Faculty Bibliography

BACKGROUND AND AIMS:Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort. METHODS:8127 participants from the ARIC study (4th visit, 1996-1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein-associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis. RESULTS:While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis. CONCLUSIONS:These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD.

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.

BACKGROUND: Pediatric obesity prevalence remains at historically high levels. The objective of this study was to examine secular trends in the proportions of children with overweight/obesity who received notification from a health care professional (HCP) about their unhealthy weight. METHOD: We analyzed data of 25 570 (including 8 639 overweight/obese) children aged 2-18 years collected from seven cross-sectional biennial surveys (National Health and Nutrition Examination Survey, 1999-2014), in which adolescents (16y and older) and caregivers, mostly biological mothers, of children (2-15y) were asked 'Has a doctor or other health professional ever told you that you (or your child) were overweight?' RESULTS: Approximately 90% of overweight/obese children visited HCPs at least once in the past 12 months, but only 22.12% (s.e.=1.92) in 1999 to 34.43% (2.35) in 2014 of the overweight/obese children were notified by HCPs about unhealthy weight. The biennial increase in odds of receipt of notification of unhealthy weight was 1.08 [95%CI=(1.04-1.12)]. Greater likelihood for receipt of notification was associated with being obese [OR=5.03 (4.29-5.89) vs overweight]; black [1.24 (1.06-1.46)] or Hispanic race/ethnicity [1.72 (1.45-2.04) vs white]; female sex [1.22 (1.07-1.11) vs boys]; and child's insurance status [1.31 (1.08-1.59) vs uninsured]. There was an increasing odds of being notified with increasing age: 1.00 (reference), 2.24 (2.06-2.62), 3.22 (2.50-4.13) and 4.87 (3.76-6.32) for children 2-5, 6-11, 12-16 and 16+ year old respectively. The frequency of medical contact was linearly associated with an increased likelihood of being notified. CONCLUSIONS: Notification of child's unhealthy weight by HCPs increased significantly between 1999 and 2014, but the opportunity of clinical intervention remained substantially under-utilized.International Journal of Obesity accepted article preview online, 04 May 2016. doi:10.1038/ijo.2016.85.

BACKGROUND: Childhood obesity prevalence remains high and racial/ethnic disparities may be widening. Studies have examined the role of health behavioral differences. Less is known regarding neighborhood and built environment mediators of disparities. The objective of this study is to examine the extent to which racial/ethnic disparities in elevated child body mass index (BMI) are explained by neighborhood socioeconomic status (SES) and built environment. METHODS: We collected and analyzed race/ethnicity, BMI, and geocoded address from electronic health records of 44,810 children 4 to 18years-old seen at 14 Massachusetts pediatric practices in 2011-2012. Main outcomes were BMI z-score and BMI z-score change over time. We used multivariable linear regression to examine associations between race/ethnicity and BMI z-score outcomes, sequentially adjusting for neighborhood SES and the food and physical activity environment. RESULTS: Among 44,810 children, 13.3% were black, 5.7% Hispanic, and 65.2% white. Compared to white children, BMI z-scores were higher among black (0.43units [95% CI: 0.40-0.45]) and Hispanic (0.38 [0.34-0.42]) children; black (0.06 [0.04-0.08]), but not Hispanic, children also had greater increases in BMI z-score over time. Adjusting for neighborhood SES substantially attenuated BMI z-score differences among black (0.30 [0.27-0.34]) and Hispanic children (0.28 [0.23-0.32]), while adjustment for food and physical activity environments attenuated the differences but to a lesser extent than neighborhood SES. CONCLUSIONS: Neighborhood SES and the built environment may be important drivers of childhood obesity disparities. To accelerate progress in reducing obesity disparities, interventions must be tailored to the neighborhood contexts in which families live.

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed international members of the society to assess perceptions, clinical experiences, and preferred policy responses related to global climate change. A recruitment email was sent by the ATS President in October 2015 to 5,013 international members. Subsequently, four reminder emails were sent to nonrespondents. Responses were received from 489 members in 68 countries; the response rate was 9.8%. Half of respondents reported working in countries in Asia (25%) or Europe (25%), with the remainder in South America (18%), North America (Canada and Mexico) (18%), Australia or New Zealand (9%), and Africa (6%). Survey estimate confidence intervals were +/- 5% or smaller. A high percentage of international ATS survey respondents judged that climate change is happening (96%), that it is driven by human activity (70%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (80%). A majority of respondents also indicated they are already observing health impacts of climate change among their patients; most commonly as increases in chronic disease severity from air pollution (88%), allergic symptoms from exposure to plants or mold (72%), and severe weather injuries (69%). An even larger majority anticipated seeing these climate-related health impacts in the next two decades. Respondents further indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. International ATS respondents, like their counterparts in the U.S., observed that human health is already adversely affected by climate change, and support responses to address this situation.

