Faculty Bibliography

BACKGROUND:Hepatocellular carcinoma (HCC) is a complication of chronic hepatitis B and C virus (HBV and HCV) infection. New York City (NYC) has a high prevalence of HBV and HCV, and infected persons likely face increased mortality from HCC and other causes. We describe the mortality profile of NYC residents with HBV or HCV, emphasizing the contributions of HCC and HIV coinfection. METHODS: Two existing data sets were combined to examine all individuals diagnosed with HBV or HCV in NYC first reported to the Health Department during 2001-2012 and their HCC, HIV, and vital status. Logistic regression was used to calculate the odds of HCC diagnosis by viral hepatitis status, whereas Cox proportional hazard regression was used to estimate the hazard of death by HCC/HIV status. RESULTS:In total, 120 952 and 127 933 individuals were diagnosed with HBV or HCV, respectively. HCV-infected individuals had 17% higher odds of HCC diagnosis than HBV-infected individuals and 3.2 times higher odds of HIV coinfection. Those with HCV were twice as likely to die during the study period (adjusted hazard ratio, 2.04; 95% confidence interval, 1.96-2.12). The risk of death increased for those with HIV or HCC and was highest for those with both conditions. CONCLUSIONS:HCC and HIV represent substantial risks to survival for both HBV- and HCV-infected individuals. Individuals with HBV need close monitoring and treatment, when indicated, and routine HCC screening. Those with HCV need increased, timely access to curative medications before developing liver disease.

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24-months and allograft histology score at 12-month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24-months posttransplant, and at last follow-up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12-months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor-specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long-term implications for kidney allograft function.

OBJECTIVES/OBJECTIVE:The National Patient-Centered Clinical Research Network (PCORnet) supports observational and clinical research using healthcare data. The PCORnet Antibiotics and Childhood Growth Study is one of PCORnet's inaugural observational studies. The objectives of this manuscript are to describe (1) the processes used to integrate and analyze data from children across 36 participating institutions and (2) the cohort characteristics and prevalence of antibiotic use. METHODS:percentile. RESULTS:681,739 children met the cohort inclusion criteria and were racially/ethnically diverse (24.9% black, 17.5% Hispanic). Before 24 months, 55.2% of children received at least one antibiotic prescription; 21.3% received a single antibiotic prescription, 14.3% received four or more, and 33.3% received a broad spectrum antibiotic. Overweight and obesity prevalence was 27.6% at 4 to <6 years of age (n=362,044) and 36.2% at 9 to <11 years (n=58,344). CONCLUSION/CONCLUSIONS:The PCORnet Antibiotics study is a large, national longitudinal observational study in a diverse population that will examine the relationship between early antibiotic use and subsequent growth patterns in children.

Background/UNASSIGNED:Primary care models that offer comprehensive, accessible care to all patients may provide insufficient resources to meet the needs of patients with complex conditions who have the greatest risk for hospitalization. Objective/UNASSIGNED:To assess whether augmenting usual primary care with team-based intensive management lowers utilization and costs for high-risk patients. Design/UNASSIGNED:Randomized quality improvement trial. (ClinicalTrials.gov: NCT03100526). Setting/UNASSIGNED:5 U.S. Department of Veterans Affairs (VA) medical centers. Patients/UNASSIGNED:Primary care patients at high risk for hospitalization who had a recent acute care episode. Intervention/UNASSIGNED:Locally tailored intensive management programs providing care coordination, goals assessment, health coaching, medication reconciliation, and home visits through an interdisciplinary team, including a physician or nurse practitioner, a nurse, and psychosocial experts. Measurements/UNASSIGNED:Utilization and costs (including intensive management program expenses) 12 months before and after randomization. Results/UNASSIGNED:2210 patients were randomly assigned, 1105 to intensive management and 1105 to usual care. Patients had a mean age of 63 years and an average of 7 chronic conditions; 90% were men. Of the patients assigned to intensive management, 487 (44%) received intensive outpatient care (that is, ≥3 encounters in person or by telephone) and 204 (18%) received limited intervention. From the pre- to postrandomization periods, mean inpatient costs decreased more for the intensive management than the usual care group (-$2164 [95% CI, -$7916 to $3587]). Outpatient costs increased more for the intensive management than the usual care group ($2636 [CI, $524 to $4748]), driven by greater use of primary care, home care, telephone care, and telehealth. Mean total costs were similar in the 2 groups before and after randomization. Limitations/UNASSIGNED:Sites took up to several months to contact eligible patients, limiting the time between treatment and outcome assessment. Only VA costs were assessed. Conclusion/UNASSIGNED:High-risk patients with access to an intensive management program received more outpatient care with no increase in total costs. Primary Funding Source/UNASSIGNED:Veterans Health Administration Primary Care Services.

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.