Faculty Bibliography

BACKGROUND:The aim of this study is to determine the clinical characteristics and predictors of survival for patients with multiple metachronous esophageal tumors (MMET) and to compare the survival with patients that have single esophageal tumor (SET). METHOD:We identified all cases of primary esophageal cancer from the Surveillance, Epidemiology and End Results program database from 2000 to 2013. The primary outcome was the development of a second esophageal cancer six months after the diagnosis of the first tumor. A secondary outcome was disease-specific death from esophageal cancer. Chi-square test was used to compare the tumor and demographic characteristics of patients with SET versus the first and second tumor characteristics of patients with MMET. Logistic regression was used to obtain the odds ratios between patients with secondary tumors and those with primary tumors. Accelerated life model was performed for patients with MMET to determine the predictors of survival. RESULTS:Patients with MMET were more likely to have localized stage disease compared to those with SET (P < 0.0001). Distant stage disease for both first tumor (β = -0.402, P = 0.003) and second tumor (β = -0.301, P = 0.033) were predictors of increased mortality. The interval between the first and second tumor affected survival. Intervals of 2-5 years and > 5 years were associated with a reduced hazard with a β = 0.53 and 1.13, P < 0.0001, respectively. CONCLUSION:Early development of a second tumor in MMET is associated with poorer survival. Patients with MMET may benefit from regular follow-up and intervention to prevent the development of a second tumor.

 Obstructive sleep apnea (OSA) and Alzheimer's disease (AD) are highly prevalent conditions with growing impact on our aging society. While the causes of OSA are now better characterized, the mechanisms underlying AD are still largely unknown, challenging the development of effective treatments. Cognitive impairment, especially affecting attention and executive functions, is a recognized clinical consequence of OSA. A deeper contribution of OSA to AD pathogenesis is now gaining support from several lines of research. OSA is intrinsically associated with disruptions of sleep architecture, intermittent hypoxia and oxidative stress, intrathoracic and hemodynamic changes as well as cardiovascular comorbidities. All of these could increase the risk for AD, rendering OSA as a potential modifiable target for AD prevention. Evidence supporting the relevance of each of these mechanisms for AD risk, as well as a possible effect of AD in OSA expression, will be explored in this review.

The social environment influences health outcomes for older adults and could be an important target for interventions to reduce costly medical care. We sought to understand which elements of the social environment distinguish communities that achieve lower health care utilization and costs from communities that experience higher health care utilization and costs for older adults with complex needs. We used a sequential explanatory mixed methods approach. We classified community performance based on three outcomes: rate of hospitalizations for ambulatory care sensitive conditions, all-cause risk-standardized hospital readmission rates, and Medicare spending per beneficiary. We conducted in-depth interviews with key informants (N = 245) from organizations providing health or social services. Higher performing communities were distinguished by several aspects of social environment, and these features were lacking in lower performing communities: 1) strong informal support networks; 2) partnerships between faith-based organizations and health care and social service organizations; and 3) grassroots organizing and advocacy efforts. Higher performing communities share similar social environmental features that complement the work of health care and social service organizations. Many of the supportive features and programs identified in the higher performing communities were developed locally and with limited governmental funding, providing opportunities for improvement.

INTRODUCTION/BACKGROUND:Link4Health, a cluster-RCT, demonstrated the effectiveness of a combination strategy targeting barriers at various HIV continuum steps on linkage to and retention in care; showing effectiveness in achieving linkage to HIV care within 1 month plus retention in care at 12 months after HIV testing for people living with HIV (RR 1.48, 95% CI 1.19-1.96, p = 0.002). In addition to standard of care, Link4Health included: 1) Point-of-care CD4+ count testing; 2) Accelerated ART initiation; 3) Mobile phone appointment reminders; 4) Care and prevention package including commodities and informational materials; and 5) Non-cash financial incentive. Our objective was to evaluate the cost-effectiveness of a scale-up of the Link4Health strategy in Swaziland. METHODS AND FINDINGS/RESULTS:We incorporated the effects and costs of the Link4Health strategy into a computer simulation of the HIV epidemic in Swaziland, comparing a scenario where the strategy was scaled up to a scenario with no implementation. The simulation combined a deterministic compartmental model of HIV transmission with a stochastic microsimulation of HIV progression calibrated to Swaziland epidemiological data. It incorporated downstream health costs potentially saved and infections potentially prevented by improved linkage and treatment adherence. We assessed the incremental cost-effectiveness ratio of Link4Health compared to standard care from a health sector perspective reported in US$2015, a time horizon of 20 years, and a discount rate of 3% in accordance with WHO guidelines.[1] Our results suggest that scale-up of the Link4Health strategy would reduce new HIV infections over 20 years by 11,059 infections, a 7% reduction from the projected 169,019 cases and prevent 5,313 deaths, an 11% reduction from the projected 49,582 deaths. Link4Health resulted in an incremental cost per infection prevented of $13,310 and an incremental cost per QALY gained of $3,560/QALY from the health sector perspective. CONCLUSIONS:Using a threshold of <3 x per capita GDP, the Link4Health strategy is likely to be a cost-effective strategy for responding to the HIV epidemic in Swaziland.

