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.

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.

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time.

OBJECTIVE:Hypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS). METHODS:Data from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed. RESULTS:At baseline, HRQoL did not differ between PIT-CS (n = 293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 41 ± 18 and 44 ± 20, respectively (P = .7). At long-time follow-up (>1 year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 ± 20 vs 62 ± 23; P = .045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P < .001), and older age at diagnosis with worse total score (P = .01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P < .001). CONCLUSION:PIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.

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.