors of mortality. CONCLUSIONS:non-renal-risk genotypes associated with higher mortality in African Americans with diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined.

AIM: The goal of the present longitudinal cohort study was to examine patterns of periodontal disease progression at progressing sites and subjects defined based on linear mixed models (LMM) of clinical attachment loss (CAL) METHODS: 113 periodontally healthy and 302 periodontitis subjects had their CAL calculated bi-monthly for 12 months. LMMs were fitted for each site and the predicted CAL levels used to categorize their progression state. Participants were grouped based on the number of progressing sites into unchanged, transitional and active subjects. Patterns of periodontal disease progression were explored using descriptive statistics RESULTS: Progression occurred primarily at molars (50% of progressing sites) and interproximal sites (72%), affected a higher proportion of deep than shallow sites (2.7% vs. 0.7%), and pocketing was the main mode of progression (49%). We found a low level of agreement (47%) between the LMM and traditional approaches to determine progression such as change in CAL >/=3 mm. Fourteen percent of subjects were classified as active and among those 93% had periodontitis. The annual mean rate of progression for the progressing subjects was 0.35 mm/year CONCLUSION: Progressing sites and subjects defined based on LMMs presented patterns of disease progression similar to those previously reported in the literature.

The primary objective of this study was to investigate the relationship between neighborhood stigma and sleep in a sample of low-income housing residents in New York City. Data were derived from the NYC Low-Income Housing, Neighborhoods, and Health Study (N = 120). Adults living in low-income housing completed a survey consisting of measures of neighborhood stigma, sleep quality, and sleep duration. Neighborhood stigma and sleep were self-reported. Associations between neighborhood stigma and sleep health were analyzed using generalized linear models with cluster variance estimation. Multivariable models adjusted for age, gender, race/ethnicity, income, education, employment status, obesity, the census block percentage of non-Hispanic black residents, and the census block percentage median household income. Results indicate that a reported negative media perception of the neighborhood was negatively associated with sleep quality and duration (p < 0.01). However, additional research is needed to explore neighborhood stigma as it relates to sleep.

CONTEXT:Mindfulness practices in the workplace have experienced rapid growth, with initial evidence suggesting positive outcomes. Even so, little is known about implementing mindfulness-based interventions (MBI), especially internally driven programs led by volunteers rather than experts. OBJECTIVE:This study qualitatively explores volunteer facilitators' perceptions of a short-dose MBI (the mindfulness moment initiative) before and 6 weeks after implementation. METHODS:Mindfulness moments were 1-3-minute-guided periods of mindfulness led at the beginning of various staff meetings at an inner-city community medical center. Facilitators' perceptions were collected through thirty-one 30-minute semi-structured interviews before and after the MMI's first 6 weeks. Categorizing and connecting strategies were employed to explore the emergence of themes and patterns across responses. RESULTS:Mindfulness moment facilitators interviewed before the intervention expected their groups to experience several intra- and interpersonal benefits. After implementation, they perceived all of these benefits to have occurred, but some benefits were mentioned more frequently before than after implementation and vice versa. Five of six expected obstacles were reported after implementation, with timing issues emerging as the most frequently mentioned theme. Facilitators believed that benefits outweighed obstacles. Our data also suggested that mindfulness moments may provide managers with an additional way to address moments of tension occurring between co-workers. Most facilitators intended to continue leading mindfulness moments and wished to expand the practice to new departments. CONCLUSION:The mindfulness moment intervention may provide a way to bring mindfulness into organizations that is not dependent on formal training programs, a large time commitment, or a commitment to extended training. Prior knowledge of the obstacles and benefits found here may result in a more successful intervention.