Faculty Bibliography

More than 37 million people are living with human immunodeficiency virus 1 (HIV), and more people than ever received lifesaving antiretroviral therapy worldwide. HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the GI microbiome and its association with host immune activation. The data indicated that the microbiome was different in HIV-positive and HIV-negative individuals. The initial sequence analysis of saliva indicated that there were major differences in the phyla of Bacteroidetes, Firmicutes, Proteobacteria, and TM7. Phylum Tenericutes was only seen in HIV-positive saliva. At the family level, we identified differences in Streptococcacea, Prevotellaceae, Porphyromonadaceae, and Neisseriaceae, whereas data from various sites in GI tract indicated that Prevotella melaninigencia, Fusobacterium necrophorum, Burkholderia, Bradyrhizobium, Ralstonia, and Eubacterium biforme were predominant but differentially present at various sites. Furthermore, there was a decrease in seven proteins associated with the alternative complement pathway and an increase in 6 proteins associated with the lectin and classical complement pathways. The correlation with a shift in complement pathways suggests that compromised immunity could be responsible for the observed dysbiosis in the GI microbiome.

STUDY OBJECTIVE: In 2006, the Institute of Medicine emphasized substantial potential to expand organ donation opportunities through uncontrolled donation after circulatory determination of death (uDCDD). We pilot an out-of-hospital uDCDD kidney program for New York City in partnership with communities that it was intended to benefit. We evaluate protocol process and outcomes while identifying barriers to success and means for improvement. METHODS: We conducted a prospective, participatory action research study in Manhattan from December 2010 to May 2011. Daily from 4 to 12 pm, our organ preservation unit monitored emergency medical services (EMS) frequencies for cardiac arrests occurring in private locations. After EMS providers independently ordered termination of resuscitation, organ preservation unit staff determined clinical eligibility and donor status. Authorized parties, persons authorized to make organ donation decisions, were approached about in vivo preservation. The study population included organ preservation unit staff, authorized parties, passersby, and other New York City agency personnel. Organ preservation unit staff independently documented shift activities with daily operations notes and teleconference summaries that we analyzed with mixed qualitative and quantitative methods. RESULTS: The organ preservation unit entered 9 private locations; all the deceased lacked previous registration, although 4 met clinical screening eligibility. No kidneys were recovered. We collected 837 notes from 35 organ preservation unit staff. Despite frequently recounting protocol breaches, most responses from passersby including New York City agencies were favorable. No authorized parties were offended by preservation requests, yielding a Bayesian posterior median 98% (95% credible interval 76% to 100%). CONCLUSION: In summary, the New York City out-of-hospital uDCDD program was not feasible. There were frequent protocol breaches and confusion in determining clinical eligibility. In the small sample of authorized persons we encountered during the immediate grieving period, negative reactions were infrequent.

OBJECTIVE: To examine the cost and cost-effectiveness of implementing Students for Nutrition and eXercise (SNaX), a 5-week middle school-based obesity-prevention intervention combining school-wide environmental changes, multimedia, encouragement to eat healthy school cafeteria foods, and peer-led education. METHODS: Five intervention and 5 control middle schools (mean enrollment, 1520 students) from the Los Angeles Unified School District participated in a randomized controlled trial of SNaX. Acquisition costs for materials and time and wage data for employees involved in implementing the program were used to estimate fixed and variable costs. Cost-effectiveness was determined using the ratio of variable costs to program efficacy outcomes. RESULTS: The costs of implementing the program over 5 weeks were $5433.26 per school in fixed costs and $2.11 per student in variable costs, equaling a total cost of $8637.17 per school, or $0.23 per student per day. This investment yielded significant increases in the proportion of students served fruit and lunch and a significant decrease in the proportion of students buying snacks. The cost-effectiveness of the program, per student over 5 weeks, was $1.20 per additional fruit served during meals, $8.43 per additional full-priced lunch served, $2.11 per additional reduced-price/free lunch served, and $1.69 per reduction in snacks sold. CONCLUSIONS: SNaX demonstrated the feasibility and cost-effectiveness of a middle school-based obesity-prevention intervention combining school-wide environmental changes, multimedia, encouragement to eat healthy school cafeteria foods, and peer-led education. Its cost is modest and unlikely to be a significant barrier to adoption for many schools considering its implementation.

We estimated the economic costs of female reproductive disorders attributable to endocrine disrupting chemical exposures. These may contribute substantially to fibroids and endometriosis, costing nearly euro1.5 billion annually.

