Faculty Bibliography

BACKGROUND: There are limited data about the extent of DSM-5 substance use disorders (SUDs) among primary care patients. METHODS: This study analyzed data from a multisite validation study of a substance use screening instrument conducted in a diverse sample of 2000 adults aged >/=18 years recruited from five primary care practices in four states. Prevalence and correlates of 12-month DSM-5 SUDs were examined. RESULTS: Overall, 75.5% of the sample used any substance, including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids 4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0% (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%, moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12-month users, a high proportion of tobacco or drug users met criteria for a disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3% moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria for a moderate/severe disorder. Younger ages, male sex, and low education were associated with increased odds of having SUD. CONCLUSION: These findings reveal the high prevalence of SUDs in primary care and underscore the need to identify and address them.

IMPORTANCE:Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. OBJECTIVES:To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. DESIGN, SETTING, AND PARTICIPANTS:This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline. MAIN OUTCOMES AND MEASURES:Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia. RESULTS:In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean [SD] age at visit 1 of 57.4 [5.2] years) were identified among 15 744 participants. Black race (hazard ratio [HR], 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype. CONCLUSIONS AND RELEVANCE:Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

Concerns persist that individuals with substance use disorders who are under community criminal justice supervision experience circumstances that might compromise their provision of valid, informed consent for research participation. These concerns include the possibilities that desire to obtain access to treatment might lead individuals to ignore important information about research participation, including information about risks, or that cognitive impairment associated with substance use might interfere with attending to important information. We report results from a consent quiz (CQ) administered in a multisite randomized clinical trial of long-acting naltrexone to prevent relapse to opioid use disorder among adults under community criminal justice supervision-a treatment option difficult to access by this population of individuals. Participants were required to answer all 11 items correctly before randomization. On average, participants answered 9.8 items correctly (89%) at baseline first attempt (n=306). At week 21 (n=212), participants scored 87% (9.5 items correct) without review. Performance was equivalent to, or better than, published results from other populations on a basic consent quiz instrument across multiple content domains. The consent quiz is an efficient method to screen for adequate knowledge of consent information as part of the informed consent process. Clinical researchers who are concerned about these issues should consider using a consent quiz with corrected feedback to enhance the informed consent process. Overall, while primarily useful as an educational tool, employing a CQ as part of the gateway to participation in research may be particularly important as the field continues to advance and tests novel experimental treatments with significant risks and uncertain potential for benefit.

Hydroxy-4-methoxybenzophenone, also known as benzophenone-3 (BP-3), is a commonly used ultraviolet filter in skincare and as a food additive. Large concentrations of similar phenolic compounds have been detected in urine, amniotic fluid, and placental tissue, thereby raising questions about its impact on reproduction. The objective of this paper was to investigate the reproductive toxicity of BP-3 in humans and animals. In humans, studies showed that high levels of BP-3 exposure could be linked to an increase in male birth weight but a decline in female birth weight and male gestational age. In fish, BP-3 exposure resulted in a decline in egg production, hatching, and testosterone, along with a down-regulation of steroidogenic genes. In rats, a decrease in epididymal sperm density and a prolonged estrous cycle for females was observed. These positive associations may be attributed to an altered estrogen and testosterone balance as a result of endocrine disrupting effects of BP-3. However, the current body of literature is limited by non-uniform exposure and outcome measurements in studies both across and within species and future studies will need to be conducted in a standardized fashion to allow for a more significant contribution to the literature that allows for better comparison across studies.

Research Findings: Recent research has explored relations between classroom quality and child executive function (EF), but little is known about how teachers' well-being, including stress, relates to child EF-a crucial component of self-regulation. We hypothesized that teacher stress is negatively or curvilinearly related to child EF and classroom quality may be one mechanism explaining this relation. Furthermore, as working with young, low-income children may be particularly stressful, we tested the extent to which the relation between teacher stress and child EF varies by school-level poverty. Two-level hierarchical linear models using a sample of 171 kindergarten children and 33 teachers revealed a marginally significant linear relation between teacher stress and child EF (spring) controlling for baseline child EF (fall); there was no evidence for mediation by classroom quality. School-level poverty moderated the relation between teacher stress and child EF: Children attending low-poverty schools demonstrated smaller gains in EF when their teachers reported higher stress levels. However, in high-poverty schools high levels of teacher stress were not a risk factor for child EF. Practice or Policy: These novel findings are a first step to understanding how teachers' well-being relates to child EF across schools and have implications for supporting teachers.