INTRODUCTION: Hospitalization is a unique opportunity for smoking cessation, but prior interventions have measured efficacy with narrowly defined populations. The objective of this study was to enroll smokers admitted to two "safety net" hospitals and compare the effectiveness of two post-discharge cessation interventions. DESIGN: A randomized comparative effectiveness trial was conducted. SETTING/PARTICIPANTS: At two New York City public hospitals, every hospitalized patient identified as a smoker (based on admission records) was approached. Inclusion criteria were: smoked cigarettes in the past 30 days; spoke English, Spanish, or Mandarin; had a U.S. phone number; not discharged to an institution where follow-up or smoking was limited; and not pregnant/breastfeeding. Of 18,797 patients identified as current smokers between July 2011 and April 2014, a total of 3,047 (16%) were discharged before being approached, 3,273 (17%) were not current smokers, 4,026 (21%) had no U.S. phone number, 2,831 (15%) were ineligible for other reasons, and 3,983 (21%) refused participation. In total, 1,618 (9%) participants enrolled in the study. During follow-up, 69% of participants were reached at 2 months and 68% at 6 months. INTERVENTION: At discharge, participants were randomized to multisession telephone counseling from study staff (n=804) or referral to the state quitline for proactive outreach and counseling (n=814). MAIN OUTCOME MEASURES: Self-reported abstinence at 6 months was measured. Analyses were conducted in late 2015. RESULTS: One quarter of participants were homeless or in unstable housing, 60% had a history of substance abuse, 43% reported current hazardous drinking, and half had a psychiatric diagnosis other than substance abuse. At follow-up, the rate of abstinence (30-day point prevalence) was higher in the intensive counseling arm than the quitline arm at 2 months (29.0% vs 20.7%; relative risk=1.40; 95% CI=1.13, 1.73) and 6 months (37.4% vs 31.5%; relative risk=1.19; 95% CI=1.01, 1.40). CONCLUSIONS: Intensive counseling was more effective than referral to the state quitline. Long-term abstinence was excellent in both groups. Many patients were not eligible for enrollment despite minimal exclusion criteria. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01363245.

Worldwide increases in diabetes prevalence in the face of limited medical resources have prompted international interest in innovative healthcare delivery models. Project ECHO (Extension for Community Healthcare Outcomes) is a "telementoring" program which has been shown to increase capacity for complex disease management in medically underserved regions. In contrast to a traditional telemedicine model which might connect a specialist with one patient, the ECHO model allows for multiple patients to benefit simultaneously by building new expertise. We recently applied the ECHO model to improve health outcomes of patients with complex diabetes (Endo ECHO) living in rural New Mexico. We describe the design of the Endo ECHO intervention and a 4-year, prospective program evaluation assessing health outcomes, utilization patterns, and cost-effectiveness. The Endo ECHO evaluation will demonstrate whether and to what extent this intervention improves outcomes for patients with complex diabetes living in rural New Mexico, and will serve as proof-of-concept for academic medical centers wishing to replicate the model in underserved regions around the world.

PURPOSE: Young sexual minority men smoke at higher rates relative to heterosexual peers. The purpose of this study was to examine correlates of smoking in a sample of young gay, bisexual, and other men who have sex with men (MSM) who might differ from more general and age-diverse samples of sexual minority individuals and, thus, inform tailored approaches to addressing tobacco use within this population. METHODS: Data on smoking status were examined in relation to demographics, mental health, substance use behavior, and psychosocial factors. Using multinomial logistic regression, factors were identified that differentiate current and former smokers from never smokers. RESULTS: In bivariate analysis, smoking status was related to demographic, mental health, substance use, and psychosocial factors. Most significantly, smoking status was associated with school enrollment status, current alcohol and marijuana use, and symptoms of depression. Multivariate modeling revealed that, compared to being a never smoker, the odds of current or former smoking were highest among those currently using either alcohol or marijuana. The odds of both current and former smoking were also higher among those reporting greater levels of gay community affinity. Finally, the odds of being a former smoker were higher for those reporting internalized antihomosexual prejudice. CONCLUSION: This study identifies several factors related to smoking status in a diverse sample of young sexual minority males. These findings should encourage investigations of smoking disparities among younger MSM to look beyond common smoking risk factors in an attempt to understand etiologies that may be unique to this group. Such findings may indicate multiple points of potential intervention aimed at decreasing cigarette smoking within this vulnerable population.

We administered a battery of neurocognitive tests to 100 HIV-positive men and women ages 50 to 70 seeking care at a large Northeastern urban HIV care clinic. Performance on neurocognitive assessments varied by demographic states. Across all assessments, approximately 28% of participants reached the threshold for borderline performance while 13% reached the threshold for impairment. When tests were grouped by domain of neurocognitive functioning, 12% of the sample met the threshold for impairment on executive functioning and 19% for processing speed. The findings demonstrate that neurocognitive declines may vary by domains of functioning, that disparities may exist across subpopulations of the seropositive aging population, and that these challenges may exist even in those actively engaged in HIV care.