Faculty Bibliography

IMPORTANCE:Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations. OBJECTIVE:To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder. DESIGN, SETTING, AND PARTICIPANTS:This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder. INTERVENTIONS:Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group). MAIN OUTCOMES AND MEASURES:Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority. RESULTS:A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group. CONCLUSIONS AND RELEVANCE:Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02651584.

Context/UNASSIGNED:HIV-infected individuals demonstrate unique RAAS physiology, with increased RAAS activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically-based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV. Objective/UNASSIGNED:To investigate effects of eplerenone on insulin sensitivity, inflammatory indices and other metabolic parameters in HIV. Design/UNASSIGNED:Six month, double-blind, randomized, placebo-controlled trial. Setting/UNASSIGNED:Academic clinical research center. Participants/UNASSIGNED:HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis. Intervention/UNASSIGNED:Eplerenone 50mg or placebo daily. Outcome/UNASSIGNED:The primary endpoint was change in insulin stimulated glucose uptake normalized to insulin and lean body mass (M/I/LBM) measured by the euglycemic hyperinsulinemic clamp technique. Secondary endpoints included change in body composition and markers of inflammation. Results/UNASSIGNED:Forty-six individuals were randomized to eplerenone (n=25) vs. placebo (n=21). Eplerenone did not improve insulin sensitivity [M/I/LBM (0.48 [-1.28,1.48] vs. 0.43 [-1.95,2.55] mg/min per μIU/mL, P=0.71, eplerenone vs. placebo) when measured by the gold standard euglycemic hyperinsulinemic clamp technique. IMCL (P=0.04), MCP-1(P=0.04), and HDL (P=0.04) improved among those randomized to eplerenone vs. placebo. Trends toward decreases in IL-6 (P=0.10) and hsCRP (P=0.10) were also seen with eplerenone vs. placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs. placebo-treated group demonstrating expected physiology. MR antagonism with eplerenone was well-tolerated among the HIV population with no significant changes in blood pressure or potassium. Conclusion/UNASSIGNED:MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.

BACKGROUND:The near-universal prevalence of electronic health records (EHRs) has made the utilization of clinical decision support systems (CDSS) an integral strategy for improving the value of laboratory ordering. Few studies have examined the effectiveness of nonintrusive CDSS on inpatient laboratory utilization in large academic centres. METHODS:Red blood cell folate, hepatitis C virus viral loads and genotypes, and type and screens were selected for study. We incorporated the appropriate indications for these labs into text that accompanied the laboratory orders in our hospital's EHR. Providers could proceed with the order without additional clicks. An interrupted time-series analysis was performed, and the primary outcome was the rate of tests ordered on all inpatient medicine floors. RESULTS:The rate of folate tests ordered per monthly admissions showed no significant level change at the time of the intervention with only a slight decrease in rate of 0.0109 (P = .07). There was a 43% decrease in the rate of hepatitis C virus tests per monthly admissions immediately after the intervention with a decrease of 0.0135 tests per monthly admissions (P = .02). The rate of type and screens orders per patient days each month had a significant downward trend by 0.114 before the intervention (P = .04) but no significant level change at the time of the intervention or significant change in rate after the intervention. DISCUSSION/CONCLUSIONS:Our study suggests that nonintrusive CDSS should be evaluated for individual laboratory tests to ensure only effective alerts continue to be used so as to avoid increasing EHR fatigue.