Background: The United Arab Emirates (UAE) is experiencing increasing rates of obesity, type 2 diabetes (T2D) and its complications. We tested if soluble levels of cell surface-cleaved RAGE (sRAGE) or endogenous secretory RAGE (esRAGE), the product of alternative mRNA splicing of AGER, are associated with T2D and obesity in the UAE.
Method(s): A case-control study was performed in the Diabetes, Endocrinology and General Medical Clinics of the Sheikh Khalifa Medical City in Abu Dhabi. 216 T2D subjects and 215 controls (mean age 57.4+/-12.1 vs. 50.7+/-15.4 years, respectively) were enrolled. Plasma sRAGE and esRAGE levels, anthropomorphic characteristics and routine chemistries were measured. The relationship between sRAGE and esRAGE with obesity and T2D status was tested using a linear regression model.
Result(s): Univariate analyses comparing T2D case and control subjects revealed differences in sRAGE (1,033+/-545.3 vs. 1,169+/-664.1 pg/ml, respectively; p=0.02) but not esRAGE. Covariate adjustment revealed that differences in sRAGE were significant after correction for age and sex and additionally for waist-hip ratio (WHR); total cholesterol (TC), HDL; hsCRP; Vit D; or triglyceride (TG) levels separately. In cases or controls, we tested associations of body mass index (BMI) or WHR with sRAGE and esRAGE. In controls but not T2D cases, sRAGE and esRAGE were significantly associated with BMI, after correction for age and sex and additionally for eGFR; blood pressure; TC, HDL; hsCRP; Vit D; creatinine; TG and HbA1c in a combined model. In the case of WHR, in controls and T2D cases, there were no associations with sRAGE, but only in T2D cases, WHR was associated with esRAGE after correction for age and sex and blood pressure; TC, HDL; hsCRP, HbA1c, creatinine; TG, eGFR, Vit D and TG in a combined model.
Conclusion(s): Levels of sRAGE but not esRAGE distinguish T2D case vs. controls in the UAE population. Genetic and unique obesity-dependent factors may underlie lack of association between esRAGE in cases vs. controls, which may affect vulnerability to T2D and its complications in the UAE

Living in communities with persistent gun violence is associated with negative social, behavioral, and health outcomes, analogous to those of a natural disaster. Taking a disaster-preparedness approach may identify targets for community-based action to respond to on-going gun violence. We assessed the relevance of adapting a disaster-preparedness approach to gun violence and, specifically, the relationship between perceived collective efficacy, its subscales of social cohesion and informal social control, and exposure to gun violence. In 2014, we conducted a cross-sectional study using a community-based participatory research approach in two neighborhoods in New Haven, CT, with high violent crime rates. Participants were ≥18 years of age and English speaking. We measured exposure to gun violence by adapting the Project on Human Development in Chicago Neighborhoods Exposure to Violence Scale. We examined the association between perceived collective efficacy, measured by the Sampson Collective Efficacy Scale, and exposure to gun violence using multivariate modeling. We obtained 153 surveys (51% response rate, 14% refusal rate, and 35% non-response rate). Ninety-five percent reported hearing gunfire, 58% had friend or family member killed by gun violence, and 33% were physically present during a shooting. In the fully adjusted model, one standard deviation higher perceived collective efficacy was associated with lower reported exposure to gun violence (β = -0.91, p < 0.001). We demonstrated that it is possible to activate community members and local officials to engage in gun violence research. A novel, community-based approach adapted from disaster-preparedness literature may be an effective framework for mitigating exposure to gun violence in communities with persistent gun violence.

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, with neurodegeneration in multiple sclerosis (MS) is well established. The potential relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: To investigate the longitudinal relationship of INL volume changes with inflammatory disease activity. Methods: In this longitudinal multi-center study, spectral-domain optical coherence tomography (OCT) and clinical data were collected in 821 patients with MS, from eleven MS centres between 2010 and 2017. All patients had at least two visits (minimum follow- up of 6 months). Clinical data included EDSS score, occurring of relapses, including MS-associated optic neuritis (MSON). At each centre, automated segmentation of OCT scans was performed to obtain data on the pRNFL, GCIPL and INL. Annualized changes were calculated and generalized estimation equations were used to analyze longitudinal changes and associations with clinical measures. Results: In total, 1596 eyes from 798 patients (68.2% female), with a disease duration of 9.4 (+/-8.9) years, were included. Mean follow up duration was 2.3 years (range 0.5 to 5.2 years). Microcystic macular oedema (MMO) was present in 1.3% of eyes (20/1299 eyes). Clinical relapses other than MSON were present in 24.9% of patients, and disease progression was observed in 30.1%. In eyes with an episode of MSON during follow-up (N=61/1584), INL volume showed a significant increase over time (DELTAINL=0.01 mm3, p< 0.001), whereas in eyes without MSON during followup, no significant change in INL was observed (DELTAINL=0.00, p=0.308). Increase in INL volume in MSON eyes was related to a decrease in GCIPL volume (beta=-2.6, p=0.006). In eyes with MMO, the INL volume at the last visit was 0.06 mm3 higher compared to eyes without (p=0.003). There was no significant association between clinical relapses other than MSON, and INL volume changes (DELTAINL=0.00 mm3, p=0.773). Likewise, an in-or decrease in INL volume was independent of change of the EDSS score (OR=1.16, p=0.293, 95% CI 0.88-1.52). Conclusion: Our data demonstrate that an increase of the INL volume is associated with adjacent inflammation of the optic nerve and retina, but not with global physical disability. Therefore INL volume changes may be considered as a secondary outcome measure for anti-inflammatory treatment in MSON trials

Comprehensive and innovative strategies are needed to address and manage chronic diseases and conditions and to reduce health disparities. EmblemHealth Neighborhood Care (EHNC) sites provide community-based linkages across payers, health providers, and delivery systems and underserved communities using culturally sensitive methods tailored to meet the needs of the community. This article describes this novel initiative and early indicators of its feasibility. Three EHNC sites were established in New York City: Harlem, Cambria Heights, and Chinatown. Each site provides core health and customer services to members and the community. In addition, sites provide tailored services to meet the unique needs of each community. Preliminary data suggest that program and community members are utilizing the sites and returning for follow-up visits. Sites also demonstrate success in cross referral between EHNC teams. The EHNC program is both feasible from the payer's perspective and acceptable to diverse patient populations and settings.