The study uses a Hybrid Type 3 Effectiveness-Implementation framework and a modified stepped wedge design. The study will be conducted at four EDs with a high prevalence of patients with untreated opioid use disorder (OUD). The four sites will receive the same sequence of evaluations and interventions: the baseline evaluation period after the standard dissemination practice, the IF phase, and continuation of facilitation into the IF evaluation period. The timing of initiation of the study activities at each site will be randomly offset by ~ 3 month increments to accommodate logistical constraints of simultaneous implementation at all sites. The study populations will include (1) ED providers and staff involved in the treatment of patients with OUD; (2) Community opioid treatment provider and program staff involved in providing care for patients with OUD referred from the ED; and (3) ED patients with moderate to severe OUD.

This study compares two methods of initiating treatment with extended-release naltrexone (XR-NTX) when implemented at community-based inpatient or residential programs. The primary goal of this hybrid effectiveness-implementation study is to determine whether the Rapid method of initiating treatment with XR-NTX is non-inferior to a standard method on the primary effectiveness outcome of successful initiation of XR-NTX (receiving the first injection while inpatient) when implemented at community-based inpatient or residential programs. Secondary objectives include comparing rapid versus standard method of XR-NTX initiation on: time from admission to first dose of XR-NTX while inpatient and time to dropout, craving, withdrawal severity, retention, abstinence, and safety measures.

The goal of the project is to build a clinical data research infrastructure that will begin to enhance capacity to use electronic health record (EHR) data and patient reported outcomes measures (PROs) to conduct opioid related research in emergency departments (EDs). 200 adult patients with a history of non-medical opioid use, opioid use disorder, or acute opioid overdose will be enrolled and will be asked to complete three PRO surveys (baseline, 3 days post ED discharge, and 30 days post discharge).

The aims of this study are: 1. To evaluate using mixed methods the feasibility and acceptability of OUD screening, ED-initiated BUP, and referral. 2. Over the course of the study and as XR-BUP is added to hospital formularies, to estimate the percentage and confidence intervals of patients assessed, treated, and engaged in treatment at Day 30. This will be a three-site study employing a multi-faceted approach to facilitate clinical protocol implementation and to assess feasibility, acceptability, and impact. Investigators will develop, introduce and update site-specific ED clinical protocols and implementation plans for OUD screening, ED-initiated BUP, and referral for treatment. A participatory action research approach will be utilized along with mixed methods incorporating data derived from: Medical record and administrative data abstraction; Research assessments involving patients who are eligible for and willing to receive ED-initiated BUP (including both those who do, and do not, receive BUP); Qualitative interviews, focus groups, and quantitative assessments involving providers and staff, patients, and other stakeholders.

CTN 0064 has two main components: Component 1 is the baseline assessment for CTN 0064. It will also serve as a long-term follow-up assessment for CTN 0049 for those who consent to participate in CTN 0064. Participants whose HCV antibody test result is positive in this baseline assessment will be invited to enroll in Component 2. Component 2 is an RCT that will assess the effectiveness of a Care Facilitation intervention (compared to Control) in moving HIV/HCV co-infected substance users forward along the HCV care continuum. The study's primary objective is based on Component 2 and will be operationalized as movement through a series of (potentially non-sequential) pre-defined, clinical steps along the HCV care continuum (including the ultimate step, sustained virologic response to treatment at 12 weeks post treatment completion [SVR12]) (AASLD/IDSA/IAS-USA). Secondary objectives will be to assess: 1) success at each step in the HCV care continuum, 2) engagement in HIV care and substance use treatment, and 3) HIV viral suppression as well as 4) to examine other long-term outcomes of the CTN 0049 cohort.

This is a 19-week, multi-center, parallel group study that includes: 1) up to 3 weeks for screening; 2) a 13-week Treatment Phase consisting of a 1-week, single-blind run-in period, when all subjects receive twice daily 15 mg acetazolamide capsules (a medication adherence marker), followed by randomization to either twice daily 10 mg lorcaserin or placebo capsules for the remaining 12 weeks; and 3) a 3-week follow-up period, with scheduled visits during Study Weeks 14 and 16.