PURPOSE: Correctional settings create unique challenges for patients with special needs, including transgender patients, who have an increased rate of overall discrimination, sexual abuse, healthcare disparities, and improper housing. As part of our correctional health quality improvement process, we sought to review and evaluate the adequacy of care for transgender patients in the New York City jail system. METHODS: Using correctional pharmacy records, transgender patients receiving hormonal treatment were identified. A brief in-person survey was conducted to evaluate their care in the community before incarceration, medical care in jail, and experience in the jail environment. RESULTS: Survey findings and analysis of transgender patient healthcare-related complaints revealed opportunities for improvements in the provision of care and staff understanding of this population. Utilizing these findings, we conducted lesbian, gay, bisexual, and transgender (LGBT) trainings in all 12 jail clinics for medical, nursing, and mental health staff. Three months after LGBT training, patient complaints dropped by over 50%. After the development and implementation of a newly revised transgender healthcare policy, complaints dropped to zero within 6 months. CONCLUSION: Our efforts to assess the quality of care provided to transgender patients revealed significant areas for improvement. Although we have made important gains in providing quality care through the implementation of policies and procedures rooted in community standards and the express wishes of our patients, we continue to engage this patient population to identify other issues that impact their health and well-being in the jail environment.

OBJECTIVE: To determine range of bottle sizes used and examine the relationship between bottle size and total daily consumption of infant formula. METHODS: Cross-sectional analysis of baseline data collected as part of Greenlight, a cluster randomized trial to prevent childhood obesity at 4 pediatric resident clinics. The Greenlight study included healthy, term infants. For our analysis, parents of exclusively formula-fed infants reported volume per feed, number of feeds per day, and bottle size, which was dichotomized into small (<6 oz) or large (>/=6 oz). We identified determinants of bottle size, and then examined relationships between bottle size and volume fed with log-transformed ordinary least squares regression, adjusting for infant age, sex, birth weight, current weight, race/ethnicity, and enrollment in Special Supplemental Nutrition Program for Women, Infants, and Children. RESULTS: Of 865 participants in the Greenlight study, 44% (n = 378; 21.8% white, 40.6% black, 35.3% Hispanic, 2.4% other) of infants were exclusively formula fed at 2 months. Median volume per day was 30 oz (interquartile range 12), and 46.0% of infants were fed with large bottles. Adjusted for covariates, parents using larger bottles reported feeding 4 oz more formula per day (34.2 oz, 95% confidence interval 33.5-34.9 vs 29.7 oz, 95% confidence interval 29.2-30.3, P = .03). CONCLUSIONS: Among exclusively formula-fed infants, use of a larger bottle is associated with parental report of more formula intake compared to infants fed with smaller bottles. If infants fed with larger bottles receive more formula, these infants may be overfed and consequently at risk for obesity.

A goal of aspirin therapy is to inhibit thromboxane production and platelet aggregation without inhibiting endothelial production of the vasodilator and anti-thrombotic prostacyclin. This study tested the hypothesis that extended-release aspirin (NHP-554C) would have increased selectivity for inhibition of basal and simulated thromboxane formation compared to immediate-release aspirin (ASA). Thirty-six healthy subjects were randomized to NHP-554C or ASA groups. Within each group, subjects were randomized to 5-day treatment with 81 mg/d, 162.5 mg/d and placebo in a crossover design in which treatment periods were separated by 2-week washout. On the fifth day of treatment, 81 mg/d and 162.5 mg/d ASA reduced basal urinary excretion of the stable thromboxane metabolite 11-dehydro-thromboxane B2 62.3% and 66.2% and basal excretion of the stable prostacyclin metabolite 2,3-dinor-6-keto-PGF1α 22.8% and 26.5%, respectively, compared to placebo. NHP-554C 81 mg/d and 162.5 mg/d reduced 11-dehydro-thromboxane B2 53% (P = 0.03 vs. ASA 81 mg/d) and 67.9% and 2,3-dinor-6-keto-PGF1α 13.4% and 18.5%, respectively. NHP-554C 81 mg/d did not significantly reduce basal excretion of the prostacyclin metabolite. Both doses of ASA and NHP significantly reduced excretion of both thromboxane and prostacyclin metabolites following intravenous bradykinin. During NHP-554C 162.5 mg/d, but not during ASA, bradykinin significantly increased urinary 2,3-dinor-6-keto-PGF1α. Nevertheless, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-PGF1α responses to bradykinin were statistically similar during ASA and NHP-554C. In conclusion, at doses of 81 and 162.5 mg/d immediate- and extended-release aspirin selectively decrease basal thromboxane production. Both forms of aspirin decrease bradykinin-stimulated thromboxane and prostacyclin production, but some stimulated prostacyclin production remains during treatment with NHP-554C.

BACKGROUND: Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS: In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS: A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS: In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).