BACKGROUND:School meals have the potential to improve diet quality for millions of students across the United States. OBJECTIVES:Evaluate the feasibility of the FAV5 program, which aims to strengthen school meals by increasing appeal of school meals and improving relationships within the team of child nutrition staff and with other staff/teachers at their schools. METHODS:Nutrition researchers facilitated partnerships between the following groups to develop and implement the FAV5 program: the child nutrition director (CND) and managers at seven elementary schools in a North Carolina county, teachers and principals at those schools, a chef, the North Carolina Department of Agriculture, and volunteers. RESULTS:The partnerships developed through the FAV5 program produced successful taste test events in seven elementary schools that generated enthusiasm around the school meals program and strengthened relationships. CONCLUSIONS:Engaging child nutrition staff and other community partners to plan and implement the FAV5 program in schools is feasible.

Alcohol, marijuana, and ecstasy (3,4-methylenedioxymethamphetamine [MDMA], 'Molly') are among the most prevalent substances used by young adults; however, few studies have focused on the specific sexual effects associated with use. Examining subjective sexual effects (e.g. increased libido) associated with use can inform prevention efforts. Data were analysed from 679 nightclub and dance festival attendees in New York City (ages 18-25) to examine and compare self-reported sexual effects associated with use of alcohol, marijuana, and ecstasy. Results suggest that compared to marijuana, alcohol and ecstasy were more strongly associated with heightened perceived sexual effects (i.e. perceived sexual attractiveness of self and others, sexual desire, length of intercourse, and sexual outgoingness). Increased body and sex organ sensitivity and increased sexual intensity were most commonly associated with ecstasy use. Sexual dysfunction was most common while using alcohol or ecstasy, especially among males, and females were more likely to report sexual dysfunction after using marijuana. Post-sex regret was most common with alcohol use. Alcohol, marijuana, and ecstasy each have different sexual effects; therefore, each is associated with different risks and benefits for users. Findings can inform prevention and harm reduction as young adults are prone to use these substances.

Prenatal arsenic exposure is associated with adverse birth outcomes and disease risk later in life, which could be mediated through epigenetic dysregulation. We evaluated the association between arsenic and gestational age (GA) that was mediated through DNA methylation (DNAm) using data from a Bangladeshi birth cohort. Arsenic exposure was measured in maternal drinking water at ≤16 weeks GA and maternal toenails collected ≤1 month postpartum. Cord blood DNAm was measured using Infinium HumanMethylation450 arrays (n = 44, discovery phase). Top loci identified in the discovery phase were then pyrosequenced in a second group (n = 569, validation phase). Structural equation models (SEM) evaluated the direct and indirect effects of arsenic and DNAm on GA. In the discovery phase, arsenic was associated with differential DNAm of 139 loci that were associated with GA (P < 1.10X10^-6; |β regression|>0.10). Each doubling in water arsenic concentration decreased GA by 2 days, which was fully mediated through the main principal component of the top-ten CpGs (P < 0.001). In the validation phase, there were direct and indirect effects of miR214-3 and MCC DNAm on GA. In an adjusted SEM model, mediation of the association between arsenic and GA by miR124-3 was borderline significant (P = 0.061). This study therefore identified DNAm at specific loci in cord blood that mediated the effect of arsenic exposure on GA. Specifically, prenatal arsenic exposure was associated with lower methylation of miR124-3 that mediated the exposure-response of arsenic on GA. Future research should evaluate if these epigenetic changes are persistent and associated with disease risk.