Faculty Bibliography

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.

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.

Introduction/UNASSIGNED:Research staff are critical to productive translational research teams, yet their professional development is rarely formally addressed. Methods/UNASSIGNED:We created Strategic Teamwork for Effective Practice Mentor Development Program (STEP-MDP) to promote skills development and build a community of practice. We ran and evaluated the STEP-MDP for 32 participants, which consisted of workshops focusing on team communication and mentorship/coaching skills. Results/UNASSIGNED:We found that STEP-MDP had a long-term positive impact on participants and their teams. Conclusion/UNASSIGNED:This program facilitated the professional development of research staff.

BACKGROUND:Patient-centered medical homes have made great strides providing comprehensive care for patients with chronic conditions, but may not provide sufficient support for patients at highest risk for acute care use. To address this, the Veterans Health Administration (VHA) initiated a five-site demonstration project to evaluate the effectiveness of augmenting the VA's Patient Aligned Care Team (PACT) medical home with PACT Intensive Management (PIM) teams for Veterans at highest risk for hospitalization. METHODS/DESIGN/METHODS:Researchers partnered with VHA leadership to design a mixed-methods prospective multi-site evaluation that met leadership's desire for a rigorous evaluation conducted as quality improvement rather than research. We conducted a randomized QI evaluation and assigned high-risk patients to participate in PIM and compared them with high-risk Veterans receiving usual care through PACT. The summative evaluation examines whether PIM: 1) decreases VHA emergency department and hospital use; 2) increases satisfaction with VHA care; 3) decreases provider burnout; and 4) generates positive returns on investment. The formative evaluation aims to support improved care for high-risk patients at demonstration sites and to inform future initiatives for high-risk patients. The evaluation was reviewed by representatives from the VHA Office of Research and Development and the Office of Research Oversight and met criteria for quality improvement. DISCUSSION/CONCLUSIONS:VHA aims to function as a learning organization by rapidly implementing and rigorously testing QI innovations prior to final program or policy development. We observed challenges and opportunities in designing an evaluation consistent with QI standards and operations priorities, while also maintaining scientific rigor. TRIAL REGISTRATION/BACKGROUND:This trial was retrospectively registered at ClinicalTrials.gov on April 3, 2017: NCT03100526. Protocol v1, FY14-17.

OBJECTIVES:The care cascade, a method for tracking population-level progression from diagnosis to cure, is an important tool in addressing and monitoring the hepatitis C virus (HCV) epidemic. However, little agreement exists on appropriate care cascade steps or how best to measure them. The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) sought to construct a care cascade by using laboratory surveillance data with clinically relevant categories that can be readily updated over time. METHODS:We identified all NYC residents ever reported to the DOHMH surveillance registry with HCV through June 30, 2017 (n = 175 896). To account for outmigration, death, or treatment before negative RNA results became reportable to the health department, we limited the population to people with any test reported since July 1, 2014. Of these residents, we identified the proportion with a reported positive RNA test and estimated the proportion treated and cured since July 2014 by using DOHMH-developed surveillance-based algorithms. RESULTS:Of 78 886 NYC residents ever receiving a diagnosis of HCV and tested since July 1, 2014, a total of 70 397 (89.2%) had ever been reported as RNA positive through June 30, 2017; 36 875 (46.7%) had initiated treatment since July 1, 2014, and 23 766 (30.1%) appeared cured during the same period. CONCLUSION:A substantial gap exists between confirming HCV infection and initiating treatment, even in the era of direct-acting antivirals. Using this cascade, we will monitor progress in improved treatment and cure of HCV in NYC.

An excerpt from Dr. Peter Berczeller's memoir, "The Little White Coat"

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.

Background /UNASSIGNED:Physicians across specialties need to be skilled at diagnosing and treating depression, yet studies show underrecognition and inadequate treatment. Understanding the reasons requires specifying the influence of patient presentation, screening, and physician competence. Objective /UNASSIGNED:We deployed an unannounced standardized patient (SP) case to assess clinic screening and internal medicine (IM) residents' practices in identifying, documenting, and treating depression. Methods /UNASSIGNED:The SP represented a new patient presenting to the outpatient clinic, complaining of fatigue, with positive Patient Health Questionnaire (PHQ) items 2 and 9 and a family history of depression. The SPs assessed clinic screening and IM resident practices; appropriate treatment was assessed through chart review and defined as the resident doing at least 1 of the following: prescribing a selective serotonin reuptake inhibitor (SSRI), making a referral, or scheduling a 2-week follow-up. Results /UNASSIGNED:< .001). Conclusions /UNASSIGNED:The use of unannounced SPs helps identify targets for training residents to provide evidence-based treatment of depression.