Aim: Naltrexone is first-line pharmacotherapy for alcohol use disorders (AUD). Oral naltrexone (ONTX) is under-prescribed in primary care and possibly limited by poor adherence. Monthly injectable extended-release naltrexone (XR-NTX) may improve rates of medication adherence, retention, good clinical outcomes (Aim 1), and cost savings (Aim 2). Methods: This is an on-going randomized, open-label, comparative effectiveness trial of 24 weeks of XR-NTX vs. O-NTX as AUD treatment in primary care at a public hospital in New York City. Adults (>18 yo) with a DSM-V diagnosis of AUD randomized to XR-NTX (380 mg/month) vs. O-NTX (50-100 mg/day).Medical Management visits occur biweekly (weeks 1-8), then monthly.Major research assessments occur at baseline, weeks 13, 25, 48. The primary outcome is a Good Clinical Outcome (GCO) across weeks 5-24: abstinence or moderate drinking and 0-2 days of heavy drinking per month. This preliminary, descriptive analysis presentsWeek 0-5 results among all participants. Results: N = 237 participants were randomized from 6/14-9/17: mean age 48.5 (SD = 10.6); 71% male; 54% AA, 21%Hispanic; 41% employed, 81%reported other lifetime substance use. Mean AUDIT scores (instrument range 0-40) at baseline: 24.2 (SD = 8.0); mean OCDS (range 0-40) scores 17.1 (SD = 8.1); mean drinks/day 9.6 (SD = 11.6) with 29%abstinent vs. 61% heavy drinking days. Medication induction was robust, 115 of 117 (98.2%) initiating XR-NTX and 120 (100%) filled or received an initial O-NTX prescription. The GCO was reported by 41%XR-NTX and 47%ONTX atWeek 5. DuringWeek 1-5, mean drinks/day were 3.1 (SD = 6.1), 63% abstinent/22%heavy drinking days for XR-NTX; 2.4 (SD = 4.03), 61%abstinent/22%heavy drinking days for O-NTX. 62%received XR-NTX injection #2 and 67%received O-NTXmonthly refill #2. Adherence self-report for O-NTX at Week 5 indicated moderate average daily adherence,MMAS-8 mean (range <6 low, 6 to <8 moderate, =8 high) score 6.13 (SD = 3.02). Conclusion: This on-going XR vs. oral naltrexone alcohol primary care treatment trial recruited a primarily male, unemployed, ethnic minority adult population. Initial acceptance of both XR and ONTX was high. Primary outcomes will focus on drinking reductions and cost and value comparisons during weeks 5-24

BACKGROUND:Two dominant themes face medical education: developing integrated curricula and improving the undergraduate medical education (UME) to graduate medical education (GME) transition. An innovative solution to both of these challenges at the Zucker School of Medicine has been the application of the cognitive apprenticeship framework in requiring emergency medical technician (EMT) certification during the first course in medical school as the core on which to build an integrated curriculum and provide entrustable clinical skills. METHODS:Beginning with the Class of 2011, student feedback about the short-term impact of the experience was collected annually. In addition, perceptions of near graduates and alumni were surveyed in 2017 to explore the long-term impact of the experience. Theme analysis was conducted via inductive coding. RESULTS:Both first-year and more experienced learners report the value of the EMT curriculum as an integrated component of the first course of medical school. Reported positive long-term impacts included the first-hand observation of social determinants of health and interprofessionalism. Negative comments by early learners focused on course logistics, whereas older learners recalled the variability of clinical experiences during ambulance runs. CONCLUSIONS:The integration of the EMT curriculum as a core component of the first course serves multiple purposes: 1) it provides the foundation of a spiral learning approach; 2) it contextualizes the basic sciences within clinical practice; 3) it provides opportunities for students to engage in authentic clinical activities under the guidance of mentors; 4) it introduces students to the interdisciplinary nature of medicine; and 5) it serves as the first entrustable professional activity (EPA) for our students.

BACKGROUND:Portal vein thrombosis (PVT) develops in cirrhotic patients because of stagnation of blood flow. Transjugular intrahepatic portosystemic shunt (TIPS) creates a low-resistance conduit that restores portal venous patency and blood flow. AIM/OBJECTIVE:The effect of PVT on transplant-free survival in cirrhotic patients undergoing TIPS creation was evaluated. PATIENTS AND METHODS/METHODS:A multicenter, retrospective cohort study of patients who underwent TIPS creation for cirrhotic portal hypertension was carried out. A Cox model with propensity score adjustment was developed to evaluate the effect of PVT on 90-day and 3-year transplant-free survival. A subgroup analysis examining mortality of those with superior and distal PVT was also carried out. RESULTS:A total of 252 consecutive TIPS creations were assessed, including 65 in patients with PVT. Survival of patients with high Model for End-stage Liver Disease scores (≥18) and PVT was not statistically different compared with patients with low Model for End-stage Liver Disease scores (<18) and no PVT at 90 days (P=0.46) and 3 years (P=0.42). Those with inferior PVT had improved 90-day and 3-year survival both compared with patients with a superior PVT and those without a PVT (P<0.01, all cases). CONCLUSION/CONCLUSIONS:The presence of PVT does not impair the prognosis of patients following TIPS creation, particularly in patients with distal portal occlusion.